WO2012064739A2 - Microbial enrichment primers - Google Patents

Abstract

A primer set, referred to as the Microbial Enrichment Primers (MEP) that generates cDNA libraries depleted of ribosomal and mitochondrial sequences is provided. The primer set is useful in a method that enriches for the presence of microbial nucleic acids from samples. The method enhances sensitivity of microbe detection.

Description

MICROBIAL ENRICHMENT PRIMERS

[0001] This patent disclosure contains material that is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure as it appears in the U.S. Patent and Trademark Office patent file or records, but otherwise reserves any and all copyright rights.

[0002] This invention was made with government support under A 1070411 and Al 057158 awarded by the National Institute of Allergy and Infectious Diseases. The government has certain rights in the invention.

[0003] This application claims the benefit of and priority to U.S. provisional patent application Ser. No. 61/411,142 filed November 8, 2010 and U.S. provisional patent application Ser. No. 61/424,276 filed December 17, 2010, the disclosures of each of which is hereby incorporated by reference in its entirety for all purposes.

BACKGROUND OF THE INVENTION

[0004] Microarrays and unbiased high throughput sequencing of nucleic acid from tissue specimens is greatly impeded by the presence of a large quantity of host RNA, especially ribosomal RNA (rRNA) which accounts for about 90-95% RNA species in total RNA.

[0005] There is a need to devise primer design methods useful for enriching the presence of microbial nucleic acids, and enhancing sensitivity of microarrays and high throughput sequencing analysis. There is also a need to reduce costs associated with the use of such platforms in surveillance, diagnosis and discovery of micro-organisms and other microbes in research and medicine. This invention addresses these needs.

FIELD OF THE INVENTION

[0006] The invention relates to the field of microbe detection. In particular, the invention relates to microbe detection in an organism using transcriptome libraries.

SUMMARY OF THE INVENTION

[0007] It is understood that any of the embodiments described below can be combined in any desired way, and any embodiment or combination of embodiments can be applied to each of the aspects described below. [0008] In one aspect, the invention provides a composition comprising 20 or more nucleic acid sequences, wherein each of the 20 nucleic acid sequence comprises a different hexamer sequence selected from the group consisting of the hexamers sequences in Table 1 , provided that at least one nucleic sequence does not comprise a hexamer sequence selected from the group consisting of the hexamer sequences in Table 4.

[0009] In some embodiment, each different hexamer sequence is selected from the group consisting of the hexamer sequences in Table 2. In some embodiments, each different hexamer sequence is selected from the group consisting of hexamer sequences in Table 3.

[0010] In some embodiments, the composition comprises 200 or more nucleic acid sequences. In some embodiments, the composition comprises 800 or more nucleic acid sequences.

[0011] In some embodiments, each nucleic acid further comprises a tail sequence 5' to the hexamer sequence, wherein the tail sequence is about 10 to about 22 nucleotides in length, wherein tail sequence is separated from the hexamer sequence by 0 to 10 nucleotides, wherein each nucleic acid comprises the same tail sequence.

[0012] In some embodiment, each nucleic acid in the composition has the same length or substantially the same length. In some embodiments, each nucleic acid has the hexamer sequence in the same position in the nucleic acid.

[0013] In some embodiments, each nucleic acid sequence is a primer. In some embodiments, each nucleic sequence is DNA, RNA, PNA, LNA, GNA or TNA.

[0014] In another aspect, the invention provides a method for designing a primer set for amplification of microbial nucleic acids in an organism comprising: (a) sequencing the transcriptome of an organism; (b) identifying highly expressed genes of the organism from the plurality of sequence reads identified in step (a); (c) providing a first primer library, wherein each primer comprises a different hexamer sequence; and (d) removing primers from the first primer library that are predicted to anneal to the RNA of the organism's highly expressed genes to generate a second primer library, provided that primers expected to anneal to the RNA predicted to form a secondary structure are not removed from the first primer library.

[0015] In some embodiment, primers comprising hexamer sequences with perfect sequence matches to the regions giving a substantial number of reads are removed from the first primer library. In some embodiment, the substantial amount of reads is more than 1% of the relative coverage depth.

[0016] In some embodiments, steps (b) or (d) are performed by a computer.

[0017] In some embodiments, the organism's highly expressed genes comprise 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase, NADH dehydrogenase. In some embodiments, the organism's highly expressed genes further comprise one or more additional oxidative phosphorylation genes.

[0018] In some embodiments, the transcriptome of the organisms is sequenced using unbiased high throughput sequencing.

[0019] In some embodiments, the second primer library comprises 20 or more primers. In some embodiments, the second primer library comprises 800 or more primers. In some embodiments, the second primer library comprises 1600 or more primers.

[0020] In some embodiments, the method further comprises separating the primers in the second primer library into two primer sets.

[0021] In some embodiments, one primer set is used to generate a first cDNA strand from total RNA and the other primer set is used to generate a second cDNA strand from the first cDNA strand.

[0022] In some embodiments, the organism is a eukaryote. In some embodiments, the organism is a human.

[0023] In some embodiments, the method further comprises producing the second primer library.

[0024] In another aspect, the invention provides a method for amplifying a microbial nucleic acid comprising: (a) providing a sample from an organism; (b) isolating total RNA from the sample; (c) reverse-transcribing total RNA from the sample using a set of forward strand primers to provide a first cDNA strand, wherein the forward strand primers are designed not to amplify organism's 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase and NADH dehydrogenase RNA transcripts, wherein the forward strand primers comprise primers complementary to regions predicted to form secondary RNA structure of the organism's 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase and NADH dehydrogenase RNA transcripts; (d) replicating the first cDNA strand using a set of reverse strand primers to provide a second cDNA strand, wherein the reverse strand primers comprise primers are designed not to amplify organism's 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase and NADH dehydrogenase RNA transcripts, wherein the reverse strand primers comprise primers complementary to regions predicted to form secondary RNA structure of the organism's 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase and NADH dehydrogenase RNA transcripts; (e) allowing the first and the second cDNA strands to anneal to provide double-stranded cDNA; and (f) amplifying the double stranded cDNA using polymerase chain reaction using double-strand cDNA primers.

[0025] In some embodiments, the forward strand primers and the reverse strand primers are further designed not to amplify the RNA transcripts of one or more additional oxidative phosphorylation genes.

[0026] In some embodiments, the forward strand primers and the reverse strand primers each comprise a different hexamer sequence. In some embodiments, the forward strand primers and the reverse strand primers each comprise the same specific tail sequence.

[0027] In some embodiments, at least one of the double-strand cDNA primers is complementary to the specific tail sequence or a portion thereof.

[0028] In some embodiments, each forward strand primer comprises a hexamer sequence selected from the group consisting of the hexamer sequences in Table 2. In some embodiments, each reverse strand primer comprises a hexamer sequence selected from the group consisting of the hexamer sequences in Table 3.

[0029] In some embodiments, the method further comprises determining whether the organism is infected with a microbe.

[0030] In another aspect, the invention provides a composition comprising 800 or more nucleic acids, wherein each nucleic acid has the structure: H-N_a-ST; wherein H is a nucleotide sequence of 5 to 7 nucleotides; N is a random nucleotide; a is an integer from 0 to 12; and ST is a nucleotide sequence from 10-22 nucleotides, provided that each nucleic acid in the composition has a different sequence H.

[0031] In some embodiments, H is a nucleotide sequence of 6 nucleotides. In some embodiments, in at least one nucleic acid sequence H is not selected from the group consisting of the hexamer sequences in Table 4. [0032] In some embodiments, H is selected from the group consisting of the hexamer sequences in Table 2. In some embodiments, H is selected from the group consisting of the hexamer sequences in Table 3.

[0033] In some embodiments, a is 1. In some embodiments, the composition comprises at least 1600 nucleic acids. In some embodiments, ST is a nucleotide sequence of 17 nucleotides.

[0034] In another aspect, the invention provides a kit comprising a composition of any of the aspects and embodiments described above and instructions for use.

BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Fig. 1 is a schematic of a secondary DNA structure impeding the ability to synthesize cDNA;

[0036] Fig. 2 is an illustration of the coverage depth for the 28S rRNA gene by unbiased 454 high-throughput sequencing;

[0037] Fig. 3A is an illustration of the first strand cDNA synthesis using forward strand microbial enrichment (FS-MEP) primers;

[0038] Fig. 3B is an illustration of the second strand cDNA synthesis using reverse strand microbial enrichment (RS-MEP) primers;

[0039] Fig. 3C is an illustration of the PCR amplification of double stranded cDNA generated with the FS-MEP and RS-MEP primers;

[0040] Figs. 4A and 4B are illustrations explaining coverage depth;

[0041] Fig. 5 is an illustration of the predicted secondary structure of the 28S human ribosomal RNA sequence at 65 °C using RNAfold program from the Vienna-RNA package;

[0042] Figs. 6A-6D are illustrations of the relative coverage depth for human host genes 12S, 16S, 18S and 28S rRNA in 45 UHTS experiments using random primers;

[0043] Figs. 7A-7D. are illustrations of the raw coverage depths for human host genes 12S, 16S, 18S and 28S rRNA in 45 UHTS experiments using random primers;

[0044] Fig. 8 is a schematic of the microbe RNA detection and amplification using the microbial enrichment primer procedure; and [0045] Fig. 9A and 9B are illustrations of the raw coverage depth of Lujo virus for its S and L segments, respectively, using the MEP primers and using random primers.

DETAILED DESCRIPTION OF THE INVENTION

[0046] The patent and scientific literature referred to herein establishes knowledge that is available to those of skill in the art. The issued U.S. patents, allowed applications, published foreign applications, and references, including GenBank database sequences, that are cited herein are hereby incorporated by reference to the same extent as if each was specifically and individually indicated to be incorporated by reference.

Definitions and Abbreviations

[0047] As used herein, the recitation of a numerical range for a variable is intended to convey that the invention may be practiced with the variable equal to any of the values within that range. Thus, for a variable which is inherently discrete, the variable can be equal to any integer value within the numerical range, including the end-points of the range.

Similarly, for a variable which is inherently continuous, the variable can be equal to any real value within the numerical range, including the end-points of the range. As an example, and without limitation, a variable which is described as having values between 0 and 2 can take the values 0, 1 or 2 if the variable is inherently discrete, and can take the values 0.0, 0.1, 0.01, 0.001, or any other real values > 0 and≤ 2 if the variable is inherently continuous.

[0048] As used herein, unless specifically indicated otherwise, the word "or" is used in the inclusive sense of "and/or" and not the exclusive sense of "either/or."

[0049] The singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise.

[0050] The term "about" is used herein to mean approximately, in the region of, roughly, or around. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about" is used herein to modify a numerical value above and below the stated value by a variance of 20%.

[0051] The term "microbe" as used herein refers to bacteria, viruses, fungi, parasites, and other infectious agents that are capable of infecting a host. As used herein, the term "host" or "organism" refers to any selected source that is infected or could potentially be infected with a microbe. Non- limiting examples of organisms include vertebrates, invertebrates, mammals, humans, dogs, cats, cattle, pigs, sheep, rabbits, mice, rats, birds, reptiles, amphibians, fish, insects, plants, tissue cultures, and cell cultures. As used herein, the term "sample" refers to material obtained from an organism. Non-limiting examples of samples include tissue, body fluids, blood, saliva, sperm, cells.

[0052] The coverage depth of a sequence region is the number of sequence reads which contain this region (i.e., they "cover" it). It does not have units as it is a count of reads. It is measured using the 454 reference mapper application. To increase the sensitivity of detection of a microbe infection, it is desirable to increase coverage depth (number of reads) for microbial sequences and to decrease it for the common host sequences.

[0053] In certain aspects, the present disclosure is directed to nucleic acid sequences as described herein for amplification of microbial nucleic acids from samples. Amplification can be performed by any suitable method known in the art, for example but not limited to polymerase chain reaction ("PCR"), real-time polymerase chain reaction ("RT- PCR"), and transcription mediated amplification (TMA). Nucleic amplification methods are disclosed in detail by Sambrook et al. (1989) Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y ("Sambrook"), which is incorporated herein by reference.

[0054] UHTS refers to Unbiased High Throughput Sequencing.

[0055] As used herein, "MEP primers" or "Microbial Enrichment Primers" or "microbe enrichment primers" refers to a set of primers designed or obtained using the methods described herein, which take into account the highly expressed host genes and the secondary structure of the RNA transcripts to be amplified.

[0056] As used herein, the phrases "forward strand microbial enrichment primers" and "FS-MEP" refer to microbial enrichment primers or a set of microbial enrichment primers that used to generate a first cDNA strand from the total RNA. In some embodiments, FS-MEP are of the formula H-N-ST described above where H is a nucleic acid hexamer (i.e., six nucleotides) N is a random nucleotide, and ST is a Specific Tail Sequence. The forward strand microbial enrichment primers are designed not to amplify transcripts from the highly expressed genes of an organism and include primers that are complementary to organism's RNA predicted to form a secondary structure.

[0057] As used herein, the phrases "reverse strand microbial enrichment primers" and "RS-MEP" refer to microbial enrichment primers or a set of microbial enrichment primers used to generate a second cDNA strand that is complementary to the first cDNA strand generated using FS-MEP. In some embodiments, RS-MEP are of the formula H-N-ST described above where H is a nucleic acid hexamer (i.e., six nucleotides), N is a random nucleotide and ST is a Specific Tail Sequence. In some embodiments, the hexamers (H) of the RS-MEP are complementary to the hexamers (H) of the FS-MEP.

[0058] In one aspect, the invention relates to a composition comprising 20 or more nucleic acid sequences, wherein each of the 20 nucleic acid sequence comprises a different hexamer sequence selected from the group consisting of the hexamers sequences of any of SEQ ID NOs: 1-1662, SEQ ID NOs: 1663-2490, or SEQ ID NOs: 2491-3324, provided that at least one nucleic sequence does not comprise a hexamer sequence selected from the group consisting of the hexamer sequences of any of SEQ ID NOs: 3325-4822. In certain embodiments, the composition comprising 20 or more nucleic acid sequences comprises 200 or more nucleic acid sequences. In certain embodiments, the composition comprising 20 or more nucleic acid sequences comprises 800 or more nucleic acid sequences. In certain embodiments, the composition comprising 20 or more nucleic acid sequences comprises is a composition wherein each nucleic acid further comprises a tail sequence 5 ' to the hexamer sequence, and wherein the tail sequence is about 10 to about 22 nucleotides in length, and wherein tail sequence is separated from the hexamer sequence by 0 to 10 nucleotides, and wherein each nucleic acid comprises the same tail sequence. In certain embodiments, the composition comprising 20 or more nucleic acid sequences is a composition wherein each nucleic acid sequence has the same length or substantially the same length. In certain embodiments, the composition comprising 20 or more nucleic acid sequences is a

composition wherein each nucleic acid has the hexamer sequence in the same position in the nucleic acid. In certain embodiments, the composition comprising 20 or more nucleic acid sequences is a composition wherein each nucleic acid sequence is a primer. In certain embodiments, the composition comprising 20 or more nucleic acid sequences is a

composition wherein each nucleic sequence is DNA, RNA, PNA, LNA, GNA or TNA.

[0059] In one aspect, the invention relates to a method for designing a primer set for amplification of microbial nucleic acids in an organism comprising: (a) sequencing RNA molecules in the transcriptome of an organism to generate a plurality of RNA sequence reads, (b) identifying a set of high copy redundant sequence reads from the plurality of sequence reads of step (a), wherein each high copy redundant sequence read is a sequence read representing at least about 1% of the total number of sequence reads identified in the plurality of sequences reads of step (a), (c) identifying a set of highly expressed RNA molecules comprising a sequence having at least about 95% sequence identity to a high copy redundant sequence read, (d) providing a first primer library, wherein each primer comprises a different hexamer sequence; and (e) generating a second primer library by removing primers from the first primer library predicted to anneal to one or more the RNA molecules in the set of highly expressed RNA molecules identified in step (d), provided that primers predicted to anneal to a region of a RNA predicted to have a strong secondary structure capable of impeding binding of a hexamer to the RNA are not removed from the first primer library. In certain embodiments, any one of steps (b), (c) or (e) are performed by a computer.In certain embodiments, the set of highly expressed RNA molecules identified in step (c) comprises any one of 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase, or NADH

dehydrogenase. In certain embodiments, the set of highly expressed RNA molecules identified in step (c) comprises one or more oxidative phosphorylation genes. In certain embodiments, the sequencing of step (a) is unbiased high throughput sequencing. In certain embodiments, the second primer library comprises 20 or more primers. In certain

embodiments, the second primer library comprises at least 800 primers. In certain

embodiments, the second primer library comprises at least 1600 primers. In certain embodiments, the method further comprises a step of generating DNA primers having the sequences of the primers if the second primer library. In certain embodiments, the method further comprises steps of, (i) generating cDNA from a RNA test sample using the second primer library and, (ii) generating cDNA complementary to the cDNA generated in step (i). In certain embodiments, the organism is a eukaryote. In certain embodiments, the organism is a human.

Identification of Microbes in Tissue Samples

[0060] Microbes in tissue samples can be identified by detecting their genetic signatures in the genetic background of a host. Traditionally, tissue samples are processed to recover genetic information as ribonucleic acid (RNA). RNAs are subsequently reverse- transcribed into cDNA and amplified prior to being sequenced with the 454-Roche sequencing platform. Reverse transcription is conducted using random primers ensuring an unbiased process. This procedure ensures that all RNA molecules present in the sample are represented in the cDNA library. Conversely, it is expected that an RNA species highly present in a sample will generate a higher number of reads. Practically, the 454-Roche sequencing platform generates a high, but limited, number of sequences (typically a few 100,000s).

Interference of Host Sequences with Detection of Microbe Detection

[0061] Identification of nucleic acids of microbes in tissue specimens by UHTS is greatly impeded by the presence of a large quantity of host RNA, especially ribosomal RNA (rRNA) which accounts for about 90-95% RNA species in total RNA. Thus, 90 to 95% of the sequence reads will be associated to rRNA, the remaining 5-10% of the sequencing reads will identify other host genes and potentially genetic signature of microbes. Hence, the host genetic material constitutes the vast majority of the sequence reads thus reducing the chance to detect a microbe in tissue samples.

[0062] 18S and 28S rRNA, mitochondrial 12S and 16S rRNA and oxidative phosphorylation (OxPhos) genes are known to be highly expressed genes. The oxidative phosphorylation genes include, but are not limited to, ATP synthase, cytochrome, fumarate reductase, NADH dehydrogenase, and polyphosphate kinase genes.

[0063] Armour et al. recently developed a procedure that allows generation of rRNA-depleted cDNA libraries using a selective collection of hexamers (1). The 'not- so- random' (NSR) primer collection was selected from in silico analyses of ribosomal RNA sequences present in public databases. All possible hexamer sequences with perfect sequence matches to human mitochondrial rRNA(12S, 16S) and ribosomal (18S, 28S) rRNA sequences were removed from the set of the initial random hexamer primers (4096 primers) (1). The NSR primer collection comprises 749 hexamers providing unbiased cDNA libraries.

[0064] Despite the proffered efficiency of the method of Armour (1), additional highly expressed genes contribute to the large number of host sequence reads identified in UHTS experiments (in particular, mitochondrial OxPhos genes). However, removing additional primers from the NSR primer collection to deplete additional highly expressed host genes would decrease significantly the number of NSR primers and the library complexity, adversely affecting the unbiased processes and reducing the chance to identify an unknown microbe.

[0065] In contrast with the method of Armour et al., the method for designing primers described herein is based, in part, on analyses of host sequences detected in unbiased high throughput sequencing experiments rather than in silica analyses of sequences in public databases. [0066] The advantages of the methods described herein include: (1) a more uniform coverage depth for microbe sequences; (2) depletion of a larger number of host genes; and/or (3) provision of a universal primer kit for a set of closely related organisms.

[0067] An analysis of 45 UHTS experiments (i.e., using random primers) generated with the 454-Roche sequencing platform revealed a non-uniform coverage depth of host genes, such as ribosomal (18S rRNA and 28S rRNA) and mitochondrial (12S rRNA, 16S rRNA, ATP Synthase, NADH dehydrogenase) genes. Fig. 2 shows the analysis of a 454 high- throughput sequencing experiment with the random primer set. Coverage depth for all positions in the 28S ribosomal RNA sequence using the 454 reference mapper application was identified. Fig. 2 shows that there are many reads coming from specific regions, while some other regions do not contribute any reads. This pattern was repeatedly observed through many experiments.

Secondary RNA Structure Impact on Primer Selection

[0068] This invention is based, in part, on the surprising discovery of a strong correlation between the presence of secondary structures in the target RNAs and the low coverage depth. It is presumed that strong secondary structures impede binding of random hexamers to the RNA template and the synthesis of the complementary DNA (Fig. 1). Thus, it is postulated that only primers that hybridize to the mRNA of the target gene that does not form a RNA secondary structure are able to generate sequencing reads. These observations allow for minimization of the number of primers to be removed from the set of random primers. If each primer contains a random hexamer nucleotides sequence NNNNNN, the set of random primers would comprise 4⁶ primers (4096 primers).

[0069] The primary structure of an organism's RNA determines which hexamers can bind to it with maximal efficiency. This happens when there is an exact match between the hexamer sequence and the sequence of the host RNA to which it binds. In one

embodiment, this occurs when there is exact complementarity between the hexamer sequence and the sequence of the host RNA to which it binds. However, the secondary RNA structure analysis of an organism's RNA reveals that not all possible binding sites are of equal importance and that strong secondary structures impede binding of random hexamers to the RNA template. For example, in silico analyses of 28S rRNA secondary structure suggests that the absence of host 28S rRNA reads in specific regions is correlated with strong secondary structures in those regions. Based on these findings, only those primers that can anneal to the host regions for ribosomal RNA (12S, 16S, 18S, 28S) and mitochondrial RNA identified in the UHTS results were excluded from the initial primer library. A set of primers obtained using this method is referred to as set of MEP primers.

[0070] Many methods can be used to determine secondary structure of RNA. There are a number of algorithms that predict RNA secondary structures based on thermodynamic parameters and energy calculations. For example, RNA secondary structure can be predicted using RNAfold program from the Vienna-RNA package (Hofacker et al., "Fast Folding and Comparison of RNA Secondary Structures," Monatshefte fur Chemie 125, 167-188 (1994). Alternatively or in addition, RNA secondary structure prediction can also performed using either M-fold (Matthews et al. (1999), J. Mol. Biol. 288:911-940) or RNA Structure 2.52. M-fold can be accessed through the internet at

infold.bioinfo.rpi.edu/download/ (last visited 12/16/2010). Additional software for RNA secondary structure production includes programs such as RNAfield, RNAstructure and UNAFold.

[0071] In contrast to Armour's work, the MEP primer design is based on analyses of host sequences detected in UHTS experiments rather than in silico analyses of sequences in public databases. The primer removal algorithm in the MEP primer design not only takes into account the primer sequence, but also RNA secondary structures. This approach allows for the depletion of a larger set of host genes without impacting on the cDNA library complexity.

Microbial Enrichment Primers (MEP)

[0072] In some embodiments, each MEP primer has the following structure:

Hexamer + N + Specific Tail

where Hexamer represents a sequence of 6 nucleotides, N is a spacer or 0 to 10 nucleotides, and Specific Tail is a sequence of 10-22 nucleotides. In some embodiments, each primer in a primer set has the same Specific Tail, but a different Hexamer. In general, all of the primers in the set have the same length or substantially the same length.

[0073] In some embodiments, H is a nucleic acid hexamer (i.e., a hexanucleotide) having a hexanucleotide sequence selected from the sequences in Table 1.

TA B L E 1

ATACAT SEQ ID: 204 TGACAA SEQ ID: 758 1 ' s GGTACG SEQ ID: 1312

ATACCG SEQ ID: 205 111 TGACGT SEQ ID: 759 β 1111ΐ1ι GGTACT SEQ ID: 1313

ATACCT SEQ ID: 206 TGACTC SEQ ID: 760 GGTAGA SEQ ID: 1314

ATACGC SEQ ID: 207 turn TGACTG SEQ ID: 761 GGTAGG SEQ ID: 1315

ATACGG SEQ ID: 208 111 11 GAG AC SEQ ID: 762 1 GGTATC SEQ ID: 1316

ATACGT SEQ ID: 209 TGATAC SEQ ID: 763 GGTATG SEQ ID: 1317

ATAGCA SEQ ID: 210 TGCAAG SEQ ID: 764 GGTATT SEQ ID: 1318

ATAGTC SEQ ID: 21 1 Hi 11 TGCACA SEQ ID: 765 iiiii

11111 GGTCCA SEQ ID: 1319

ATATAC SEQ ID: 212 TGCAGG SEQ ID: 766 11 GGTCTA SEQ ID: 1320

ATATCC SEQ ID: 213 11 TGCAGT SEQ ID: 767 S8JJJJ

1 GGTGAT SEQ ID: 1321

ATATCG SEQ ID: 214 i l

ft TGCATA SEQ ID: 768 1 "111 GGTGCC SEQ ID: 1322

ATATTC SEQ ID: 215 111 TGCATC SEQ ID: 769 lift GGTTAC SEQ ID: 1323

ATCACC SEQ ID: 216 TGCCAA SEQ ID: 770 GGTTAT SEQ ID: 1324

ATCAGC SEQ ID: 217 TGCCAT SEQ ID: 771 GGTTGT SEQ ID: 1325

ATCATA SEQ ID: 218 S8JJJJ

111 TGCCGC SEQ ID: 772 1 GTAATA SEQ ID: 1326

ATCCGT SEQ ID: 219 ll s§lll

ft TGCCTA SEQ ID: 773 s

1111 GTAATG SEQ ID: 1327

A CGAC SEQ ID: 220 ill TGCGAA SEQ ID: 774 ^ tll G ACAG SEQ ID: 1328

ATCGCA SEQ ID: 221 TGCGAC SEQ ID: 775 i

11111 GTACAT SEQ ID: 1329

ATCTAC SEQ ID: 222 ft 11 TGCGCA SEQ ID: 776 1 GTACCA SEQ ID: 1330

ATCTCA SEQ ID: 223 TGCTGG SEQ ID: 777 GTACCT SEQ ID: 1331

ATCTGG SEQ ID: 224 TGGAAA SEQ ID: 778 GTACGC SEQ ID: 1332

ATCTTC SEQ ID: 225 in TGGAAG SEQ ID: 779 11111 GTACGT SEQ ID: 1333

ATCTTG SEQ ID: 226 TGGAAT SEQ ID: 780 11111 GTACTA SEQ ID: 1334

A G AC A SEQ ID: 227 ft 11 TGGACA SEQ ID: 781 1 G AG AC SEQ ID: 1335

ATGAGG SEQ ID: 228 i l

ft TGGACC SEQ ID: 782 1 "111 G TAG AT SEQ ID: 1336

ATGCAA SEQ ID: 229 111 TGGAGC SEQ ID: 783 lift GTAGGG SEQ ID: 1337

ATGCAT SEQ ID: 230 TGGCAG SEQ ID: 784 GTAGTG SEQ ID: 1338

ATGCCG SEQ ID: 231 TGGCAT SEQ ID: 785 GTATAT SEQ ID: 1339

ATGCGA SEQ ID: 232 ft TGGCGC SEQ ID: 786 S8JJJJ

1 GTATCA SEQ ID: 1340

ATGCTC SEQ ID: 233 ll

ft TGGCGT SEQ ID: 787 ss§lll

11111 GTATCG SEQ ID: 1341

ATGCTG SEQ ID: 234 ill TGGGAC SEQ ID: 788 ^ tll GTATCT SEQ ID: 1342

ATGGAC SEQ ID: 235 11 TGGGAG SEQ ID: 789 i i

11111 GTATGA SEQ ID: 1343

ATGGTG SEQ ID: 236 ft 11 TGGTAC SEQ ID: 790 1 GTATGC SEQ ID: 1344

ATGTAA SEQ ID: 237 i l

ft TGGTAT SEQ ID: 791 1 "111 GTATTA SEQ ID: 1345

ATGTAC SEQ ID: 238 ll

ft TGGTCT SEQ ID: 792 s 1i1l111l GTATTC SEQ ID: 1346

ATGTCA SEQ ID: 239 Hi 11 TGTAAC SEQ ID: 793 11111 GTATTT SEQ ID: 1347

ATGTCG SEQ ID: 240 TGTACT SEQ ID: 794 11111 GTCACG SEQ ID: 1348

ATGTGC SEQ ID: 241 ft 11 TGTAGT SEQ ID: 795 1 GTCACT SEQ ID: 1349

ATGTTG SEQ ID: 242 i l

ft TGTATC SEQ ID: 796 1 "111 GTCAGG SEQ ID: 1350

ATTACG SEQ ID: 243 ft TGTCAT SEQ ID: 797 GTCATG SEQ ID: 1351

ATTATC SEQ ID: 244 Hi 11 TGTCGA SEQ ID: 798 11111

11111 GTCCAC SEQ ID: 1352

ATTCAA SEQ ID: 245 TGTCGC SEQ ID: 799 1 GTCCCA SEQ ID: 1353

ATTCAC SEQ ID: 246 ft TGTCGG SEQ ID: 800 S8JJJJ

1 GTCCTC SEQ ID: 1354

ATTCGA SEQ ID: 247 ll

ft TGTCGT SEQ ID: 801 β 1111ΐ1ΐ GTCGAC SEQ ID: 1355

ATTCTC SEQ ID: 248 111 TGTCTT SEQ ID: 802 ^ tll GTCGAT SEQ ID: 1356

ATTGAT SEQ ID: 249 11 TGTGCA SEQ ID: 803 i i

11111 GTCGCA SEQ ID: 1357

ATTGCC SEQ ID: 250 111 111 TGTGCG SEQ ID: 804 11 GTCGTT SEQ ID: 1358

ATTGGA SEQ ID: 251 ft ½ TGTGGA SEQ ID: 805 S8JJJJ

1 GTCTAA SEQ ID: 1359

ATTTCC SEQ ID: 252 ll

ft TGTTCG SEQ ID: 806 β 1111ΐ1ΐ GTCTAC SEQ ID: 1360

ATTTCG SEQ ID: 253 ill 11 TGTTGC SEQ ID: 807 1111 GTCTAG SEQ ID: 1361

CTCTGC SEQ ID: 454 ATTGTC SEQ ID: 1008 1 TGGAGT SEQ ID: 1562

CTCTGT SEQ ID: 455 11 SEQ ID: 1009 e III§iI TGGCAG SEQ ID: 1563

C GAGA SEQ ID: 456 ATTTTA SEQ ID: 1010 TGGCTA SEQ ID: 1564

CTGAGT SEQ ID: 457 turn CAACAT SEQ ID: 101 1 TGGGAC SEQ ID: 1565

CTGCAA SEQ ID: 458 H 11 CAACGT SEQ ID: 1012 11 TGGTAC SEQ ID: 1566

CTGCAG SEQ ID: 459 CAACTG SEQ ID: 1013 TGGTCT SEQ ID: 1567

CTGCCA SEQ ID: 460 CAAGGC SEQ ID: 1014 TGTAAG SEQ ID: 1568

CTGGCC SEQ ID: 461 HI 11 CAATAC SEQ ID: 1015 1i11i1 TGTACC SEQ ID: 1569

CTGGGA SEQ ID: 462 CAATCG SEQ ID: 1016 1 TGTAGT SEQ ID: 1570

CTGTAA SEQ ID: 463 111 11 CAATTC SEQ ID: 1017 11 TGTATA SEQ ID: 1571

CTGTAC SEQ ID: 464 ft 11 C AC ATT SEQ ID: 1018 1 11 TGTATC SEQ ID: 1572

CTGTAG SEQ ID: 465 titi C AC CAT SEQ ID: 1019 lift TGTATT SEQ ID: 1573

CTGTCG SEQ ID: 466 CACCGA SEQ ID: 1020 TGTCAC SEQ ID: 1574

CTGTGA SEQ ID: 467 CACCGT SEQ ID: 1021 TGTCAT SEQ ID: 1575

CTTACA SEQ ID: 468 11 11 CACGAA SEQ ID: 1022 1 TGTCGC SEQ ID: 1576

CTTCGT SEQ ID: 469 ft 11 CACGAC SEQ ID: 1023 e II§IiI TGTCGT SEQ ID: 1577

CTTGTA SEQ ID: 470 ill CACGCT SEQ ID: 1024 ^ tli TGTCTA SEQ ID: 1578

GAAAAA SEQ ID: 471 11 CACGGC SEQ ID: 1025 TGTCTC SEQ ID: 1579

GAAACA SEQ ID: 472 ft 11 CACGTC SEQ ID: 1026 11 TGTCTT SEQ ID: 1580

GAAACG SEQ ID: 473 CACGTT SEQ ID: 1027 TGTGAC SEQ ID: 1581

GAAATG SEQ ID: 474 CACTCG SEQ ID: 1028 TGTGCA SEQ ID: 1582

GAACGA SEQ ID: 475 in 11 CACTGG SEQ ID: 1029 IiIiII TGTGCG SEQ ID: 1583

GAACGT SEQ ID: 476 C AG ACT SEQ ID: 1030 IIII TGTGGA SEQ ID: 1584

GAACTT SEQ ID: 477 ft 11 CAGAGA SEQ ID: 1031 11 ¾Is TGTGTC SEQ ID: 1585

GAAGCC SEQ ID: 478 ft 11 CAGAGT SEQ ID: 1032 1 11 TGTGTG SEQ ID: 1586

GAAGTC SEQ ID: 479 Hi CAGATG SEQ ID: 1033 lift TGTTAA SEQ ID: 1587

GAATAC SEQ ID: 480 CAGCAT SEQ ID: 1034 TGTTAC SEQ ID: 1588

GAATCA SEQ ID: 481 CAGCTG SEQ ID: 1035 TGTTAT SEQ ID: 1589

GAATTG SEQ ID: 482 ft 11 CAGGAA SEQ ID: 1036 1 TGTTCC SEQ ID: 1590

GACAAC SEQ ID: 483 ft 11 CAGGCT SEQ ID: 1037 IIII TGTTTC SEQ ID: 1591

GACAAG SEQ ID: 484 ill CAGGTA SEQ ID: 1038 ^ tli TGTTTG SEQ ID: 1592

GACAAT SEQ ID: 485 11 C AG TAG SEQ ID: 1039 TTAACG SEQ ID: 1593

GACACA SEQ ID: 486 ft 11 C AG TAT SEQ ID: 1040 11 TTAATG SEQ ID: 1594

GACAGA SEQ ID: 487 ft 11 CAGTCA SEQ ID: 1041 1 11 TTACAG SEQ ID: 1595

GACAGC SEQ ID: 488 ft 11 CAGTCT SEQ ID: 1042 s IiIlIlI TTACAT SEQ ID: 1596

GACATA SEQ ID: 489 Hi ½ CAGTGG SEQ ID: 1043 l IlIllIlIl TTACCG SEQ ID: 1597

GACCAC SEQ ID: 490 CAGTGT SEQ ID: 1044 IIII TTACCT SEQ ID: 1598

GACCAG SEQ ID: 491 ft 11 CATACG SEQ ID: 1045 11 ¾Is TTACGT SEQ ID: 1599

G AC CAT SEQ ID: 492 ft 11 CATAGA SEQ ID: 1046 1 11 TTACTC SEQ ID: 1600

GACCTT SEQ ID: 493 ft CATATG SEQ ID: 1047 TTACTG SEQ ID: 1601

GACGAA SEQ ID: 494 Hi ½ CATCCG SEQ ID: 1048 1 II11I1I1 TTAGCG SEQ ID: 1602

G AC GAT SEQ ID: 495 CATCGA SEQ ID: 1049 11 TTAGGC SEQ ID: 1603

GACGCG SEQ ID: 496 ft 11 CATCGG SEQ ID: 1050 1 TTAGGG SEQ ID: 1604

GACGGA SEQ ID: 497 ft 11 CATCGT SEQ ID: 1051 IIII TTATCG SEQ ID: 1605

GACGTA SEQ ID: 498 ill CATCTC SEQ ID: 1052 ^ tli TTATCT SEQ ID: 1606

GACGTG SEQ ID: 499 11 CATGCG SEQ ID: 1053 nIIil TTATGC SEQ ID: 1607

GACTCG SEQ ID: 500 111 111 CATGTA SEQ ID: 1054 ll TTATGT SEQ ID: 1608

GACTCT SEQ ID: 501 ft 11 CAT T AC SEQ ID: 1055 1 TTATTT SEQ ID: 1609

GACTGT SEQ ID: 502 ft 11 CAT TAG SEQ ID: 1056 s IiIlIlI TTCACG SEQ ID: 1610

GAGACA SEQ ID: 503 ill ½ CATTGA SEQ ID: 1057 l 1l1l1ll1l TTCACT SEQ ID: 161 1

GCCCAA SEQ ID: 554 IlCGGGAC SEQ ID: 1 108 T T T T T T SEQ ID: 1662

[0074] In some embodiments, H is a nucleic acid hexamer (i.e., a hexanucleotide) having a hexanucleotide sequence selected from the sequences in Table 2. The hexamers in Table 2 can be used for forward sense primers, for example in the FS-MEP primers.

TABLE 2

SEQ ID: 2304

SEQ ID: 2305

SEQ ID: 2306

SEQ ID: 2307

SEQ ID: 2308

SEQ ID: 2309

SEQ ID: 2310

SEQ ID: 231 1

SEQ ID: 2312

SEQ ID: 2313

SEQ ID: 2314

SEQ ID: 2315

SEQ ID: 2316

SEQ ID: 2317

SEQ ID: 2318

SEQ ID: 2319

SEQ ID: 2320

SEQ ID: 2321

SEQ ID: 2322

SEQ ID: 2323

SEQ ID: 2324

SEQ ID: 2325

SEQ ID: 2326

SEQ ID: 2327

SEQ ID: 2328

SEQ ID: 2329

SEQ ID: 2330

SEQ ID: 2331

SEQ ID: 2332

SEQ ID: 2333

SEQ ID: 2334

SEQ ID: 2335

SEQ ID: 2336

SEQ ID: 2337

SEQ ID: 2338

SEQ ID: 2339

SEQ ID: 2340

SEQ ID: 2341

SEQ ID: 2342

SEQ ID: 2343

SEQ ID: 2344

SEQ ID: 2345

SEQ ID: 2346

SEQ ID: 2347

SEQ ID: 2348

SEQ ID: 2349

SEQ ID: 2350

SEQ ID: 2351

SEQ ID: 2352

SEQ ID: 2353

SEQ ID: 2404

SEQ ID: 2405

SEQ ID: 2406

SEQ ID: 2407

SEQ ID: 2408

SEQ ID: 2409

SEQ ID: 2410

SEQ ID: 241 1

SEQ ID: 2412

SEQ ID: 2413

SEQ ID: 2414

SEQ ID: 2415

SEQ ID: 2416

SEQ ID: 2417

SEQ ID: 2418

SEQ ID: 2419

SEQ ID: 2420

SEQ ID: 2421

SEQ ID: 2422

SEQ ID: 2423

SEQ ID: 2424

SEQ ID: 2425

SEQ ID: 2426

SEQ ID: 2427

SEQ ID: 2428

SEQ ID: 2429

SEQ ID: 2430

SEQ ID: 2431

SEQ ID: 2432

SEQ ID: 2433

SEQ ID: 2434

SEQ ID: 2435

SEQ ID: 2436

SEQ ID: 2437

SEQ ID: 2438

SEQ ID: 2439

SEQ ID: 2440

SEQ ID: 2441

SEQ ID: 2442

SEQ ID: 2443

SEQ ID: 2444

SEQ ID: 2445

SEQ ID: 2446

SEQ ID: 2447

SEQ ID: 2448

SEQ ID: 2449

SEQ ID: 2450

SEQ ID: 2451

SEQ ID: 2452

SEQ ID: 2453

TGGTCT SEQ ID: 2454

TGTAAC SEQ ID: 2455

TGTACT SEQ ID: 2456

TGTAGT SEQ ID: 2457

TGTATC SEQ ID: 2458

TGTCAT SEQ ID: 2459

TGTCGA SEQ ID: 2460

TGTCGC SEQ ID: 2461

TGTCGG SEQ ID: 2462

TGTCGT SEQ ID: 2463

TGTCTT SEQ ID: 2464

TGTGCA SEQ ID: 2465

TGTGCG SEQ ID: 2466

TGTGGA SEQ ID: 2467

TGTTCG SEQ ID: 2468

TGTTGC SEQ ID: 2469

TTAAC SEQ ID: 2470

TTACAT SEQ ID: 2471

TTAGAA SEQ ID: 2472

T TAG AC SEQ ID: 2473

TTATTA SEQ ID: 2474

TTCCGG SEQ ID: 2475

TTCCTG SEQ ID: 2476

TTCGAG SEQ ID: 2477

TTCGCA SEQ ID: 2478

TTCGTG SEQ ID: 2479

TTGAAA SEQ ID: 2480

TTGACG SEQ ID: 2481

TTGCAG SEQ ID: 2482

TTGCCT SEQ ID: 2483

TTGCGA SEQ ID: 2484

TTGCTT SEQ ID: 2485

TTGGAA SEQ ID: 2486

TTGTCG SEQ ID: 2487

TTGTGC SEQ ID: 2488

TTTCCG SEQ ID: 2489

TTTGTC SEQ ID: 2490

[0075] In some embodiments, H is a nucleic acid hexamer (i.e., a hexanucleotide) having a hexanucleotide sequence selected from the sequences in Table 3. The hexamers in Table 3 can be used for reverse sense primers, for example in the RS-MEP primers.

TABLE 3

SEQ ID 2772 GTTATC SEQ ID: 3050

SEQ ID 2773 GTTCGG SEQ ID: 3051

SEQ ID 2774 GTTGCG SEQ ID: 3052

SEQ ID 2775 GTTGGC SEQ ID: 3053

SEQ ID 2776 GTTGGG SEQ ID: 3054

SEQ ID 2777 ¾GTTGTC SEQ ID: 3055

SEQ ID 2778 GTTGTG SEQ ID: 3056

SEQ ID 2779 GTTTAT SEQ ID: 3057

SEQ ID 2780 GTTTCA SEQ ID: 3058

SEQ ID 2781 GTTTCG SEQ ID: 3059

SEQ ID 2782 GTTTGC SEQ ID: 3060

SEQ ID 2783 GTTTTG SEQ ID: 3061

SEQ ID 2784 HGTTTTT SEQ ID: 3062

SEQ ID 2785 TAAAAT SEQ ID: 3063

SEQ ID 2786 TAACCG SEQ ID: 3064

SEQ ID 2787 TAACGT SEQ ID: 3065

SEQ ID 2788 TAACC SEQ ID: 3066

SEQ ID 2789 TAAGTT SEQ ID: 3067

SEQ ID 2790 TAATAA SEQ ID: 3068

SEQ ID 2791 TAATCT SEQ ID: 3069

SEQ ID 2792 TAATGC SEQ ID: 3070

SEQ ID 2793 TAATTG SEQ ID: 3071

SEQ ID 2794 TACAAG SEQ ID: 3072

SEQ ID 2795 ACACG SEQ ID: 3073

SEQ ID 2796 TACAGC SEQ ID: 3074

SEQ ID: 2797 TACAGG SEQ ID: 3075

SEQ ID: 2798 ACAG SEQ ID: 3076

SEQ ID: 2799 TACATA SEQ ID: 3077

SEQ ID: 2800 TACATC SEQ ID: 3078

SEQ ID: 2801 TACCAA SEQ ID: 3079

SEQ ID: 2802 TACCGA SEQ ID: 3080

SEQ ID: 2803 TACCTG SEQ ID: 3081

SEQ ID: 2804 TACGCT SEQ ID: 3082

SEQ ID: 2805 TACGGC SEQ ID: 3083

SEQ ID: 2806 TACGGG SEQ ID: 3084

SEQ ID: 2807 TACGGT SEQ ID: 3085

SEQ ID: 2808 TACGTA SEQ ID: 3086

SEQ ID: 2809 TACGTC SEQ ID: 3087

SEQ ID: 2810 TACGTT SEQ ID: 3088

SEQ ID: 281 1 TACTCG SEQ ID: 3089

SEQ ID: 2812 TACTGC SEQ ID: 3090

SEQ ID: 2813 TACTGT SEQ ID: 3091

SEQ ID: 2814 TACTTA SEQ ID: 3092

SEQ ID: 2815 AGACG SEQ ID: 3093

SEQ ID: 2816 AGA SEQ ID: 3094

SEQ ID: 2817 TAGCAC SEQ ID: 3095

SEQ ID: 2818 TAGCCG SEQ ID: 3096

SEQ ID: 2819 TAGCGC SEQ ID: 3097

SEQ ID: 2820 TAGCGT SEQ ID: 3098

SEQ ID: 2821 TAGGCA SEQ ID: 3099 TAGGTG SEQ ID: 3100

TAGTGC SEQ ID: 3101 TAGTGT SEQ ID: 3102 TATACG SEQ ID: 3103 TATATC SEQ ID: 3104 TATATG SEQ ID: 3105 TATCGA SEQ ID: 3106 TATCGC SEQ ID: 3107 TATCGG SEQ ID: 3108 TATCGT SEQ ID: 3109 TATCTT SEQ ID: 31 10 TATGAT SEQ ID: 31 1 1 TATGCA SEQ ID: 31 12 TATGCG SEQ ID: 31 13 TATGGA SEQ ID: 31 14 TATGGC SEQ ID: 31 15 TATGGG SEQ ID: 31 16 TATGTA SEQ ID: 31 17 TATGTC SEQ ID: 31 18 TATGTT SEQ ID: 31 19 TATTCG SEQ ID: 3120 TATTGG SEQ ID: 3121 TATTGT SEQ ID: 3122 TATTTG SEQ ID: 3123 TCACAG SEQ ID: 3124 TCACCG SEQ ID: 3125 TCACGC SEQ ID: 3126 TCACGG SEQ ID: 3127 TCACGT SEQ ID: 3128 TCACTT SEQ ID: 3129 TCAGAG SEQ ID: 3130 TCAGGC SEQ ID: 3131 TCAGGT SEQ ID: 3132 TCAGTG SEQ ID: 3133 TCATGA SEQ ID: 3134 TCATGC SEQ ID: 3135 TCATGG SEQ ID: 3136 TCATGT SEQ ID: 3137 TCCAAC SEQ ID: 3138 TCCACA SEQ ID: 3139 TCCACG SEQ ID: 3140 TCCAGA SEQ ID: 3141 TCCATT SEQ ID: 3142 TCCCAG SEQ ID: 3143 TCCCTT SEQ ID: 3144 TCCGAG SEQ ID: 3145 TCCGTC SEQ ID: 3146 TCCTGG SEQ ID: 3147 TCCTGT SEQ ID: 3148 TCCTTG SEQ ID: 3149

SEQ ID: 3150

SEQ ID: 3151

SEQ ID: 3152

SEQ ID: 3153

SEQ ID: 3154

SEQ ID: 3155

SEQ ID: 3156

SEQ ID: 3157

SEQ ID: 3158

SEQ ID: 3159

SEQ ID: 3160

SEQ ID: 3161

SEQ ID: 3162

SEQ ID: 3163

SEQ ID: 3164

SEQ ID: 3165

SEQ ID: 3166

SEQ ID: 3167

SEQ ID: 3168

SEQ ID: 3169

SEQ ID: 3170

SEQ ID: 3171

SEQ ID: 3172

SEQ ID: 3173

SEQ ID: 3174

SEQ ID: 3175

SEQ ID: 3176

SEQ ID: 3177

SEQ ID: 3178

SEQ ID: 3179

SEQ ID: 3180

SEQ ID: 3181

SEQ ID: 3182

SEQ ID: 3183

SEQ ID: 3184

SEQ ID: 3185

SEQ ID: 3186

SEQ ID: 3187

SEQ ID: 3188

SEQ ID: 3189

SEQ ID: 3190

SEQ ID: 3191

SEQ ID: 3192

SEQ ID: 3193

SEQ ID: 3194

SEQ ID: 3195

SEQ ID: 3196

SEQ ID: 3197

SEQ ID: 3198

SEQ ID: 3199

SEQ ID: 2644 GCGTAG SEQ ID: 2922 TGATTG SEQ ID: 3200

SEQ ID: 2645 GCGTAT SEQ ID: 2923 ill TGCAAC SEQ ID: 3201

SEQ ID: 2646 GCGTCT SEQ ID: 2924 fill TGCACA SEQ ID: 3202

SEQ ID: 2647 GC ACT SEQ ID: 2925 1111 TGCACC SEQ ID: 3203

SEQ ID: 2648 GCTAGC SEQ ID: 2926 ill TGCAGG SEQ ID: 3204

SEQ ID: 2649 Bill GCTAGT SEQ ID: 2927 TGCATC SEQ ID: 3205

SEQ ID: 2650 GCTATC SEQ ID: 2928 1 li1il1i TGCCCG SEQ ID: 3206

SEQ ID: 2651 GCTCCA SEQ ID: 2929 ll! TGCCGG SEQ ID: 3207

SEQ ID: 2652 GCTCGA SEQ ID: 2930 1111 TGCCGT SEQ ID: 3208

SEQ ID: 2653 GCTCGG SEQ ID: 2931 ill TGCGAC SEQ ID: 3209

SEQ ID: 2654 ^ GCTGAT TGCGAT

. SEQ ID: 2932 SEQ ID: 3210

SEQ ID: 2655 GCTGCC SEQ ID: 2933 ■ TGCGCA SEQ ID: 321 1

SEQ ID: 2656 GCTGCT SEQ ID: 2934 TGCGCG SEQ ID: 3212

SEQ ID: 2657 GCTGTA SEQ ID: 2935 111 TGCGCT SEQ ID: 3213

SEQ ID: 2658 iiiiii GCTGTC SEQ ID: 2936 111 TGCGTA SEQ ID: 3214

SEQ ID: 2659 i sillillilil; GCTGTG SEQ ID: 2937 ill

ill TGCTAC SEQ ID: 3215

SEQ ID: 2660 GCTGTT SEQ ID: 2938 1111 TGCTAG SEQ ID: 3216

SEQ ID: 2661 GC AT SEQ ID: 2939 ill TGCTAT SEQ ID: 3217

SEQ ID: 2662 GCTTCG SEQ ID: 2940 till TGCTCC SEQ ID: 3218

SEQ ID: 2663 GCTTCT SEQ ID: 2941 TGCTGA SEQ ID: 3219

SEQ ID: 2664 llii GGAAAT SEQ ID: 2942 1 il1l1 TGCTGG SEQ ID: 3220

SEQ ID: 2665 GGAAGC SEQ ID: 2943 TGCTGT SEQ ID: 3221

SEQ ID: 2666 illli GGACGT SEQ ID: 2944 111

ill TGCTTT SEQ ID: 3222

SEQ ID: 2667 iiiiii GGACTG SEQ ID: 2945 ill TGGACT SEQ ID: 3223

SEQ ID: 2668 iiiiii GGACTT SEQ ID: 2946 ill TGGAGT SEQ ID: 3224

SEQ ID: 2669 GGAGCT SEQ ID: 2947 TGGCAG SEQ ID: 3225

SEQ ID: 2670 ill GGAGGC SEQ ID: 2948 l TGGCTA SEQ ID: 3226

SEQ ID: 2671 GGATAT SEQ ID: 2949

SEQ ID: 2672 GGATGT 1l1ii TGGGAC SEQ ID: 3227

SEQ ID: 2950 1 TGGTAC SEQ ID: 3228

SEQ ID: 2673 GGCAAC SEQ ID: 2951 ill TGGTCT SEQ ID: 3229

SEQ ID: 2674 GGCAAT SEQ ID: 2952 ill TGTAAG SEQ ID: 3230

SEQ ID: 2675 1

Itltllti GGCAC SEQ ID: 2953 llii TGTACC SEQ ID: 3231

SEQ ID: 2676 illlli GGCAGA SEQ ID: 2954 1111 TGTAGT SEQ ID: 3232

SEQ ID: 2677 illlli GGCATC SEQ ID: 2955 TGTATA SEQ ID: 3233

SEQ ID: 2678 GGCCAG SEQ ID: 2956 ill

ill TGTATC SEQ ID: 3234

SEQ ID: 2679 GGCCTG SEQ ID: 2957 TGTATT SEQ ID: 3235

SEQ ID: 2680 lip ! i GGCCTT SEQ ID: 2958 ill TGTCAC SEQ ID: 3236

SEQ ID: 2681 GGC AG SEQ ID: 2959 till TGTCAT SEQ ID: 3237

SEQ ID: 2682 1 GGCTCC SEQ ID: 2960 ill TGTCGC SEQ ID: 3238

SEQ ID: 2683 i GGCTGT SEQ ID: 2961 TGTCGT SEQ ID: 3239

SEQ ID: 2684 GGCTTC SEQ ID: 2962 ill TGTCTA SEQ ID: 3240

SEQ ID: 2685 m ¾m§§1 GGGACC SEQ ID: 2963 nn

1111 TGTCTC SEQ ID: 3241

SEQ ID: 2686 illlill GGGACT SEQ ID: 2964 TGTCTT SEQ ID: 3242

SEQ ID: 2687 GGGCTC SEQ ID: 2965 ill

111 TGTGAC SEQ ID: 3243

SEQ ID: 2688 GGGGGT SEQ ID: 2966 lili TGTGCA SEQ ID: 3244

SEQ ID: 2689 GGGGTA SEQ ID: 2967 ill TGTGCG SEQ ID: 3245

SEQ ID: 2690 GGGGTG SEQ ID: 2968 lllll TGTGGA SEQ ID: 3246

SEQ ID: 2691 GGGGTT SEQ ID: 2969 TGTGTC SEQ ID: 3247

SEQ ID: 2692 GGGTAC SEQ ID: 2970 111 TGTGTG SEQ ID: 3248

SEQ ID: 2693 GGGTAG

;;;;;;;;;;;;! SEQ ID: 2971 111

■ TGTTAA SEQ ID: 3249 SEQ ID: 2694 GGGTGC SEQ ID: 2972 TGTTAC SEQ ID: 3250

SEQ ID: 2695 GGTACC SEQ ID: 2973 ill TGTTAT SEQ ID: 3251

SEQ ID: 2696 GGTACG SEQ ID: 2974 fill TGTTCC SEQ ID: 3252

SEQ ID: 2697 GGTACT SEQ ID: 2975 TGTTTC SEQ ID: 3253

SEQ ID: 2698 GG AGA 1111

SEQ ID: 2976 ill TGTTTG SEQ ID: 3254

SEQ ID: 2699 Bill GGTAGG SEQ ID: 2977 TTAACG SEQ ID: 3255

SEQ ID: 2700 GGTATC SEQ ID: 2978 1 li1il1i TTAATG SEQ ID: 3256

SEQ ID: 2701 GGTATG SEQ ID: 2979 ll! T ACAG SEQ ID: 3257

SEQ ID: 2702 GGTATT SEQ ID: 2980 1111 T ACAT SEQ ID: 3258

SEQ ID: 2703 GGTCCA SEQ ID: 2981 ill TTACCG SEQ ID: 3259

SEQ ID: 2704 ^ GGTCTA TTACCT

. SEQ ID: 2982 SEQ ID: 3260

SEQ ID: 2705 GGTGAT SEQ ID: 2983 ■ TTACGT SEQ ID: 3261

SEQ ID: 2706 GGTGCC SEQ ID: 2984 TTACTC SEQ ID: 3262

SEQ ID: 2707 GGTTAC SEQ ID: 2985 111 TTACTG SEQ ID: 3263

SEQ ID: 2708 iiiiii GGTTAT SEQ ID: 2986 111 TTAGCG SEQ ID: 3264

SEQ ID: 2709 i sillillilil; GGTTGT SEQ ID: 2987 ill

ill TTAGGC SEQ ID: 3265

SEQ ID: 2710 GTAATA SEQ ID: 2988 1111 TTAGGG SEQ ID: 3266

SEQ ID: 271 1 GTAATG SEQ ID: 2989 ill TTATCG SEQ ID: 3267

SEQ ID: 2712 GTACAG SEQ ID: 2990 till TTATCT SEQ ID: 3268

SEQ ID: 2713 GTACAT SEQ ID: 2991 TTATGC SEQ ID: 3269

SEQ ID: 2714 llii GTACCA SEQ ID: 2992 1 il1l1 TTATGT SEQ ID: 3270

SEQ ID: 2715 GTACCT SEQ ID: 2993 TTATTT SEQ ID: 3271

SEQ ID: 2716 illli GTACGC SEQ ID: 2994 111

ill TTCACG SEQ ID: 3272

SEQ ID: 2717 iiiiii GTACGT SEQ ID: 2995 ill TTCACT SEQ ID: 3273

SEQ ID: 2718 iiiiii G AC A SEQ ID: 2996 ill TTCAGG SEQ ID: 3274

SEQ ID: 2719 GTAGAC SEQ ID: 2997 TTCATC SEQ ID: 3275

SEQ ID: 2720 ill GTAGAT SEQ ID: 2998 l TTCATG SEQ ID: 3276

SEQ ID: 2721 GTAGGG SEQ ID: 2999

SEQ ID: 2722 GTAGTG 1l1ii TTCCAA SEQ ID: 3277

SEQ ID: 3000 1 TTCCAC SEQ ID: 3278

SEQ ID: 2723 GTATAT SEQ ID: 3001 ill TTCCTG SEQ ID: 3279

SEQ ID: 2724 GTATCA SEQ ID: 3002 ill TTCGAC SEQ ID: 3280

SEQ ID: 2725 1

Itltllti GTATCG SEQ ID: 3003 llii TTCGAG SEQ ID: 3281

SEQ ID: 2726 illlli GTATCT SEQ ID: 3004 1111 TTCGCA SEQ ID: 3282

SEQ ID: 2727 illlli GTATGA SEQ ID: 3005 TTCGGC SEQ ID: 3283

SEQ ID: 2728 GTATGC SEQ ID: 3006 ill

ill TTCGGT SEQ ID: 3284

SEQ ID: 2729 GTATTA SEQ ID: 3007 TTCGTC SEQ ID: 3285

SEQ ID: 2730 lip ! i GTATTC SEQ ID: 3008 ill TTCTAA SEQ ID: 3286

SEQ ID: 2731 GTATTT SEQ ID: 3009 till TTCTGG SEQ ID: 3287

SEQ ID: 2732 1 GTCACG SEQ ID: 3010 ill TTGAAT SEQ ID: 3288

SEQ ID: 2733 i GTCACT SEQ ID: 301 1 GAGA SEQ ID: 3289

SEQ ID: 2734 GTCAGG SEQ ID: 3012 ill TTGAGT SEQ ID: 3290

SEQ ID: 2735 m ¾m§§1 GTCATG SEQ ID: 3013 nn

1111 TTGATG SEQ ID: 3291

SEQ ID: 2736 illlill GTCCAC SEQ ID: 3014 TTGCAC SEQ ID: 3292

SEQ ID: 2737 GTCCCA SEQ ID: 3015 ill

111 TTGCAG SEQ ID: 3293

SEQ ID: 2738 GTCCTC SEQ ID: 3016 lili TTGCAT SEQ ID: 3294

SEQ ID: 2739 GTCGAC SEQ ID: 3017 ill TTGCGA SEQ ID: 3295

SEQ ID: 2740 GTCGAT SEQ ID: 3018 lllll TTGCGG SEQ ID: 3296

SEQ ID: 2741 GTCGCA SEQ ID: 3019 TTGCTA SEQ ID: 3297

SEQ ID: 2742 GTCGTT SEQ ID: 3020 111 TTGGAG SEQ ID: 3298

SEQ ID: 2743 GTCTAA

;;;;;;;;;;;;! SEQ ID: 3021 111

■ TTGGCA SEQ ID: 3299 SEQ ID: 2744 llll GTCTAC SEQ ID: 3022 TTGGCC SEQ ID: 3300

SEQ ID: 2745 GTCTAG SEQ ID: 3023 TTGGGC SEQ ID: 3301

SEQ ID: 2746 GTCTAT SEQ ID: 3024 TTGTAT SEQ ID: 3302

SEQ ID: 2747 GTCTCA SEQ ID: 3025 1111 TTGTCA SEQ ID: 3303

SEQ ID: 2748 i GTCTCT SEQ ID: 3026 till TTGTCC SEQ ID: 3304

SEQ ID: 2749 GTCTGA SEQ ID: 3027 TTGTCG SEQ ID: 3305

SEQ ID: 2750 Illli GTCTTA SEQ ID: 3028 111 TTGTGC SEQ ID: 3306

SEQ ID: 2751 GTGAAT SEQ ID: 3029 TTGTGT SEQ ID: 3307

SEQ ID: 2752 GTGACA SEQ ID: 3030 1111 TTGTTA SEQ ID: 3308

SEQ ID: 2753 iiiiiii GTGATA SEQ ID: 3031 ill TTGTTT SEQ ID: 3309

SEQ ID: 2754 GTGCCC SEQ ID: 3032 TTTAGG SEQ ID: 3310

SEQ ID: 2755 GTGCCG SEQ ID: 3033 TTTAGT SEQ ID: 331 1

SEQ ID: 2756 _ GTGCGA SEQ ID: 3034 TTTATG SEQ ID: 3312

SEQ ID: 2757 111 GTGCGC SEQ ID: 3035 111 TTTCAA SEQ ID: 3313

SEQ ID: 2758 iiiiiii GTGCGT SEQ ID: 3036 TTTCCA SEQ ID: 3314

SEQ ID: 2759 lllll¾ GTGCTA SEQ ID: 3037 111 TTTCCG SEQ ID: 3315

SEQ ID: 2760 ill GTGCTG SEQ ID: 3038 TTTCCT SEQ ID: 3316

SEQ ID: 2761 iiiiiii GTGGTC SEQ ID: 3039 1111 TTTGAG SEQ ID: 3317

SEQ ID: 2762 flllll GTGGTT SEQ ID: 3040 till TTTGCG SEQ ID: 3318

SEQ ID: 2763 GTGTCG SEQ ID: 3041 TTTGCT SEQ ID: 3319

SEQ ID: 2764 Illi GTGTCT SEQ ID: 3042 ill TTTGGC SEQ ID: 3320

SEQ ID: 2765 GTGTGG SEQ ID: 3043 TTTTCC SEQ ID: 3321

SEQ ID: 2766 GTTAAC SEQ ID: 3044 1111 TTTTGC SEQ ID: 3322

SEQ ID: 2767 flllll GT ACA SEQ ID: 3045 till TTTTTC SEQ ID: 3323

SEQ ID: 2768 G ACT SEQ ID: 3046 111 SEQ ID: 3324

[0076] In some embodiments of the primers of formula H-N-ST, H comprises more than six nucleotides. In some embodiments, H comprises fewer than six nucleotides. In some embodiments, N is 1, 2, or 3 random nucleotides. In some embodiments, ST is a specific tail sequence of 12 to 22 nucleotides. In some embodiments, ST is a specific tail sequence selected from the group consisting of 12 to 15, 13 to 16, 14 to 17, 15 to 18, 16 to 19, 17 to 20, 18 to 21, and 19 to 22 nucleotides. In some embodiments, ST is a specific tail sequence selected from the group consisting of 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22 nucleotides. In some embodiments, ST is a specific tail sequence of 17 nucleotides.

[0077] In some embodiments, the present disclosure relates to nucleic acid sequences having the formula X-H-N-ST-Y, where H is a nucleic acid hexamer; N is 1, 2, or 3 random nucleotides; X and Y are 0 to 3 random nucleotides; and ST is a specific tail sequence of 12 to 22 nucleotides. In some embodiments, H is more than six nucleotides. In other embodiments, H is fewer than six nucleotides. In some embodiments, N is 1, 2, or 3 random nucleotides. In some embodiments X is 0, 1, 2, or 3 random nucleotides. In other embodiments, Y is 0, 1, 2, or 3 random nucleotides. In some embodiments, X and Y are the same number of random nucleotides. In some embodiments, X and Y are both 0 random nucleotides.

[0078] In some embodiments, all primers in a set or in composition have substantially the same length. In some embodiments, all primers in a set or in a composition have the same length. In some embodiments, all primers in a set have the same specific tail.

[0079] In some embodiments, a primer set described herein can comprise anywhere between 20-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500, 1500-1600, 1600- 1700, 1700-1800, 1800-1900, or 1900-2000 primers, such that each primer contains a different hexamer sequence. Generally, about half of these primers will be used as Forward Primers (FP) about half as Reverse Primers (RP).

[0080] The number of primers in a MEP primer set will vary based on which genes are highly expressed in the organism and based on the desired sensitivity of the high- throughput sequencing experiment. In general, a larger primer library is expected to increase sensitivity of microbe detection.

[0081] In some embodiments, a set of forward strand primers (FS-MEP) is a set of 800-900 primers. In some embodiments, a set of reverse strand primers (FS-MEP) is a set of 800-900 primers.

[0082] In some embodiments, the Hexamer is a hexamer selected from Table 1. In some embodiments, a primer set includes at least one primer in which the hexamer sequence is not a sequence selected from Table 4.

TABLE 4

SEQ ID 3837 CGATAT SEQ ID: 4336

SEQ ID 3838 CGATGA SEQ ID: 4337

SEQ ID 3839 CGCAAC SEQ ID: 4338

SEQ ID 3840 CGCACA SEQ ID: 4339

SEQ ID 3841 CGCACT SEQ ID: 4340

SEQ ID 3842 CGCATC SEQ ID: 4341

SEQ ID 3843 CGCGTT SEQ ID: 4342

SEQ ID 3844 CGCTGT SEQ ID: 4343

SEQ ID: 3845 CGGATG SEQ ID: 4344

SEQ ID 3846 CGGATT SEQ ID: 4345

SEQ ID 3847 CGGCAT SEQ ID: 4346

SEQ ID 3848 CGGCCT SEQ ID: 4347

SEQ ID 3849 HCGGTAT SEQ ID: 4348

SEQ ID 3850 CGGTCT SEQ ID: 4349

SEQ ID 3851 CGGTTA SEQ ID: 4350

SEQ ID 3852 CGTAAT SEQ ID: 4351

SEQ ID 3853 CGTACT SEQ ID: 4352

SEQ ID 3854 CGTATC SEQ ID: 4353

SEQ ID 3855 CGTATG SEQ ID: 4354

SEQ ID 3856 H!CGTCAA SEQ ID: 4355

SEQ ID 3857 CGTCGA SEQ ID: 4356

SEQ ID 3858 CGTGAC SEQ ID: 4357

SEQ ID 3859 CGTGCT SEQ ID: 4358

SEQ ID 3860 CGTGGT SEQ ID: 4359

SEQ ID 3861 CGTGTA SEQ ID: 4360

SEQ ID: 3862 CGTTAC SEQ ID: 4361

SEQ ID: 3863 CGTTGT SEQ ID: 4362

SEQ ID: 3864 CGTTTC SEQ ID: 4363

SEQ ID: 3865 CTAAAG SEQ ID: 4364

SEQ ID: 3866 CTAACG SEQ ID: 4365

SEQ ID: 3867 C ACAG SEQ ID: 4366

SEQ ID: 3868 CTACGG SEQ ID: 4367

SEQ ID: 3869 C AG AC SEQ ID: 4368

SEQ ID: 3870 CTAGCG SEQ ID: 4369

SEQ ID: 3871 CTAGCT SEQ ID: 4370

SEQ ID: 3872 CTAGGC SEQ ID: 4371

SEQ ID: 3873 CTAGGT SEQ ID: 4372

SEQ ID: 3874 C ATAA SEQ ID: 4373

SEQ ID: 3875 CTATCG SEQ ID: 4374

SEQ ID: 3876 CTCACA SEQ ID: 4375

SEQ ID: 3877 CTCATG SEQ ID: 4376

SEQ ID: 3878 CTCCTG SEQ ID: 4377

SEQ ID: 3879 CTCCTT SEQ ID: 4378

SEQ ID: 3880 CTCGAA SEQ ID: 4379

SEQ ID: 3881 CTCGAG SEQ ID: 4380

SEQ ID: 3882 CTCGTT SEQ ID: 4381

SEQ ID: 3883 CTCTAC SEQ ID: 4382

SEQ ID: 3884 CTCTAT SEQ ID: 4383

SEQ ID: 3885 CTCTCA SEQ ID: 4384

SEQ ID: 3886 CTCTGC SEQ ID: 4385 SEQ ID: 3388 GTGAAT SEQ ID: 3887 CTCTGT SEQ ID: 4386

SEQ ID: 3389 ill GTGACA SEQ ID: 3888 1111 CTGAGC SEQ ID: 4387

SEQ ID: f

3390 GTGACT SEQ ID: 3889 CTGATA SEQ ID: 4388

SEQ ID: 3391 GTGAGA SEQ ID: 3890 CTGATT SEQ ID: 4389

SEQ ID: 3392 fill

Bill GTGAGC SEQ ID: 3891 ■ CTGCAA SEQ ID: 4390

SEQ ID: 3393 GTGCAA SEQ ID: 3892 CTGCCT SEQ ID: 4391

SEQ ID: 3394 GTGCAT SEQ ID: 3893 CTGCGC SEQ ID: 4392

SEQ ID: 3395 GTGCTA SEQ ID: 3894 CTGCTA SEQ ID: 4393

SEQ ID: 3396 GTGGAT SEQ ID: ill

3895 1111 CTGCTG SEQ ID: 4394

SEQ ID: iiiiii

3397 GTGGCA SEQ ID: 3896 ill CTGGTA SEQ ID: 4395

SEQ ID: 3398 GTGTAT SEQ ID: 3897 CTGGTC SEQ ID: 4396

SEQ ID: 3399 GTGTCT 1111

SEQ ID: 3898 111 CTGTAG SEQ ID: 4397

SEQ ID: 3400 GTTAAC SEQ ID: 3899 CTGTCG SEQ ID: 4398

SEQ ID: 3401 GTTAAG SEQ ID: 3900 i CTGTGC SEQ ID: 4399

SEQ ID: 3402 GTTGCA SEQ ID: 3901 CTGTGT SEQ ID: 4400

SEQ ID: 3403 GTTGCC SEQ ID: 3902 111

111 CTTAAC SEQ ID: 4401

SEQ ID: 3404 till GTTGCG SEQ ID: 3903 1111 CTTACA SEQ ID: 4402

SEQ ID: 3405 i illilllilll® GTTGCT SEQ ID: 3904 CTTACG SEQ ID: 4403

SEQ ID: 3406 GTTGGA 111

SEQ ID: 3905 CTTAGG SEQ ID: 4404

SEQ ID: 3407 GTTGGC SEQ ID: 3906 CTTATA SEQ ID: 4405

SEQ ID: 3408 GTTGTA SEQ ID: 3907 ill CTTATC SEQ ID: 4406

SEQ ID: 3409 GTTGTG SEQ ID: 3908 1 CTTATT SEQ ID: 4407

SEQ ID: 3410 i ^'m

¾lmllilil¾ GTTTAA SEQ ID: 11

3909 CTTCCA SEQ ID: 4408

SEQ ID: 341 1 ill! TAAAAA SEQ ID: 111

3910 ill CTTCTA SEQ ID: 4409

SEQ ID: 3412 TAAAAT SEQ ID: 391 1 CTTCTC SEQ ID: 4410

SEQ ID: 3413 till TAAAGA SEQ ID: 3912 1111 CTTGAG SEQ ID: 441 1

SEQ ID: 3414 TAAATA SEQ ID: 3913 |§|§ CTTGCA SEQ ID: 4412

SEQ ID: 3415 TAACAA SEQ ID: 3914 CTTTAC SEQ ID: 4413

SEQ ID: 3416 TAACCG SEQ ID: 3915 CTTTAT SEQ ID: 4414

SEQ ID: 3417 TAACGA SEQ ID: 3916 11111 CTTTCA SEQ ID: 4415

SEQ ID: 3418 111 TAAC C SEQ ID: 3917 GAAATC SEQ ID: 4416

SEQ ID: 3419 i lllillillil® TAAGAC SEQ ID: 3918 111 GAATAT SEQ ID: 4417

SEQ ID: 3420 TAAGGC SEQ ID: 3919 ill GAATCG SEQ ID: 4418

SEQ ID: 3421 TAAG A SEQ ID: 3920 GACACC SEQ ID: 4419

SEQ ID: 3422 Ill TAAGTG SEQ ID: 3921 111 GACATA SEQ ID: 4420

SEQ ID: 3423 TAATGG SEQ ID: 3922 §1 GACC A SEQ ID: 4421

SEQ ID: 3424 flflflfl TAATGT SEQ ID: 3923 GACGCC SEQ ID: 4422

SEQ ID: 3425 TACAAT SEQ ID: 3924 GACG A SEQ ID: 4423

SEQ ID: 3426 ACACG SEQ ID: 3925

SEQ ID: 111 G AC AG SEQ ID: 4424

3427 1111 TACAGC SEQ ID: 3926 11111 GACTCC SEQ ID: 4425

SEQ ID: 3428 ACAG SEQ ID: 3927 GACTCG SEQ ID: 4426

SEQ ID: III

3429 illll ACA C SEQ ID: 3928 fill

llfi GACTGC SEQ ID: 4427

SEQ ID: 3430 ACA G SEQ ID: 3929 1 GACTTG SEQ ID: 4428

SEQ ID: 3431 m 11m11 ACCAG SEQ ID: li11

3930 GACTTT SEQ ID: 4429

SEQ ID: 3432 till TACCCC SEQ ID: 3931 llll GAGAAT SEQ ID: 4430

SEQ ID: 3433 TACCCT SEQ ID: 3932 liiii?

Illlll® GAGACG SEQ ID: 4431

SEQ ID: 3434 lilt TACCGA SEQ ID: 3933 1111 GAGATA SEQ ID: 4432

SEQ ID: 3435 TACCTG SEQ ID: 3934 III GAGATC SEQ ID: 4433

SEQ ID: 3436 ill

1 AC GAT SEQ ID: 3935 111 GAGCAT SEQ ID: 4434

SEQ ID: 3437 TACGCA SEQ ID: 3936 111 GAGGCT SEQ ID: 4435 SEQ ID: 3438 TACGTC SEQ ID: 4436

SEQ ID: 3439 fill TACGTT SEQ ID: 4437

SEQ ID: 3440 TACTCA SEQ ID: 4438

SEQ ID: 3441 fill TAGAAG SEQ ID: 4439

SEQ ID: 3442 Bill AGACC SEQ ID: 4440

SEQ ID: 3443 TAGAGA SEQ ID: 4441

SEQ ID: 3444 TAGCAA SEQ ID: 4442

SEQ ID: 3445 TAGCAC SEQ ID: 4443

SEQ ID: 3446 llli TAGCAG SEQ ID: 4444

SEQ ID: 3447 TAGCCA SEQ ID: 4445

SEQ ID: 3448 TAGGTC SEQ ID: 4446

SEQ ID: 3449 TAGGTG SEQ ID: 4447

SEQ ID: 3450 TAG T AC SEQ ID: 4448

SEQ ID: 3451 llli TAGTCG SEQ ID: 4449

SEQ ID: 3452 §§§§§§¾! TAGTGA SEQ ID: 4450

SEQ ID: 3453 TAGTGC SEQ ID: 4451

SEQ ID: 3454 till TATAAC SEQ ID: 4452

SEQ ID: 3455 illlll

§i§ii¾ TATAAG SEQ ID: 4453

SEQ ID: 3456 TATACA SEQ ID: 4454

SEQ ID: 3457 TATAGA SEQ ID: 4455

SEQ ID: 3458 Illll TAT C AG SEQ ID: 4456

SEQ ID: 3459 TATCTC SEQ ID: 4457

SEQ ID: 3460 11111111 TAT GAT SEQ ID: 4458

SEQ ID: 3461 llli TATGGC SEQ ID: 4459

SEQ ID: 3462 TATGTA SEQ ID: 4460

SEQ ID: 3463 till TATGTC SEQ ID: 4461

SEQ ID: 3464 Itltltl TATGTG SEQ ID: 4462

SEQ ID: 3465 TATTAA SEQ ID: 4463

SEQ ID: 3466 ■ iiiSSSSSi TAT T AC SEQ ID: 4464

SEQ ID: 3467 TATTCA SEQ ID: 4465

SEQ ID: 3468 till TCAATG SEQ ID: 4466

SEQ ID: 3469 illlll

lilisl TCAGAC SEQ ID: 4467

SEQ ID: 3470 TCAGCA SEQ ID: 4468

SEQ ID: 3471 Ill TCATAT SEQ ID: 4469

SEQ ID: 3472 11111 TCATCG SEQ ID: 4470

SEQ ID: 3473 TCATGA SEQ ID: 4471

SEQ ID: 3474 11111ft TCCACA SEQ ID: 4472

SEQ ID: 3475 illll TCCATC SEQ ID: 4473

SEQ ID: 3476 till TCCCAT SEQ ID: 4474

SEQ ID: 3477 till TCCGAT SEQ ID: 4475

SEQ ID: 3478 III TCGACA SEQ ID: 4476

SEQ ID: 3479 illll TCGACG SEQ ID: 4477

SEQ ID: 3480 TCGAGC SEQ ID: 4478

SEQ ID: 3481 TCGAGT SEQ ID: 4479

SEQ ID: 3482 lilt TCGATA SEQ ID: 4480

SEQ ID: 3483 illlll

iilisl TCGATG SEQ ID: 4481

SEQ ID: 3484 1 TCGCAA SEQ ID: 4482

SEQ ID: 3485 ill TCGCAC SEQ ID: 4483

SEQ ID: 3486 1 TCGGTG SEQ ID: 4484

SEQ ID: 3487 TCGTAT

SEQ ID: 4485

SEQ ID: 4586

SEQ ID: 4587

SEQ ID: 4588

SEQ ID: 4589

SEQ ID: 4590

SEQ ID: 4591

SEQ ID: 4592

SEQ ID: 4593

SEQ ID: 4594

SEQ ID: 4595

SEQ ID: 4596

SEQ ID: 4597

SEQ ID: 4598

SEQ ID: 4599

SEQ ID: 4600

SEQ ID: 4601

SEQ ID: 4602

SEQ ID: 4603

SEQ ID: 4604

SEQ ID: 4605

SEQ ID: 4606

SEQ ID: 4607

SEQ ID: 4608

SEQ ID: 4609

SEQ ID: 4610

SEQ ID: 461 1

SEQ ID: 4612

SEQ ID: 4613

SEQ ID: 4614

SEQ ID: 4615

SEQ ID: 4616

SEQ ID: 4617

SEQ ID: 4618

SEQ ID: 4619

SEQ ID: 4620

SEQ ID: 4621

SEQ ID: 4622

SEQ ID: 4623

SEQ ID: 4624

SEQ ID: 4625

SEQ ID: 4626

SEQ ID: 4627

SEQ ID: 4628

SEQ ID: 4629

SEQ ID: 4630

SEQ ID: 4631

SEQ ID: 4632

SEQ ID: 4633

SEQ ID: 4634

SEQ ID: 4635

SEQ ID: 4636

SEQ ID: 4637

SEQ ID: 4638

SEQ ID: 4639

SEQ ID: 4640

SEQ ID: 4641

SEQ ID: 4642

SEQ ID: 4643

SEQ ID: 4644

SEQ ID: 4645

SEQ ID: 4646

SEQ ID: 4647

SEQ ID: 4648

SEQ ID: 4649

SEQ ID: 4650

SEQ ID: 4651

SEQ ID: 4652

SEQ ID: 4653

SEQ ID: 4654

SEQ ID: 4655

SEQ ID: 4656

SEQ ID: 4657

SEQ ID: 4658

SEQ ID: 4659

SEQ ID: 4660

SEQ ID: 4661

SEQ ID: 4662

SEQ ID: 4663

SEQ ID: 4664

SEQ ID: 4665

SEQ ID: 4666

SEQ ID: 4667

SEQ ID: 4668

SEQ ID: 4669

SEQ ID: 4670

SEQ ID: 4671

SEQ ID: 4672

SEQ ID: 4673

SEQ ID: 4674

SEQ ID: 4675

SEQ ID: 4676

SEQ ID: 4677

SEQ ID: 4678

SEQ ID: 4679

SEQ ID: 4680

SEQ ID: 4681

SEQ ID: 4682

SEQ ID: 4683

SEQ ID: 4684

SEQ ID: 4685

SEQ ID: 4686

SEQ ID: 4687

SEQ ID: 4688

SEQ ID: 4689

SEQ ID: 4690

SEQ ID: 4691

SEQ ID: 4692

SEQ ID: 4693

SEQ ID: 4694

SEQ ID: 4695

SEQ ID: 4696

SEQ ID: 4697

SEQ ID: 4698

SEQ ID: 4699

SEQ ID: 4700

SEQ ID: 4701

SEQ ID: 4702

SEQ ID: 4703

SEQ ID: 4704

SEQ ID: 4705

SEQ ID: 4706

SEQ ID: 4707

SEQ ID: 4708

SEQ ID: 4709

SEQ ID: 4710

SEQ ID: 471 1

SEQ ID: 4712

SEQ ID: 4713

SEQ ID: 4714

SEQ ID: 4715

SEQ ID: 4716

SEQ ID: 4717

SEQ ID: 4718

SEQ ID: 4719

SEQ ID: 4720

SEQ ID: 4721

SEQ ID: 4722

SEQ ID: 4723

SEQ ID: 4724

SEQ ID: 4725

SEQ ID: 4726

SEQ ID: 4727

SEQ ID: 4728

SEQ ID: 4729

SEQ ID: 4730

SEQ ID: 4731

SEQ ID: 4732

SEQ ID: 4733

SEQ ID: 4734

SEQ ID: 4735

SEQ ID: 3788 llll CAGTCT SEQ ID: 4287 TTCGGC SEQ ID: 4786

SEQ ID: 3789 CAGTGG SEQ ID: 4288 TTCTAA SEQ ID: 4787

SEQ ID: 3790 CAGTGT SEQ ID: 4289 1111 TTCTTC SEQ ID: 4788

SEQ ID: 3791 CAGTTC SEQ ID: 4290 TTGAAT SEQ ID: 4789

SEQ ID: 3792 i CATACA SEQ ID: 4291 till TTGAGA SEQ ID: 4790

SEQ ID: 3793 CA ACG SEQ ID: 4292 TTGAGG SEQ ID: 4791

SEQ ID: 3794 CA AC SEQ ID: 4293 111 TTGAGT SEQ ID: 4792

SEQ ID: 3795 Illli CATAGA SEQ ID: 4294 1111 TTGATG SEQ ID: 4793

SEQ ID: 3796 CATAGG SEQ ID: 4295 TTGCAC SEQ ID: 4794

SEQ ID: 3797 iiiiiii CATCAT SEQ ID: 4296 ill TTGCAG SEQ ID: 4795

SEQ ID: 3798 CATCCG SEQ ID: 4297 TTGCAT SEQ ID: 4796

SEQ ID: 3799 CATCCT SEQ ID: 4298 TTGCCG SEQ ID: 4797

SEQ ID: 3800 _ CATCGA SEQ ID: 4299 TTGCGA SEQ ID: 4798

SEQ ID: 3801 111 CATCGG SEQ ID: 4300 111 TTGCGG SEQ ID: 4799

SEQ ID: 3802 iiiiiii CATCGT SEQ ID: 4301 111 TTGCTA SEQ ID: 4800

SEQ ID: 3803 lllll¾ CATGCG SEQ ID: 4302 TTGGCA SEQ ID: 4801

SEQ ID: 3804 ill CATGTA SEQ ID: 4303 TTGGGC SEQ ID: 4802

SEQ ID: 3805 iiiiiii CAT T AC SEQ ID: 4304 1111 TTGTAT SEQ ID: 4803

SEQ ID: 3806 flllll CAT TAG SEQ ID: 4305 till TTGTCA SEQ ID: 4804

SEQ ID: 3807 CATTCA SEQ ID: 4306 TTGTCG SEQ ID: 4805

SEQ ID: 3808 Illi CATTGA SEQ ID: 4307 ill TTGTGC SEQ ID: 4806

SEQ ID: 3809 CATTGC SEQ ID: 4308 TTGTGT SEQ ID: 4807

SEQ ID: 3810 CCACAA 1111

SEQ ID: 4309 TTGTTA SEQ ID: 4808

SEQ ID: 381 1 flllll CCAGAT SEQ ID: 4310 till TTGTTT SEQ ID: 4809

SEQ ID: 3812 CCATCA SEQ ID: 431 1 TTTACA SEQ ID: 4810

SEQ ID: 3813 CCATCC SEQ ID: 4312 TTTAGG SEQ ID: 481 1

SEQ ID: 3814 _ CCATCG SEQ ID: 4313 TTTATG SEQ ID: 4812

SEQ ID: 3815 111 CCATTA SEQ ID: 4314 111 TTTCAA SEQ ID: 4813

SEQ ID: 3816 iiiiiii CCCATC SEQ ID: 4315 111 TTTCCT SEQ ID: 4814

SEQ ID: 3817 lllll¾ CCCCTG SEQ ID: 4316 TTTCGC SEQ ID: 4815

SEQ ID: 3818 ill CCCGCA SEQ ID: 4317 TTTGAG SEQ ID: 4816

SEQ ID: 3819 iiiiiii CCGACA SEQ ID: 4318 1111 TTTGCG SEQ ID: 4817

SEQ ID: 3820 flllll CCGCTT SEQ ID: 4319 till TTTGCT SEQ ID: 4818

SEQ ID: 3821 CCGGTT SEQ ID: 4320 TTTGGC SEQ ID: 4819

SEQ ID: 3822 CCGTAT SEQ ID: 4321 111 TTTTCC SEQ ID: 4820

SEQ ID: 3823 CCGTTT SEQ ID: 4322 1111 TTTTGC SEQ ID: 4821

ill TTTTTA SEQ ID: 4822

[0083] In some embodiments, a set of forward strand primers includes from 20- 100, 100-200, 200-400, 400-600, 600-800, or 800-10000 primers in which at least one hexamer sequence is not a sequence selected from the hexamer sequences in Table 4. In some embodiments, a set of reverse strand primers includes from 20-100, 100-200, 200-400, 400-600, 600-800, or 800-10000 primers in which at least one hexamer sequence is not a sequence selected from the hexamer sequences in Table 5. [0084] In some embodiments, a set of forward strand (FS-MEP) primers include a hexamer (H) sequence selected from the group consisting of hexamers in Table 2. In some embodiments, a set of reverse strand (RS-MEP) primers include primers a hexamer sequence selected from the group consisting of hexamers in Table 3.

[0085] In some embodiments, H is a hexamer sequence selected from Table 2. This embodiment can be useful in a set of forward strand (FS-MEP) primers.

TABLE 5

SEQ ID: 551 1

SEQ ID: 5512

SEQ ID: 5513

SEQ ID: 5514

SEQ ID: 5515

SEQ ID: 5516

SEQ ID: 5517

SEQ ID: 5518

SEQ ID: 5519

SEQ ID: 5520

SEQ ID: 5521

SEQ ID: 5522

SEQ ID: 5523

SEQ ID: 5524

SEQ ID: 5525

SEQ ID: 5526

SEQ ID: 5527

SEQ ID: 5528

SEQ ID: 5529

SEQ ID: 5530

SEQ ID: 5531

SEQ ID: 5532

SEQ ID: 5533

SEQ ID: 5534

SEQ ID: 5535

SEQ ID: 5536

SEQ ID: 5537

SEQ ID: 5538

SEQ ID: 5539

SEQ ID: 5540

SEQ ID: 5541

SEQ ID: 5542

SEQ ID: 5543

SEQ ID: 5544

SEQ ID: 5545

SEQ ID: 5546

SEQ ID: 5547

SEQ ID: 5548

SEQ ID: 5549

SEQ ID: 5550

SEQ ID: 5551

SEQ ID: 5552

SEQ ID: 5553

SEQ ID: 5554

SEQ ID: 5555

SEQ ID: 5556

SEQ ID: 5557

SEQ ID: 5558

SEQ ID: 5559

SEQ ID: 5560

CACAAC SEQ ID: 5061 ft 11 GCCTAG SEQ ID: 531 1 11 TTGCGA SEQ ID: 5561

CACACA SEQ ID: 5062 ill ft GCCTGA SEQ ID: 5312 TTGCGT SEQ ID: 5562

CACAGC SEQ ID: 5063 GCCTTG SEQ ID: 5313 TTGCTT SEQ ID: 5563

CACAGG SEQ ID: 5064 GCGAAA SEQ ID: 5314 TTGGAA SEQ ID: 5564

C AC A SEQ ID: 5065 ft 11 GCGACA SEQ ID: 5315 ill TTGTAA SEQ ID: 5565

CACCGA SEQ ID: 5066 GCGATA SEQ ID: 5316 TTGTAC SEQ ID: 5566

CACGAT SEQ ID: 5067 GCGATT SEQ ID: 5317 11 11 TTGTAT SEQ ID: 5567

CACTGA SEQ ID: 5068 ft GCGCAG SEQ ID: 5318 TTGTGC SEQ ID: 5568

CAGAAT SEQ ID: 5069 GCGCAT SEQ ID: 5319 liil TTGTGG SEQ ID: 5569

CAGAGA SEQ ID: 5070 ft 11 GCGCTA SEQ ID: 5320 111 TTTATA SEQ ID: 5570

C AG ATT SEQ ID: 5071 ft 11 GCGTAT SEQ ID: 5321 ft "111 TTTTAT SEQ ID: 5571

CAGCAC SEQ ID: 5072 111 n GCGTCT SEQ ID: 5322

[0086] In some embodiments, H is a hexamer selected from Table 3. This embodiment can be useful in a set of reverse strand (RS-MEP) primers.

TABLE 6

SEQ ID 5852 TATAAA SEQ ID 6101

SEQ ID 5853 TATAAT SEQ ID 6102

SEQ ID 5854 1111 TATACA SEQ ID 6103

SEQ ID 5855 TATACG SEQ ID 6104

SEQ ID 5856 till TATATC SEQ ID 6105

SEQ ID 5857 TATATG SEQ ID 6106

SEQ ID 5858 111 TATCCT SEQ ID 6107

SEQ ID 5859 1111 TATCGA SEQ ID 6108

SEQ ID 5860 TATCGC SEQ ID 6109

SEQ ID 5861 ill TATCGG SEQ ID 61 10

SEQ ID 5862 TATCGT SEQ ID 61 1 1

SEQ ID 5863 TATCTC SEQ ID 61 12

SEQ ID 5864 TATCTT SEQ ID 61 13

SEQ ID 5865 111 TA GAG SEQ ID 61 14

SEQ ID 5866 111 TATGAT SEQ ID 61 15

SEQ ID 5867 TATGCA SEQ ID 61 16

SEQ ID 5868 TATGCG SEQ ID 61 17

SEQ ID 5869 1111 TATGGC SEQ ID 61 18

SEQ ID 5870 till TATGGG SEQ ID 61 19

SEQ ID 5871 TATGTC SEQ ID 6120

SEQ ID 5872 ill TATGTT SEQ ID 6121

SEQ ID 5873 1111 TATTCG SEQ ID 6122

SEQ ID 5874 TATTGG SEQ ID 6123

SEQ ID 5875 till TATTGT SEQ ID 6124

SEQ ID 5876 TATTTA SEQ ID 6125

SEQ ID 5877 TATTTC SEQ ID 6126

SEQ ID 5878 TATTTG SEQ ID 6127

SEQ ID 5879 111 TCAATC SEQ ID 6128

SEQ ID 5880 111 TCACAG SEQ ID 6129

SEQ ID 5881 TCACAT SEQ ID 6130

SEQ ID 5882 TCACCG SEQ ID 6131

SEQ ID 5883 1111 TCACGG SEQ ID 6132

SEQ ID 5884 till TCACGT SEQ ID 6133

SEQ ID 5885 TCACTA SEQ ID 6134

SEQ ID 5886 111 TCACTC SEQ ID 6135

SEQ ID 5887 1111 TCAGAG SEQ ID 6136

SEQ ID 5888 TCAGGC SEQ ID 6137

SEQ ID 5889 till TCAGGT SEQ ID 6138

SEQ ID 5890 TCAGTG SEQ ID 6139

SEQ ID 5891 1111 TCATCC SEQ ID 6140

SEQ ID 5892 1111 TCATCG SEQ ID 6141

SEQ ID 5893 TCATGA SEQ ID 6142

SEQ ID 5894 111 TCATGC SEQ ID 6143

SEQ ID 5895 TCATGG SEQ ID 6144

SEQ ID 5896 TCATGT SEQ ID 6145

SEQ ID 5897 1111 TCATTC SEQ ID 6146

SEQ ID 5898 TCATTT SEQ ID 6147

SEQ ID 5899 111 TCCAAC SEQ ID 6148

SEQ ID 5900 TCCACA SEQ ID 6149

SEQ ID 5901 ill TCCAGA SEQ ID

6150 SEQ ID 5902 TCCCAG SEQ ID 6151

SEQ ID 5903 TCCTGT SEQ ID 6152

SEQ ID 5904 1111 TCCTTG SEQ ID 6153

SEQ ID 5905 TCGAAT SEQ ID 6154

SEQ ID 5906 till TCGACC SEQ ID 6155

SEQ ID 5907 TCGACG SEQ ID 6156

SEQ ID 5908 111 TCGACT SEQ ID 6157

SEQ ID 5909 1111 TCGAGC SEQ ID 6158

SEQ ID 5910 TCGAGT SEQ ID 6159

SEQ ID 591 1 ill TCGATC SEQ ID 6160

SEQ ID 5912 TCGCAA SEQ ID 6161

SEQ ID 5913 TCGCAT SEQ ID 6162

SEQ ID 5914 TCGCGT SEQ ID 6163

SEQ ID 5915 111 TCGGAC SEQ ID 6164

SEQ ID 5916 111 TCGGTA SEQ ID 6165

SEQ ID 5917 TCGGTG SEQ ID 6166

SEQ ID 5918 TCGTCG SEQ ID 6167

SEQ ID 5919 1111 TCGTCT SEQ ID 6168

SEQ ID 5920 till TCGTGT SEQ ID 6169

SEQ ID 5921 TCGTTA SEQ ID 6170

SEQ ID 5922 ill TCGTTC SEQ ID 6171

SEQ ID 5923 1111 TCGTTG SEQ ID 6172

SEQ ID 5924 TCTACG SEQ ID 6173

SEQ ID 5925 till TCTAGG SEQ ID 6174

SEQ ID 5926 TCTATA SEQ ID 6175

SEQ ID 5927 TCTCAC SEQ ID 6176

SEQ ID 5928 TCTCAG SEQ ID 6177

SEQ ID 5929 111 TCTCAT SEQ ID 6178

SEQ ID 5930 111 TCTCGT SEQ ID 6179

SEQ ID 5931 TCTCTA SEQ ID 6180

SEQ ID 5932 TCTCTG SEQ ID 6181

SEQ ID 5933 1111 TCTGCG SEQ ID 6182

SEQ ID 5934 till TCTGCT SEQ ID 6183

SEQ ID 5935 TCTGTC SEQ ID 6184

SEQ ID 5936 111 TCTGTT SEQ ID 6185

SEQ ID 5937 1111 TCTTAT SEQ ID 6186

SEQ ID 5938 TCTTCG SEQ ID 6187

SEQ ID 5939 till TCTTCT SEQ ID 6188

SEQ ID 5940 TCTTGT SEQ ID 6189

SEQ ID 5941 1111 TCTTTA SEQ ID 6190

SEQ ID 5942 1111 TGAAGT SEQ ID 6191

SEQ ID 5943 TGAATA SEQ ID 6192

SEQ ID 5944 111 TGAATC SEQ ID 6193

SEQ ID 5945 TGACAT SEQ ID 6194

SEQ ID 5946 TGACCG SEQ ID 6195

SEQ ID 5947 1111 TGACTT SEQ ID 6196

SEQ ID 5948 T GAG AT SEQ ID 6197

SEQ ID 5949 111 TGAGCG SEQ ID 6198

SEQ ID 5950 TGAGGG SEQ ID 6199

SEQ ID 5951 ill TGAGTA SEQ ID

6200 SEQ ID 5952 TGATAA SEQ ID 6201

SEQ ID 5953 GA AC SEQ ID 6202

SEQ ID 5954 1111 TGATCA SEQ ID 6203

SEQ ID 5955 TGATTC SEQ ID 6204

SEQ ID 5956 till TGATTG SEQ ID 6205

SEQ ID 5957 TGCAAC SEQ ID 6206

SEQ ID 5958 111 TGCACA SEQ ID 6207

SEQ ID 5959 1111 TGCACC SEQ ID 6208

SEQ ID 5960 TGCAGG SEQ ID 6209

SEQ ID 5961 ill TGCATC SEQ ID 6210

SEQ ID 5962 TGCCAC SEQ ID 621 1

SEQ ID 5963 TGCCGG SEQ ID 6212

SEQ ID 5964 TGCCGT SEQ ID 6213

SEQ ID 5965 111 TGCGAC SEQ ID 6214

SEQ ID 5966 111 TGCGCA SEQ ID 6215

SEQ ID 5967 TGCGCT SEQ ID 6216

SEQ ID 5968 TGCGTA SEQ ID 6217

SEQ ID 5969 1111 TGCTAC SEQ ID 6218

SEQ ID 5970 till TGCTAG SEQ ID 6219

SEQ ID 5971 TGCTAT SEQ ID 6220

SEQ ID 5972 ill TGCTCC SEQ ID 6221

SEQ ID 5973 1111 TGCTGA SEQ ID 6222

SEQ ID 5974 TGCTGG SEQ ID 6223

SEQ ID 5975 till TGCTGT SEQ ID 6224

SEQ ID 5976 TGCTTT SEQ ID 6225

SEQ ID 5977 TGGACT SEQ ID 6226

SEQ ID 5978 TGGAGT SEQ ID 6227

SEQ ID 5979 111 TGGCAG SEQ ID 6228

SEQ ID 5980 111 TGGCTA SEQ ID 6229

SEQ ID 5981 TGGGAC SEQ ID 6230

SEQ ID 5982 TGGTAC SEQ ID 6231

SEQ ID 5983 1111 TGGTAT SEQ ID 6232

SEQ ID 5984 till TGGTCT SEQ ID 6233

SEQ ID 5985 111 TGTAAG SEQ ID 6234

SEQ ID 5986 TGTACC SEQ ID 6235

SEQ ID 5987 1111 TGTAGT SEQ ID 6236

SEQ ID 5988 TGTATA SEQ ID 6237

SEQ ID 5989 till TGTATC SEQ ID 6238

SEQ ID 5990 TGTATT SEQ ID 6239

SEQ ID 5991 1111 TGTCAC SEQ ID 6240

SEQ ID 5992 1111 TGTCAT SEQ ID 6241

SEQ ID 5993 TGTCGA SEQ ID 6242

SEQ ID 5994 111 TGTCGC SEQ ID 6243

SEQ ID 5995 TGTCGT SEQ ID 6244

SEQ ID 5996 TGTCTT SEQ ID 6245

SEQ ID 5997 1111 TGTGAC SEQ ID 6246

SEQ ID 5998 TGTGCA SEQ ID 6247

SEQ ID 5999 111 TGTGGA SEQ ID 6248

SEQ ID 6000 TGTGTC SEQ ID 6249

SEQ ID 6001 ill TGTGTG SEQ ID

6250 SEQ ID 6002 TGTTAA SEQ ID 6251

SEQ ID 6003 TGTTAT SEQ ID 6252

SEQ ID 6004 1111 TGTTCG SEQ ID 6253

SEQ ID 6005 TGTTTC SEQ ID 6254

SEQ ID 6006 till TGTTTG SEQ ID 6255

SEQ ID 6007 TTAAAC SEQ ID 6256

SEQ ID 6008 111 TTAA A SEQ ID 6257

SEQ ID 6009 1111 T ACAA SEQ ID 6258

SEQ ID 6010 T ACAT SEQ ID 6259

SEQ ID 601 1 ill TTACCG SEQ ID 6260

SEQ ID 6012 TTACCT SEQ ID 6261

SEQ ID 6013 TTACGG SEQ ID 6262

SEQ ID 6014 TTACGT SEQ ID 6263

SEQ ID 6015 111 TTACTC SEQ ID 6264

SEQ ID 6016 111 TTACTG SEQ ID 6265

SEQ ID 6017 TTAGCG SEQ ID 6266

SEQ ID 6018 TTAGGC SEQ ID 6267

SEQ ID 6019 1111 TTAGGG SEQ ID 6268

SEQ ID 6020 till TTATCG SEQ ID 6269

SEQ ID 6021 TTATCT SEQ ID 6270

SEQ ID 6022 ill TTATGC SEQ ID 6271

SEQ ID 6023 1111 TTATGT SEQ ID 6272

SEQ ID 6024 TTATTG SEQ ID 6273

SEQ ID 6025 till TTATTT SEQ ID 6274

SEQ ID 6026 TTCACG SEQ ID 6275

SEQ ID 6027 TTCAGG SEQ ID 6276

SEQ ID 6028 TTCATC SEQ ID 6277

SEQ ID 6029 111 TTCATG SEQ ID 6278

SEQ ID 6030 111 TTCCAA SEQ ID 6279

SEQ ID 6031 TTCCTG SEQ ID 6280

SEQ ID 6032 TTCGAC SEQ ID 6281

SEQ ID 6033 1111 TTCGCA SEQ ID 6282

SEQ ID 6034 till TTCGCT SEQ ID 6283

SEQ ID 6035 TTCGGC SEQ ID 6284

SEQ ID 6036 111 TTCTAA SEQ ID 6285

SEQ ID 6037 1111 TTCTTC SEQ ID 6286

SEQ ID 6038 TTGAAT SEQ ID 6287

SEQ ID 6039 till GAGA SEQ ID 6288

SEQ ID 6040 TTGAGG SEQ ID 6289

SEQ ID 6041 1111 TTGAGT SEQ ID 6290

SEQ ID 6042 1111 TTGATG SEQ ID 6291

SEQ ID 6043 TTGCAC SEQ ID 6292

SEQ ID 6044 111 TTGCAG SEQ ID 6293

SEQ ID 6045 TTGCAT SEQ ID 6294

SEQ ID 6046 TTGCCG SEQ ID 6295

SEQ ID 6047 1111 TTGCGA SEQ ID 6296

SEQ ID 6048 TTGCGG SEQ ID 6297

SEQ ID 6049 111 TTGCTA SEQ ID 6298

SEQ ID 6050 TTGGCA SEQ ID 6299

SEQ ID 6051 ill TTGGGC SEQ ID

6300 CA AG SEQ ID: 5803 1111111 GTGGTC SEQ ID 6052 TTGTAT SEQ ID 6301

CATTCA SEQ ID: 5804 illlll GTGGTT SEQ ID 6053 TTGTCA SEQ ID 6302

CATTGA SEQ ID: 5805 GTGTCT SEQ ID 6054 TTGTCG SEQ ID 6303

CATTGC SEQ ID: 5806 GTTAAC SEQ ID 1111

6055 TTGTGC SEQ ID 6304

CCACAA SEQ ID: 5807 ill 11 GTTACT SEQ ID 6056 till TTGTGT SEQ ID 6305

CCAGAT SEQ ID: 5808 GTTAGA SEQ ID 6057 TTGTTA SEQ ID 6306

CCATCA SEQ ID: 5809 GTTAGC SEQ ID 6058 111 TTGTTT SEQ ID 6307

CCATCC SEQ ID: 5810 ■ 11 GTTATA SEQ ID 6059 TTTACA SEQ ID 6308

CCATCG SEQ ID: 581 1 ill GTTATC SEQ ID 1111

6060 TTTAGG SEQ ID 6309

CCATTA SEQ ID: 5812 111111 GTTCGG SEQ ID 6061 ill TTTATG SEQ ID 6310

CCCATC SEQ ID: 5813 Ill 111 GTTGCG SEQ ID 6062 TTTCAA SEQ ID 631 1

CCCCTG SEQ ID: 5814 1 GTTGTG SEQ ID 6063 TTTCCT SEQ ID 6312

CCCGCA SEQ ID: 5815 1111 GTTTAT SEQ ID 6064 TTTCGC SEQ ID 6313

CCGACA SEQ ID: 5816 ■ GTTTCA SEQ ID 6065 111 TTTGAG SEQ ID 6314

CCGCTT SEQ ID: 5817 iiiiiii GTTTGC SEQ ID 6066 TTTGCG SEQ ID 6315

CCGGTT SEQ ID: 5818 Illlll GTTTTG SEQ ID 6067 111 TTTGCT SEQ ID 6316

CCGTAT SEQ ID: 5819 1 t TAAAAT SEQ ID 6068 TTTGGC SEQ ID 6317

CCGTTT SEQ ID: 5820 111 ½1 TAAACA SEQ ID 6069 1111 TTTTCC SEQ ID 6318

111 11 till TTTTGC SEQ ID 6319

§ 111 111 TTTTTA SEQ ID 6320

[0087] In some embodiments, a primer set includes at least one primer in which the hexamer sequence H is not a sequence selected from Table 4.

[0088] The primers can be labeled by any suitable molecule and/or label known in the art. Non-limiting examples of suitable labels include fluorescent tags suitable for use in Real Time PCR amplification, for example TaqMan™, SYBR™ Green, TAMRA™ and/or FAM probes, radiolabels, and so forth. In certain embodiments, the primer further comprises a detectable non-isotopic label selected from the group consisting of a fluorescent molecule, a chemiluminescent molecule, an enzyme, a cofactor, an enzyme substrate, and a hapten.

Generation of a Set of MEP Primers

[0089] The selection of hexamers for use in MEP primer sets, as well as selection of MEP primers, is not microbe specific. It can depend, however, on the host or the tissue of the host, as these factors will determine which of the host genes are highly expressed. In some embodiments, primers that amplify host ribosomal and mitochondrial sequences are removed from the initial 4096 (4⁶) random hexamer set. For example, sequence data generated over the course of 800 high-throughput sequencing runs on the 454 sequencing platform were analyzed. These analyses show which host regions were amplified by the entire set of random hexamers. Primers that anneal to the host ribosomal and mitochondrial sequences are then removed from the initial primer library to generate a second primer library. The second library comprises a set of hexamer-containing primers that enrich the reads in a high throughput sequences for the presence of bacterial, viral, fungal, or parasite nucleic acids in a given organism.

[0090] In some embodiments, the primer library is generated as follows: (a) sequence reads representing all rRNA (12S, 16S, 18S, 28S) and mitochondrial RNA (ATP synthase, NADH dehydrogenase) present in 454-unbiased high throughput sequencing (UHTS) experiments are selected; (b) all combinations of hexamers (e.g., 3,268 primers) that anneal to host sequences identified in step (a), but not those that anneal to regions of rRNA and mitochondrial RNA predicted to form secondary structure, are excluded; and (c) 828 hexamer primers that do not bind to host sequences identified in step (a) are synthesized.

[0091] In some embodiments, the performance of the MEP primers can be validated in real time PCR experiments that confirmed depletion of host sequences and in 454 pyrosequencing experiments. In still another embodiment, sensitivity for detection of viral sequences is increased >1000X.

Amplification of Microbial Nucleic Acids with MEP Primers

[0092] Microbial nucleic acids can be amplified as follows. Total RNA can be extracted from the sample using commercially available kits (e.g., Qiagen, Valencia, CA). Contaminating genomic DNA is removed, for example with DNAsel (Qiagen, Valencia, CA) or by any other procedure or reagent that removes DNA, but not RNA. The resultant RNA is reverse transcribed using the forward-strand microbial enrichment primer set (FS-MEP) to generate first-strand cDNA, as illustrated in Fig. 3A. Reverse transcriptase is inactivated or removed. Next, second-strand cDNA synthesis is carried out with the reverse-strand microbial enrichment primer set (RS-MEP) in the presence of a polymerase enzyme as illustrated in Fig. 3B. The resultant double-stranded cDNA is amplified, for example using Extend primers (Roche Diagnostics, Branchburg, NJ), as illustrated in Fig. 3C. Other suitable primers can also be used for amplification of the resultant double-stranded cDNA, as long as they can hybridize to the Specific Tail sequence or a portion thereof under PCR conditions.

Detection of Microbial Nucleic Acids With MEP Primers

[0093] The nucleic acid sequences of the present disclosure are used as primers to amplify microbial nucleic acid in a sample from a host, without significantly amplifying the host's RNA in the sample. If the nucleic acid sequences successfully amplify nucleic acid in the sample, then the sample contains microbial nucleic acid, indicating that the sample is infected with microbes. This method is referred to herein as the "MEP protocol" or the "microbial enrichment primer protocol."

[0094] An exemplary method includes: providing a sample from an organism containing R A, reverse transcribing the R A in the sample using FS-MEP primers to form a first cDNA strand from. The method further includes generating a second cDNA strand that is complementary to the first cDNA strand using RS-MEP with hexamer sequences that are complementary to the hexamer sequences of FS-MEP. The method further includes PCR amplifying double-stranded cDNA using a first amplification primer having the same sequence as the special tail (ST) of the FS-MEP and a second amplification primer having a sequence complementary to the specific tail (ST) of the FS-MEP, thereby generating a population of double-stranded cDNA products. The method further includes determining the presence or absence of the amplified cDNA products, wherein the presence of the amplified cDNA products indicates the presence of a microbial nucleic acid in the sample.

[0095] In some embodiments the PCR amplification is done using real-time PCR. In some embodiments the first and second amplification primers are labeled. The primers can be labeled by any suitable molecule and/or label known in the art. Non-limiting examples of suitable labels include a radiolabel, a detectable non-isotopic label, a fluorescent molecule, a chemiluminescent molecule, an enzyme, a cofactor, an enzyme substrate, and a hapten.

[0096] In some embodiments, the method is used to detect RNA from a microbe selected from the group consisting of a bacterium, a virus, a fungi, and a parasite. In some embodiments, the microbe is a virus, an arenavirus, or Lujo virus. In some embodiments, the sample is from a subject, a mammal, or a human. In other embodiments, the sample is a biological sample. In some embodiments the biological sample is from a tissue culture or a cell culture. In some embodiments the sample is tissue, bodily fluids, blood, sperm saliva, or cells. In some embodiments, the sample is from a host. Non-limiting examples of hosts include organisms, vertebrates, invertebrates, mammals, humans, dogs, cats, cattle, pigs, sheep, rabbits, mice, rats, birds, reptiles, amphibians, fish, insects, plants, tissue cultures, and cell cultures.

Method of Making Microbial Enrichment Primers

[0097] Once the MEP primers are designed they can be synthesized using standard methods, such as by solid-phase synthesis using the phosphoramidite method. Microbial enrichment primer kits

[0098] In some embodiments, the invention provides a kit comprising a set of MEP primers and instructions for use. In some embodiments, the set of MEP primers is a set of forward-strand MEP (FS-MEP) primers. In some embodiments, the set of MEP primers is a set of reverse-strand MEP (FS-MEP) primers. In some embodiments, the set of MEP primers is a set of forward-strand MEP (FS-MEP) and reverse-strand MEP (FS-MEP) primers.

EXAMPLES

[0099] This invention is further illustrated by the following example, which should not be construed as limiting. Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific substances and procedures described herein. Such equivalents are intended to be encompassed in the scope of the claims that follow the examples below.

Example 1

Unbiased High Throughput Sequencing (UHTS) Experiments

[00100] 45 UHTS experiments from human tissue samples (retina, pancreas, liver, heart, lung, brain, plasma, serum, throat swab, cerebrospinal fluid, brain, liver, heart) were analyzed. The libraries were generated using random octamer primers according to the protocol previously described (2-3). Briefly, total R A was extracted and digested with DNAsel to eliminate human chromosomal DNA. RNA preparations were amplified by means of reverse transcriptase PCR (PCR) with the use of random primers. Amplification products were pooled and sequenced with the use of the GSL FLX platform (454 Life Sciences, Branford, CT), but DNA fragmentation was omitted (4).

Microbe Enrichment Primer (MEP) Design

[00101] Selection of the microbial enrichment primers is based on the analysis of sequence data generated over the course of 45 UHTS sequencing runs on the 454-Roche sequencing platform.

[00102] Step 1. For each library, sequence reads identified for human, 18S

(NR_003286) and 28S (NR_003287) rRNA and mitochondrial 12S (NC_012920, nt 648- 1601), 16S (NC_012920, nt 1671-3229), ATP Synthase (NC_012920), NADH dehydrogenase (ND2, ND4, ND6) (NC_012920) are selected and mapped to the reference sequences.

[00103] Step 2. The read distribution for each host gene listed in Step 1 is determined by coverage depth. The coverage depth for a given nucleotide in a reference sequence is evaluated as the number of reads that align to the reference sequence and cover this given nucleotide (Figs. 4A-B). Fig. 4A illustrates the read mapping procedure. Reads identified by 454 UHTS (Read 1 through 5) are aligned to the reference sequence (Ref. seq). The coverage depth (Depth) for a given nucleotide in the reference sequence is evaluated as the number of reads that align to the reference sequence and cover this given nucleotide. In this example the coverage depth for a given nucleotide ranges from 0 to 5. Fig. 4B is an illustrative plot of the coverage depth along the reference sequence allows to visualize the number of reads in each region.

[00104] Fig. 5 shows predicted secondary structure of the 28S human ribosomal RNA sequence at 65 °C using RNAfold program from the Vienna-RNA package (Hofacker et al, "Fast Folding and Comparison of RNA Secondary Structures," Monatshefte fur Chemie 125, 167-188 (1994). Regions which are GC-rich have strong secondary structure stems and no reads where identified in 454- unbiased high-throughput sequencing experiments.

[00105] A plot of the coverage depth as a function of the nucleotide position provides a quantitative measure of the non-uniformity of the read distribution. Figs. 6A-6D illustrate for all 45 UHTS experiments the normalized coverage depth for human genes 12S, 16S, 18S and 28S rRNA, respectively, when random primers are used. Figs. 7A-7D illustrate the raw coverage depth (number of reads) for the same experiments as Figs. 6A-6D, respectively. Identical analyses were conducted for mitochondrial host genes.

[00106] Step 3. Regions giving a large amount of reads (arbitrary cutoff: >1% of relative coverage depth) were selected. Figs. 6A-6D and Table 8 show the regions selected for 12S, 16S, 18S and 28S. Table 7 is a summary table of regions giving a large number of reads (>1% of relative coverage depth) for the ribosomal genes. Figs. 6A-6D show the location of those regions. Rl to R6 indicate the different regions selected for each ribosomal gene.

TABLE 7 Accession Regions

G&m ttame number selected

1 S NC_0 ! 2920 Complete gene

16S INC j012920 R1 , 2, R3

18S NC_01.2:920 Rl _r R2

R1 , R2, , 4,

[00107] Step 4. All possible hexamer sequences with perfect sequence matches to the host regions selected in Step 3 were excluded. Focusing on these specific host regions allows to exclude only a minimal number of primers from the random hexamer library.

[00108] The resulting microbe enrichment primer set, is composed of 828 hexamers for the forward sense primers (FS-MEP) and 834 hexamers for the reverse sense primers (RS- MEP). Each primer consists of a hexamer followed by a random base (N) and a specific tail:

Hexamer + N + Specific Tail

[00109] The Specific Tail sequence (Extend primer) was

GTTTCCCAGTAGGTCTC. Sequences of suitable the Hexamers are provided in Tables 1, 2 and 3.

[00110] The forward stand (FS-MEP) primer set used in this experiment is provided in Table 8.

TABLE 8

G I N CCCAGTAGGTCTC N AACAAG SEQ ID NO: 6335

GTTTCCCAGTAGGTCTC N AACAGC SEQ ID NO: 6336

GTTTCCCAGTAGGTCTC N AACATA SEQ ID NO: 6337

GTTTCCCAGTAGGTCTC N AACCAC SEQ ID NO: 6338

GTTTCCCAGTAGGTCTC N AACCCC SEQ ID NO: 6339

GTTTCCCAGTAGGTCTC N AACCGG SEQ ID NO: 6340

GTTTCCCAGTAGGTCTC N AACCGT SEQ ID NO: 6341

GTTTCCCAGTAGGTCTC N AACGAC SEQ ID NO: 6342

GTTTCCCAGTAGGTCTC N AACGAG SEQ ID NO: 6343

GTTTCCCAGTAGGTCTC N AACGAT SEQ ID NO: 6344

GTTTCCCAGTAGGTCTC N AACGCG SEQ ID NO: 6345

GTTTCCCAGTAGGTCTC N AACGTA SEQ ID NO: 6346

GTTTCCCAGTAGGTCTC N AACGTG SEQ ID NO: 6347

GTTTCCCAGTAGGTCTC N AACGTT SEQ ID NO: 6348

GTTTCCCAGTAGGTCTC N AACTAT SEQ ID NO: 6349

GTTTCCCAGTAGGTCTC N AACTCG SEQ ID NO: 6350

GTTTCCCAGTAGGTCTC N AACTGA SEQ ID NO: 6351

GTTTCCCAGTAGGTCTC N AACTTA SEQ ID NO: 6352

GTTTCCCAGTAGGTCTC N AACTTG SEQ ID NO: 6353

GTTTCCCAGTAGGTCTC N AAGACA SEQ ID NO: 6354

GTTTCCCAGTAGGTCTC N AAGACG SEQ ID NO: 6355

GTTTCCCAGTAGGTCTC N AAGATA SEQ ID NO: 6356

GTTTCCCAGTAGGTCTC N AAGCAG SEQ ID NO: 6357

GTTTCCCAGTAGGTCTC N AAGCGC SEQ ID NO: 6358

GTTTCCCAGTAGGTCTC N AAGCGG SEQ ID NO: 6359

GTTTCCCAGTAGGTCTC N AAGGAA SEQ ID NO: 6360

GTTTCCCAGTAGGTCTC N AAGGCC SEQ ID NO: 6361

GTTTCCCAGTAGGTCTC N AAGGGA SEQ ID NO: 6362

GTTTCCCAGTAGGTCTC N AAGGGT SEQ ID NO: 6363

GTTTCCCAGTAGGTCTC N AAGTCA SEQ ID NO: 6364

GTTTCCCAGTAGGTCTC N AAGTCC SEQ ID NO: 6365

GTTTCCCAGTAGGTCTC N AAGTCT SEQ ID NO: 6366

GTTTCCCAGTAGGTCTC N AAGTGA SEQ ID NO: 6367

GTTTCCCAGTAGGTCTC N AAGTGT SEQ ID NO: 6368

GTTTCCCAGTAGGTCTC N AATAAG SEQ ID NO: 6369

GTTTCCCAGTAGGTCTC N AATACA SEQ ID NO: 6370

GTTTCCCAGTAGGTCTC N AATACC SEQ ID NO: 6371

GTTTCCCAGTAGGTCTC N AATATC SEQ ID NO: 6372

GTTTCCCAGTAGGTCTC N AATCAG SEQ ID NO: 6373

GTTTCCCAGTAGGTCTC N AATCCG SEQ ID NO: 6374

GTTTCCCAGTAGGTCTC N AATCTA SEQ ID NO: 6375

GTTTCCCAGTAGGTCTC N AATGGC SEQ ID NO: 6376

GTTTCCCAGTAGGTCTC N AATGTG SEQ ID NO: 6377 G I N CCCAGTAGGTCTC N AATTCG SEQ ID NO: 6378

GTTTCCCAGTAGGTCTC N ACAACC SEQ ID NO: 6379

GTTTCCCAGTAGGTCTC N ACAACG SEQ ID NO: 6380

GTTTCCCAGTAGGTCTC N ACAAGA SEQ ID NO: 6381

GTTTCCCAGTAGGTCTC N ACAAGT SEQ ID NO: 6382

GTTTCCCAGTAGGTCTC N ACAATA SEQ ID NO: 6383

GTTTCCCAGTAGGTCTC N ACAATT SEQ ID NO: 6384

GTTTCCCAGTAGGTCTC N ACACAA SEQ ID NO: 6385

GTTTCCCAGTAGGTCTC N ACACAG SEQ ID NO: 6386

GTTTCCCAGTAGGTCTC N ACACGA SEQ ID NO: 6387

GTTTCCCAGTAGGTCTC N ACACTA SEQ ID NO: 6388

GTTTCCCAGTAGGTCTC N ACACTG SEQ ID NO: 6389

GTTTCCCAGTAGGTCTC N ACAGAG SEQ ID NO: 6390

GTTTCCCAGTAGGTCTC N ACAGCA SEQ ID NO: 6391

GTTTCCCAGTAGGTCTC N ACAGCC SEQ ID NO: 6392

GTTTCCCAGTAGGTCTC N ACAGCG SEQ ID NO: 6393

GTTTCCCAGTAGGTCTC N ACAGCT SEQ ID NO: 6394

GTTTCCCAGTAGGTCTC N ACAGGA SEQ ID NO: 6395

GTTTCCCAGTAGGTCTC N ACAGTA SEQ ID NO: 6396

GTTTCCCAGTAGGTCTC N ACATAA SEQ ID NO: 6397

GTTTCCCAGTAGGTCTC N ACATAT SEQ ID NO: 6398

GTTTCCCAGTAGGTCTC N ACATCC SEQ ID NO: 6399

GTTTCCCAGTAGGTCTC N ACATGA SEQ ID NO: 6400

GTTTCCCAGTAGGTCTC N ACATTT SEQ ID NO: 6401

GTTTCCCAGTAGGTCTC N ACCAAT SEQ ID NO: 6402

GTTTCCCAGTAGGTCTC N ACCACG SEQ ID NO: 6403

GTTTCCCAGTAGGTCTC N ACCACT SEQ ID NO: 6404

GTTTCCCAGTAGGTCTC N ACCAGG SEQ ID NO: 6405

GTTTCCCAGTAGGTCTC N ACCATT SEQ ID NO: 6406

GTTTCCCAGTAGGTCTC N ACCCCC SEQ ID NO: 6407

GTTTCCCAGTAGGTCTC N ACCCCT SEQ ID NO: 6408

GTTTCCCAGTAGGTCTC N ACCGAA SEQ ID NO: 6409

GTTTCCCAGTAGGTCTC N ACCGGT SEQ ID NO: 6410

GTTTCCCAGTAGGTCTC N ACCGTA SEQ ID NO: 641 1

GTTTCCCAGTAGGTCTC N ACCTAG SEQ ID NO: 6412

GTTTCCCAGTAGGTCTC N ACCTCG SEQ ID NO: 6413

GTTTCCCAGTAGGTCTC N ACCTGA SEQ ID NO: 6414

GTTTCCCAGTAGGTCTC N ACGAAG SEQ ID NO: 6415

GTTTCCCAGTAGGTCTC N ACGACA SEQ ID NO: 6416

GTTTCCCAGTAGGTCTC N ACGAGA SEQ ID NO: 6417

GTTTCCCAGTAGGTCTC N ACGAGC SEQ ID NO: 6418

GTTTCCCAGTAGGTCTC N ACGAGT SEQ ID NO: 6419

GTTTCCCAGTAGGTCTC N ACGATA SEQ ID NO: 6420 G I N CCCAGTAGGTCTC N ACGATC SEQ ID NO: 6421

GTTTCCCAGTAGGTCTC N ACGATG SEQ ID NO: 6422

GTTTCCCAGTAGGTCTC N ACGATT SEQ ID NO: 6423

GTTTCCCAGTAGGTCTC N ACGCGA SEQ ID NO: 6424

GTTTCCCAGTAGGTCTC N ACGCGG SEQ ID NO: 6425

GTTTCCCAGTAGGTCTC N ACGCGT SEQ ID NO: 6426

GTTTCCCAGTAGGTCTC N ACGCTA SEQ ID NO: 6427

GTTTCCCAGTAGGTCTC N ACGGCA SEQ ID NO: 6428

GTTTCCCAGTAGGTCTC N ACGGCT SEQ ID NO: 6429

GTTTCCCAGTAGGTCTC N ACGGTG SEQ ID NO: 6430

GTTTCCCAGTAGGTCTC N ACGTAA SEQ ID NO: 6431

GTTTCCCAGTAGGTCTC N ACGTAC SEQ ID NO: 6432

GTTTCCCAGTAGGTCTC N ACGTAT SEQ ID NO: 6433

GTTTCCCAGTAGGTCTC N ACGTCC SEQ ID NO: 6434

GTTTCCCAGTAGGTCTC N ACGTGA SEQ ID NO: 6435

GTTTCCCAGTAGGTCTC N ACGTGT SEQ ID NO: 6436

GTTTCCCAGTAGGTCTC N ACGTTA SEQ ID NO: 6437

GTTTCCCAGTAGGTCTC N ACGTTG SEQ ID NO: 6438

GTTTCCCAGTAGGTCTC N ACTACA SEQ ID NO: 6439

GTTTCCCAGTAGGTCTC N ACTACT SEQ ID NO: 6440

GTTTCCCAGTAGGTCTC N ACTAGC SEQ ID NO: 6441

GTTTCCCAGTAGGTCTC N ACTCAA SEQ ID NO: 6442

GTTTCCCAGTAGGTCTC N ACTCCA SEQ ID NO: 6443

GTTTCCCAGTAGGTCTC N ACTCGA SEQ ID NO: 6444

GTTTCCCAGTAGGTCTC N ACTCGT SEQ ID NO: 6445

GTTTCCCAGTAGGTCTC N ACTCTG SEQ ID NO: 6446

GTTTCCCAGTAGGTCTC N ACTGAT SEQ ID NO: 6447

GTTTCCCAGTAGGTCTC N ACTGCA SEQ ID NO: 6448

GTTTCCCAGTAGGTCTC N ACTGGC SEQ ID NO: 6449

GTTTCCCAGTAGGTCTC N ACTGTA SEQ ID NO: 6450

GTTTCCCAGTAGGTCTC N ACTGTC SEQ ID NO: 6451

GTTTCCCAGTAGGTCTC N ACTTCA SEQ ID NO: 6452

GTTTCCCAGTAGGTCTC N ACTTCT SEQ ID NO: 6453

GTTTCCCAGTAGGTCTC N AGAAGC SEQ ID NO: 6454

GTTTCCCAGTAGGTCTC N AGAATC SEQ ID NO: 6455

GTTTCCCAGTAGGTCTC N AGACAC SEQ ID NO: 6456

GTTTCCCAGTAGGTCTC N AGACAG SEQ ID NO: 6457

GTTTCCCAGTAGGTCTC N AGACAT SEQ ID NO: 6458

GTTTCCCAGTAGGTCTC N AGACCA SEQ ID NO: 6459

GTTTCCCAGTAGGTCTC N AGACCG SEQ ID NO: 6460

GTTTCCCAGTAGGTCTC N AGACGA SEQ ID NO: 6461

GTTTCCCAGTAGGTCTC N AGACGC SEQ ID NO: 6462

GTTTCCCAGTAGGTCTC N AGACTC SEQ ID NO: 6463 G I N CCCAGTAGGTCTC N AGACTG SEQ ID NO: 6464

GTTTCCCAGTAGGTCTC N AGAGAC SEQ ID NO: 6465

GTTTCCCAGTAGGTCTC N AGATAA SEQ ID NO: 6466

GTTTCCCAGTAGGTCTC N AGATAC SEQ ID NO: 6467

GTTTCCCAGTAGGTCTC N AGATCC SEQ ID NO: 6468

GTTTCCCAGTAGGTCTC N AGATGC SEQ ID NO: 6469

GTTTCCCAGTAGGTCTC N AGATGT SEQ ID NO: 6470

GTTTCCCAGTAGGTCTC N AGATTA SEQ ID NO: 6471

GTTTCCCAGTAGGTCTC N AGATTC SEQ ID NO: 6472

GTTTCCCAGTAGGTCTC N AGCAAA SEQ ID NO: 6473

GTTTCCCAGTAGGTCTC N AGCAAT SEQ ID NO: 6474

GTTTCCCAGTAGGTCTC N AGCACG SEQ ID NO: 6475

GTTTCCCAGTAGGTCTC N AGCAGA SEQ ID NO: 6476

GTTTCCCAGTAGGTCTC N AGCAGC SEQ ID NO: 6477

GTTTCCCAGTAGGTCTC N AGCATT SEQ ID NO: 6478

GTTTCCCAGTAGGTCTC N AGCCAT SEQ ID NO: 6479

GTTTCCCAGTAGGTCTC N AGCCTC SEQ ID NO: 6480

GTTTCCCAGTAGGTCTC N AGCCTG SEQ ID NO: 6481

GTTTCCCAGTAGGTCTC N AGCGCA SEQ ID NO: 6482

GTTTCCCAGTAGGTCTC N AGCGGT SEQ ID NO: 6483

GTTTCCCAGTAGGTCTC N AGCGTA SEQ ID NO: 6484

GTTTCCCAGTAGGTCTC N AGCGTG SEQ ID NO: 6485

GTTTCCCAGTAGGTCTC N AGCTCC SEQ ID NO: 6486

GTTTCCCAGTAGGTCTC N AGGAAA SEQ ID NO: 6487

GTTTCCCAGTAGGTCTC N AGGAAC SEQ ID NO: 6488

GTTTCCCAGTAGGTCTC N AGGACG SEQ ID NO: 6489

GTTTCCCAGTAGGTCTC N AGGAGC SEQ ID NO: 6490

GTTTCCCAGTAGGTCTC N AGGCCG SEQ ID NO: 6491

GTTTCCCAGTAGGTCTC N AGGTAA SEQ ID NO: 6492

GTTTCCCAGTAGGTCTC N AGGTAC SEQ ID NO: 6493

GTTTCCCAGTAGGTCTC N AGGTCT SEQ ID NO: 6494

GTTTCCCAGTAGGTCTC N AGGTGC SEQ ID NO: 6495

GTTTCCCAGTAGGTCTC N AGTAAC SEQ ID NO: 6496

GTTTCCCAGTAGGTCTC N AGTAAT SEQ ID NO: 6497

GTTTCCCAGTAGGTCTC N AGTACC SEQ ID NO: 6498

GTTTCCCAGTAGGTCTC N AGTACG SEQ ID NO: 6499

GTTTCCCAGTAGGTCTC N AGTATC SEQ ID NO: 6500

GTTTCCCAGTAGGTCTC N AGTATT SEQ ID NO: 6501

GTTTCCCAGTAGGTCTC N AGTCCA SEQ ID NO: 6502

GTTTCCCAGTAGGTCTC N AGTCCC SEQ ID NO: 6503

GTTTCCCAGTAGGTCTC N AGTCGA SEQ ID NO: 6504

GTTTCCCAGTAGGTCTC N AGTCGC SEQ ID NO: 6505

GTTTCCCAGTAGGTCTC N AGTCGT SEQ ID NO: 6506 G I N CCCAGTAGGTCTC N AGTCTG SEQ ID NO: 6507

GTTTCCCAGTAGGTCTC N AGTGAA SEQ ID NO: 6508

GTTTCCCAGTAGGTCTC N AGTGAC SEQ ID NO: 6509

GTTTCCCAGTAGGTCTC N AGTGAT SEQ ID NO: 6510

GTTTCCCAGTAGGTCTC N AGTGCC SEQ ID NO: 651 1

GTTTCCCAGTAGGTCTC N AGTGCT SEQ ID NO: 6512

GTTTCCCAGTAGGTCTC N AGTGGT SEQ ID NO: 6513

GTTTCCCAGTAGGTCTC N AGTTCG SEQ ID NO: 6514

GTTTCCCAGTAGGTCTC N AGTTGC SEQ ID NO: 6515

GTTTCCCAGTAGGTCTC N ATAAAC SEQ ID NO: 6516

GTTTCCCAGTAGGTCTC N ATAAAG SEQ ID NO: 6517

GTTTCCCAGTAGGTCTC N ATAACA SEQ ID NO: 6518

GTTTCCCAGTAGGTCTC N ATAACC SEQ ID NO: 6519

GTTTCCCAGTAGGTCTC N ATAACT SEQ ID NO: 6520

GTTTCCCAGTAGGTCTC N ATAAGC SEQ ID NO: 6521

GTTTCCCAGTAGGTCTC N ATACAA SEQ ID NO: 6522

GTTTCCCAGTAGGTCTC N ATACAG SEQ ID NO: 6523

GTTTCCCAGTAGGTCTC N ATACAT SEQ ID NO: 6524

GTTTCCCAGTAGGTCTC N ATACCG SEQ ID NO: 6525

GTTTCCCAGTAGGTCTC N ATACCT SEQ ID NO: 6526

GTTTCCCAGTAGGTCTC N ATACGC SEQ ID NO: 6527

GTTTCCCAGTAGGTCTC N ATACGG SEQ ID NO: 6528

GTTTCCCAGTAGGTCTC N ATACGT SEQ ID NO: 6529

GTTTCCCAGTAGGTCTC N ATAGCA SEQ ID NO: 6530

GTTTCCCAGTAGGTCTC N ATAGTC SEQ ID NO: 6531

GTTTCCCAGTAGGTCTC N ATATAC SEQ ID NO: 6532

GTTTCCCAGTAGGTCTC N ATATCC SEQ ID NO: 6533

GTTTCCCAGTAGGTCTC N ATATCG SEQ ID NO: 6534

GTTTCCCAGTAGGTCTC N ATATTC SEQ ID NO: 6535

GTTTCCCAGTAGGTCTC N ATCACC SEQ ID NO: 6536

GTTTCCCAGTAGGTCTC N ATCAGC SEQ ID NO: 6537

GTTTCCCAGTAGGTCTC N ATCATA SEQ ID NO: 6538

GTTTCCCAGTAGGTCTC N ATCCGT SEQ ID NO: 6539

GTTTCCCAGTAGGTCTC N ATCGAC SEQ ID NO: 6540

GTTTCCCAGTAGGTCTC N ATCGCA SEQ ID NO: 6541

GTTTCCCAGTAGGTCTC N ATCTAC SEQ ID NO: 6542

GTTTCCCAGTAGGTCTC N ATCTCA SEQ ID NO: 6543

GTTTCCCAGTAGGTCTC N ATCTGG SEQ ID NO: 6544

GTTTCCCAGTAGGTCTC N ATCTTC SEQ ID NO: 6545

GTTTCCCAGTAGGTCTC N ATCTTG SEQ ID NO: 6546

GTTTCCCAGTAGGTCTC N ATGACA SEQ ID NO: 6547

GTTTCCCAGTAGGTCTC N ATGAGG SEQ ID NO: 6548

GTTTCCCAGTAGGTCTC N ATGCAA SEQ ID NO: 6549 G I N CCCAGTAGGTCTC N ATGCAT SEQ ID NO: 6550

GTTTCCCAGTAGGTCTC N ATGCCG SEQ ID NO: 6551

GTTTCCCAGTAGGTCTC N ATGCGA SEQ ID NO: 6552

GTTTCCCAGTAGGTCTC N ATGCTC SEQ ID NO: 6553

GTTTCCCAGTAGGTCTC N ATGCTG SEQ ID NO: 6554

GTTTCCCAGTAGGTCTC N ATGGAC SEQ ID NO: 6555

GTTTCCCAGTAGGTCTC N ATGGTG SEQ ID NO: 6556

GTTTCCCAGTAGGTCTC N ATGTAA SEQ ID NO: 6557

GTTTCCCAGTAGGTCTC N ATGTAC SEQ ID NO: 6558

GTTTCCCAGTAGGTCTC N ATGTCA SEQ ID NO: 6559

GTTTCCCAGTAGGTCTC N ATGTCG SEQ ID NO: 6560

GTTTCCCAGTAGGTCTC N ATGTGC SEQ ID NO: 6561

GTTTCCCAGTAGGTCTC N ATGTTG SEQ ID NO: 6562

GTTTCCCAGTAGGTCTC N ATTACG SEQ ID NO: 6563

GTTTCCCAGTAGGTCTC N ATTATC SEQ ID NO: 6564

GTTTCCCAGTAGGTCTC N ATTCAA SEQ ID NO: 6565

GTTTCCCAGTAGGTCTC N ATTCAC SEQ ID NO: 6566

GTTTCCCAGTAGGTCTC N ATTCGA SEQ ID NO: 6567

GTTTCCCAGTAGGTCTC N ATTCTC SEQ ID NO: 6568

GTTTCCCAGTAGGTCTC N ATTGAT SEQ ID NO: 6569

GTTTCCCAGTAGGTCTC N ATTGCC SEQ ID NO: 6570

GTTTCCCAGTAGGTCTC N ATTGGA SEQ ID NO: 6571

GTTTCCCAGTAGGTCTC N ATTTCC SEQ ID NO: 6572

GTTTCCCAGTAGGTCTC N ATTTCG SEQ ID NO: 6573

GTTTCCCAGTAGGTCTC N ATTTTA SEQ ID NO: 6574

GTTTCCCAGTAGGTCTC N CAAAAC SEQ ID NO: 6575

GTTTCCCAGTAGGTCTC N CAAACA SEQ ID NO: 6576

GTTTCCCAGTAGGTCTC N CAAATA SEQ ID NO: 6577

GTTTCCCAGTAGGTCTC N CAACCT SEQ ID NO: 6578

GTTTCCCAGTAGGTCTC N CAACGA SEQ ID NO: 6579

GTTTCCCAGTAGGTCTC N CAACGT SEQ ID NO: 6580

GTTTCCCAGTAGGTCTC N CAAGGA SEQ ID NO: 6581

GTTTCCCAGTAGGTCTC N CAAGTC SEQ ID NO: 6582

GTTTCCCAGTAGGTCTC N CAAGTT SEQ ID NO: 6583

GTTTCCCAGTAGGTCTC N CAATAT SEQ ID NO: 6584

GTTTCCCAGTAGGTCTC N CAATCA SEQ ID NO: 6585

GTTTCCCAGTAGGTCTC N CAATGC SEQ ID NO: 6586

GTTTCCCAGTAGGTCTC N CAATGT SEQ ID NO: 6587

GTTTCCCAGTAGGTCTC N CACAAC SEQ ID NO: 6588

GTTTCCCAGTAGGTCTC N CACACA SEQ ID NO: 6589

GTTTCCCAGTAGGTCTC N CACAGC SEQ ID NO: 6590

GTTTCCCAGTAGGTCTC N CACAGG SEQ ID NO: 6591

GTTTCCCAGTAGGTCTC N CACAGT SEQ ID NO: 6592 G I N CCCAGTAGGTCTC N CACATT SEQ ID NO: 6593

GTTTCCCAGTAGGTCTC N CACCCC SEQ ID NO: 6594

GTTTCCCAGTAGGTCTC N CACCGA SEQ ID NO: 6595

GTTTCCCAGTAGGTCTC N CACCTA SEQ ID NO: 6596

GTTTCCCAGTAGGTCTC N CACGAG SEQ ID NO: 6597

GTTTCCCAGTAGGTCTC N CACGAT SEQ ID NO: 6598

GTTTCCCAGTAGGTCTC N CACTGA SEQ ID NO: 6599

GTTTCCCAGTAGGTCTC N CAGAAT SEQ ID NO: 6600

GTTTCCCAGTAGGTCTC N CAGAGA SEQ ID NO: 6601

GTTTCCCAGTAGGTCTC N CAGCAA SEQ ID NO: 6602

GTTTCCCAGTAGGTCTC N CAGCAC SEQ ID NO: 6603

GTTTCCCAGTAGGTCTC N CAGCAG SEQ ID NO: 6604

GTTTCCCAGTAGGTCTC N CAGCAT SEQ ID NO: 6605

GTTTCCCAGTAGGTCTC N CAGCCT SEQ ID NO: 6606

GTTTCCCAGTAGGTCTC N CAGCGT SEQ ID NO: 6607

GTTTCCCAGTAGGTCTC N CAGCTG SEQ ID NO: 6608

GTTTCCCAGTAGGTCTC N CAGGAA SEQ ID NO: 6609

GTTTCCCAGTAGGTCTC N CAGGCC SEQ ID NO: 6610

GTTTCCCAGTAGGTCTC N CAGGTA SEQ ID NO: 661 1

GTTTCCCAGTAGGTCTC N CAGTAA SEQ ID NO: 6612

GTTTCCCAGTAGGTCTC N CAGTAT SEQ ID NO: 6613

GTTTCCCAGTAGGTCTC N CAGTCC SEQ ID NO: 6614

GTTTCCCAGTAGGTCTC N CAGTCT SEQ ID NO: 6615

GTTTCCCAGTAGGTCTC N CAGTGC SEQ ID NO: 6616

GTTTCCCAGTAGGTCTC N CAGTTG SEQ ID NO: 6617

GTTTCCCAGTAGGTCTC N CATAAA SEQ ID NO: 6618

GTTTCCCAGTAGGTCTC N CATAAC SEQ ID NO: 6619

GTTTCCCAGTAGGTCTC N CATACC SEQ ID NO: 6620

GTTTCCCAGTAGGTCTC N CATACG SEQ ID NO: 6621

GTTTCCCAGTAGGTCTC N CATAGG SEQ ID NO: 6622

GTTTCCCAGTAGGTCTC N CATATA SEQ ID NO: 6623

GTTTCCCAGTAGGTCTC N CATATC SEQ ID NO: 6624

GTTTCCCAGTAGGTCTC N CATATG SEQ ID NO: 6625

GTTTCCCAGTAGGTCTC N CATCAA SEQ ID NO: 6626

GTTTCCCAGTAGGTCTC N CATCCG SEQ ID NO: 6627

GTTTCCCAGTAGGTCTC N CATCTG SEQ ID NO: 6628

GTTTCCCAGTAGGTCTC N CATGAA SEQ ID NO: 6629

GTTTCCCAGTAGGTCTC N CATGAC SEQ ID NO: 6630

GTTTCCCAGTAGGTCTC N CATGAG SEQ ID NO: 6631

GTTTCCCAGTAGGTCTC N CATGAT SEQ ID NO: 6632

GTTTCCCAGTAGGTCTC N CATGCT SEQ ID NO: 6633

GTTTCCCAGTAGGTCTC N CATTAA SEQ ID NO: 6634

GTTTCCCAGTAGGTCTC N CATTAC SEQ ID NO: 6635 G I N CCCAGTAGGTCTC N CCAATA SEQ ID NO: 6636

GTTTCCCAGTAGGTCTC N CCACAT SEQ ID NO: 6637

GTTTCCCAGTAGGTCTC N CCACGT SEQ ID NO: 6638

GTTTCCCAGTAGGTCTC N CCACTG SEQ ID NO: 6639

GTTTCCCAGTAGGTCTC N CCAGAA SEQ ID NO: 6640

GTTTCCCAGTAGGTCTC N CCAGAT SEQ ID NO: 6641

GTTTCCCAGTAGGTCTC N CCAGCA SEQ ID NO: 6642

GTTTCCCAGTAGGTCTC N CCAGGA SEQ ID NO: 6643

GTTTCCCAGTAGGTCTC N CCAGTG SEQ ID NO: 6644

GTTTCCCAGTAGGTCTC N CCATAA SEQ ID NO: 6645

GTTTCCCAGTAGGTCTC N C CAT AT SEQ ID NO: 6646

GTTTCCCAGTAGGTCTC N CCATGA SEQ ID NO: 6647

GTTTCCCAGTAGGTCTC N CCCAAC SEQ ID NO: 6648

GTTTCCCAGTAGGTCTC N CCCAAT SEQ ID NO: 6649

GTTTCCCAGTAGGTCTC N CCCAGA SEQ ID NO: 6650

GTTTCCCAGTAGGTCTC N CCCATA SEQ ID NO: 6651

GTTTCCCAGTAGGTCTC N CCCCCT SEQ ID NO: 6652

GTTTCCCAGTAGGTCTC N CCCCTT SEQ ID NO: 6653

GTTTCCCAGTAGGTCTC N CCCGGT SEQ ID NO: 6654

GTTTCCCAGTAGGTCTC N CCCGTA SEQ ID NO: 6655

GTTTCCCAGTAGGTCTC N CCCTAA SEQ ID NO: 6656

GTTTCCCAGTAGGTCTC N CCCTAC SEQ ID NO: 6657

GTTTCCCAGTAGGTCTC N CCCTAG SEQ ID NO: 6658

GTTTCCCAGTAGGTCTC N CCCTCA SEQ ID NO: 6659

GTTTCCCAGTAGGTCTC N CCGAAC SEQ ID NO: 6660

GTTTCCCAGTAGGTCTC N CCGAAT SEQ ID NO: 6661

GTTTCCCAGTAGGTCTC N CCGAGC SEQ ID NO: 6662

GTTTCCCAGTAGGTCTC N CCGATA SEQ ID NO: 6663

GTTTCCCAGTAGGTCTC N CCGATG SEQ ID NO: 6664

GTTTCCCAGTAGGTCTC N CCGCAA SEQ ID NO: 6665

GTTTCCCAGTAGGTCTC N CCGCGT SEQ ID NO: 6666

GTTTCCCAGTAGGTCTC N CCGGCA SEQ ID NO: 6667

GTTTCCCAGTAGGTCTC N CCGGTT SEQ ID NO: 6668

GTTTCCCAGTAGGTCTC N CCGTAC SEQ ID NO: 6669

GTTTCCCAGTAGGTCTC N CCGTAG SEQ ID NO: 6670

GTTTCCCAGTAGGTCTC N CCGTGA SEQ ID NO: 6671

GTTTCCCAGTAGGTCTC N CCGTTG SEQ ID NO: 6672

GTTTCCCAGTAGGTCTC N CCTAAA SEQ ID NO: 6673

GTTTCCCAGTAGGTCTC N CCTAAG SEQ ID NO: 6674

GTTTCCCAGTAGGTCTC N CCTAAT SEQ ID NO: 6675

GTTTCCCAGTAGGTCTC N CCTACC SEQ ID NO: 6676

GTTTCCCAGTAGGTCTC N CCTACG SEQ ID NO: 6677

GTTTCCCAGTAGGTCTC N CCTAGA SEQ ID NO: 6678 G I N CCCAGTAGGTCTC N CCTATC SEQ ID NO: 6679

GTTTCCCAGTAGGTCTC N CCTGAA SEQ ID NO: 6680

GTTTCCCAGTAGGTCTC N CCTGAC SEQ ID NO: 6681

GTTTCCCAGTAGGTCTC N CCTGCA SEQ ID NO: 6682

GTTTCCCAGTAGGTCTC N CCTGGC SEQ ID NO: 6683

GTTTCCCAGTAGGTCTC N CGAAAC SEQ ID NO: 6684

GTTTCCCAGTAGGTCTC N CGAACG SEQ ID NO: 6685

GTTTCCCAGTAGGTCTC N CGAACT SEQ ID NO: 6686

GTTTCCCAGTAGGTCTC N CGAAGA SEQ ID NO: 6687

GTTTCCCAGTAGGTCTC N CGAAGC SEQ ID NO: 6688

GTTTCCCAGTAGGTCTC N CGAATA SEQ ID NO: 6689

GTTTCCCAGTAGGTCTC N CGAATC SEQ ID NO: 6690

GTTTCCCAGTAGGTCTC N CGACAA SEQ ID NO: 6691

GTTTCCCAGTAGGTCTC N CGACAG SEQ ID NO: 6692

GTTTCCCAGTAGGTCTC N CGACCA SEQ ID NO: 6693

GTTTCCCAGTAGGTCTC N CGACGA SEQ ID NO: 6694

GTTTCCCAGTAGGTCTC N CGAGCG SEQ ID NO: 6695

GTTTCCCAGTAGGTCTC N CGAGTA SEQ ID NO: 6696

GTTTCCCAGTAGGTCTC N CGAGTC SEQ ID NO: 6697

GTTTCCCAGTAGGTCTC N CGAGTG SEQ ID NO: 6698

GTTTCCCAGTAGGTCTC N CGATAA SEQ ID NO: 6699

GTTTCCCAGTAGGTCTC N CGATAC SEQ ID NO: 6700

GTTTCCCAGTAGGTCTC N CGATAG SEQ ID NO: 6701

GTTTCCCAGTAGGTCTC N C GAT AT SEQ ID NO: 6702

GTTTCCCAGTAGGTCTC N CGATCT SEQ ID NO: 6703

GTTTCCCAGTAGGTCTC N CGATGT SEQ ID NO: 6704

GTTTCCCAGTAGGTCTC N CGATTC SEQ ID NO: 6705

GTTTCCCAGTAGGTCTC N CGATTG SEQ ID NO: 6706

GTTTCCCAGTAGGTCTC N CGCAAA SEQ ID NO: 6707

GTTTCCCAGTAGGTCTC N CGCAAC SEQ ID NO: 6708

GTTTCCCAGTAGGTCTC N CGCACG SEQ ID NO: 6709

GTTTCCCAGTAGGTCTC N CGCAGA SEQ ID NO: 6710

GTTTCCCAGTAGGTCTC N CGCAGT SEQ ID NO: 671 1

GTTTCCCAGTAGGTCTC N CGCATA SEQ ID NO: 6712

GTTTCCCAGTAGGTCTC N CGCATG SEQ ID NO: 6713

GTTTCCCAGTAGGTCTC N CGCGCA SEQ ID NO: 6714

GTTTCCCAGTAGGTCTC N CGCTAA SEQ ID NO: 6715

GTTTCCCAGTAGGTCTC N CGCTAG SEQ ID NO: 6716

GTTTCCCAGTAGGTCTC N CGCTGT SEQ ID NO: 6717

GTTTCCCAGTAGGTCTC N CGGAAA SEQ ID NO: 6718

GTTTCCCAGTAGGTCTC N CGGAGC SEQ ID NO: 6719

GTTTCCCAGTAGGTCTC N CGGAGT SEQ ID NO: 6720

GTTTCCCAGTAGGTCTC N CGGATG SEQ ID NO: 6721 G I N CCCAGTAGGTCTC N CGGCAC SEQ ID NO: 6722

GTTTCCCAGTAGGTCTC N CGGGCA SEQ ID NO: 6723

GTTTCCCAGTAGGTCTC N CGGTAA SEQ ID NO: 6724

GTTTCCCAGTAGGTCTC N CGGTCA SEQ ID NO: 6725

GTTTCCCAGTAGGTCTC N CGGTGA SEQ ID NO: 6726

GTTTCCCAGTAGGTCTC N CGGTTA SEQ ID NO: 6727

GTTTCCCAGTAGGTCTC N CGTAAG SEQ ID NO: 6728

GTTTCCCAGTAGGTCTC N CGTAAT SEQ ID NO: 6729

GTTTCCCAGTAGGTCTC N CGTACC SEQ ID NO: 6730

GTTTCCCAGTAGGTCTC N CGTACG SEQ ID NO: 6731

GTTTCCCAGTAGGTCTC N CGTAGA SEQ ID NO: 6732

GTTTCCCAGTAGGTCTC N CGTATA SEQ ID NO: 6733

GTTTCCCAGTAGGTCTC N CGTATG SEQ ID NO: 6734

GTTTCCCAGTAGGTCTC N CGTCAT SEQ ID NO: 6735

GTTTCCCAGTAGGTCTC N CGTCCG SEQ ID NO: 6736

GTTTCCCAGTAGGTCTC N CGTCGA SEQ ID NO: 6737

GTTTCCCAGTAGGTCTC N CGTCGT SEQ ID NO: 6738

GTTTCCCAGTAGGTCTC N CGTCTA SEQ ID NO: 6739

GTTTCCCAGTAGGTCTC N CGTCTC SEQ ID NO: 6740

GTTTCCCAGTAGGTCTC N CGTGAA SEQ ID NO: 6741

GTTTCCCAGTAGGTCTC N CGTGAC SEQ ID NO: 6742

GTTTCCCAGTAGGTCTC N CGTGAT SEQ ID NO: 6743

GTTTCCCAGTAGGTCTC N CGTGGA SEQ ID NO: 6744

GTTTCCCAGTAGGTCTC N CGTGTA SEQ ID NO: 6745

GTTTCCCAGTAGGTCTC N CGTTAG SEQ ID NO: 6746

GTTTCCCAGTAGGTCTC N CGTTGC SEQ ID NO: 6747

GTTTCCCAGTAGGTCTC N CGTTGG SEQ ID NO: 6748

GTTTCCCAGTAGGTCTC N CGTTGT SEQ ID NO: 6749

GTTTCCCAGTAGGTCTC N CTAACT SEQ ID NO: 6750

GTTTCCCAGTAGGTCTC N CTAATG SEQ ID NO: 6751

GTTTCCCAGTAGGTCTC N CTACAG SEQ ID NO: 6752

GTTTCCCAGTAGGTCTC N CTACCC SEQ ID NO: 6753

GTTTCCCAGTAGGTCTC N CTACGC SEQ ID NO: 6754

GTTTCCCAGTAGGTCTC N CTACGT SEQ ID NO: 6755

GTTTCCCAGTAGGTCTC N CTACTG SEQ ID NO: 6756

GTTTCCCAGTAGGTCTC N CTACTT SEQ ID NO: 6757

GTTTCCCAGTAGGTCTC N CTAGAC SEQ ID NO: 6758

GTTTCCCAGTAGGTCTC N CTAGCA SEQ ID NO: 6759

GTTTCCCAGTAGGTCTC N CTAGCC SEQ ID NO: 6760

GTTTCCCAGTAGGTCTC N CTATCT SEQ ID NO: 6761

GTTTCCCAGTAGGTCTC N CTATGC SEQ ID NO: 6762

GTTTCCCAGTAGGTCTC N CTCAAA SEQ ID NO: 6763

GTTTCCCAGTAGGTCTC N CTCAAG SEQ ID NO: 6764 G I N CCCAGTAGGTCTC N CTCATC SEQ ID NO: 6765

GTTTCCCAGTAGGTCTC N CTCCAT SEQ ID NO: 6766

GTTTCCCAGTAGGTCTC N CTCCGT SEQ ID NO: 6767

GTTTCCCAGTAGGTCTC N CTCCTA SEQ ID NO: 6768

GTTTCCCAGTAGGTCTC N CTCGAG SEQ ID NO: 6769

GTTTCCCAGTAGGTCTC N CTCGCT SEQ ID NO: 6770

GTTTCCCAGTAGGTCTC N CTCGGA SEQ ID NO: 6771

GTTTCCCAGTAGGTCTC N CTCGGT SEQ ID NO: 6772

GTTTCCCAGTAGGTCTC N CTCTGA SEQ ID NO: 6773

GTTTCCCAGTAGGTCTC N CTCTGC SEQ ID NO: 6774

GTTTCCCAGTAGGTCTC N CTCTGT SEQ ID NO: 6775

GTTTCCCAGTAGGTCTC N CTGAGA SEQ ID NO: 6776

GTTTCCCAGTAGGTCTC N CTGAGT SEQ ID NO: 6777

GTTTCCCAGTAGGTCTC N CTGCAA SEQ ID NO: 6778

GTTTCCCAGTAGGTCTC N CTGCAG SEQ ID NO: 6779

GTTTCCCAGTAGGTCTC N CTGCCA SEQ ID NO: 6780

GTTTCCCAGTAGGTCTC N CTGGCC SEQ ID NO: 6781

GTTTCCCAGTAGGTCTC N CTGGGA SEQ ID NO: 6782

GTTTCCCAGTAGGTCTC N CTGTAA SEQ ID NO: 6783

GTTTCCCAGTAGGTCTC N CTGTAC SEQ ID NO: 6784

GTTTCCCAGTAGGTCTC N CTGTAG SEQ ID NO: 6785

GTTTCCCAGTAGGTCTC N CTGTCG SEQ ID NO: 6786

GTTTCCCAGTAGGTCTC N CTGTGA SEQ ID NO: 6787

GTTTCCCAGTAGGTCTC N CTTACA SEQ ID NO: 6788

GTTTCCCAGTAGGTCTC N CTTCGT SEQ ID NO: 6789

GTTTCCCAGTAGGTCTC N CTTGTA SEQ ID NO: 6790

GTTTCCCAGTAGGTCTC N GAAAAA SEQ ID NO: 6791

GTTTCCCAGTAGGTCTC N GAAACA SEQ ID NO: 6792

GTTTCCCAGTAGGTCTC N GAAACG SEQ ID NO: 6793

GTTTCCCAGTAGGTCTC N GAAATG SEQ ID NO: 6794

GTTTCCCAGTAGGTCTC N GAACGA SEQ ID NO: 6795

GTTTCCCAGTAGGTCTC N GAACGT SEQ ID NO: 6796

GTTTCCCAGTAGGTCTC N GAACTT SEQ ID NO: 6797

GTTTCCCAGTAGGTCTC N GAAGCC SEQ ID NO: 6798

GTTTCCCAGTAGGTCTC N GAAGTC SEQ ID NO: 6799

GTTTCCCAGTAGGTCTC N GAATAC SEQ ID NO: 6800

GTTTCCCAGTAGGTCTC N GAATCA SEQ ID NO: 6801

GTTTCCCAGTAGGTCTC N GAATTG SEQ ID NO: 6802

GTTTCCCAGTAGGTCTC N GACAAC SEQ ID NO: 6803

GTTTCCCAGTAGGTCTC N GACAAG SEQ ID NO: 6804

GTTTCCCAGTAGGTCTC N GACAAT SEQ ID NO: 6805

GTTTCCCAGTAGGTCTC N GACACA SEQ ID NO: 6806

GTTTCCCAGTAGGTCTC N GACAGA SEQ ID NO: 6807 G I N CCCAGTAGGTCTC N GACAGC SEQ ID NO: 6808

GTTTCCCAGTAGGTCTC N GACATA SEQ ID NO: 6809

GTTTCCCAGTAGGTCTC N GACCAC SEQ ID NO: 6810

GTTTCCCAGTAGGTCTC N GACCAG SEQ ID NO: 681 1

GTTTCCCAGTAGGTCTC N GACCAT SEQ ID NO: 6812

GTTTCCCAGTAGGTCTC N GACCTT SEQ ID NO: 6813

GTTTCCCAGTAGGTCTC N GACGAA SEQ ID NO: 6814

GTTTCCCAGTAGGTCTC N GACGAT SEQ ID NO: 6815

GTTTCCCAGTAGGTCTC N GACGCG SEQ ID NO: 6816

GTTTCCCAGTAGGTCTC N GACGGA SEQ ID NO: 6817

GTTTCCCAGTAGGTCTC N GACGTA SEQ ID NO: 6818

GTTTCCCAGTAGGTCTC N GACGTG SEQ ID NO: 6819

GTTTCCCAGTAGGTCTC N GACTCG SEQ ID NO: 6820

GTTTCCCAGTAGGTCTC N GACTCT SEQ ID NO: 6821

GTTTCCCAGTAGGTCTC N GACTGT SEQ ID NO: 6822

GTTTCCCAGTAGGTCTC N GAGACA SEQ ID NO: 6823

GTTTCCCAGTAGGTCTC N GAGACT SEQ ID NO: 6824

GTTTCCCAGTAGGTCTC N GAGCCC SEQ ID NO: 6825

GTTTCCCAGTAGGTCTC N GAGCGG SEQ ID NO: 6826

GTTTCCCAGTAGGTCTC N GAGGAC SEQ ID NO: 6827

GTTTCCCAGTAGGTCTC N GAGTAA SEQ ID NO: 6828

GTTTCCCAGTAGGTCTC N GAGTCG SEQ ID NO: 6829

GTTTCCCAGTAGGTCTC N GAGTGC SEQ ID NO: 6830

GTTTCCCAGTAGGTCTC N GAGTTA SEQ ID NO: 6831

GTTTCCCAGTAGGTCTC N GATAAC SEQ ID NO: 6832

GTTTCCCAGTAGGTCTC N GATACA SEQ ID NO: 6833

GTTTCCCAGTAGGTCTC N GATACC SEQ ID NO: 6834

GTTTCCCAGTAGGTCTC N GATACG SEQ ID NO: 6835

GTTTCCCAGTAGGTCTC N GATAGC SEQ ID NO: 6836

GTTTCCCAGTAGGTCTC N GATATA SEQ ID NO: 6837

GTTTCCCAGTAGGTCTC N GATCAT SEQ ID NO: 6838

GTTTCCCAGTAGGTCTC N GATCGA SEQ ID NO: 6839

GTTTCCCAGTAGGTCTC N GATCGC SEQ ID NO: 6840

GTTTCCCAGTAGGTCTC N GATCTC SEQ ID NO: 6841

GTTTCCCAGTAGGTCTC N GATCTT SEQ ID NO: 6842

GTTTCCCAGTAGGTCTC N GATGAA SEQ ID NO: 6843

GTTTCCCAGTAGGTCTC N GATGCA SEQ ID NO: 6844

GTTTCCCAGTAGGTCTC N GATGCC SEQ ID NO: 6845

GTTTCCCAGTAGGTCTC N GATGCG SEQ ID NO: 6846

GTTTCCCAGTAGGTCTC N GATGTA SEQ ID NO: 6847

GTTTCCCAGTAGGTCTC N GATTCA SEQ ID NO: 6848

GTTTCCCAGTAGGTCTC N GATTTC SEQ ID NO: 6849

GTTTCCCAGTAGGTCTC N GCAAAA SEQ ID NO: 6850 G I N CCCAGTAGGTCTC N GCAAAC SEQ ID NO: 6851

GTTTCCCAGTAGGTCTC N GCAACT SEQ ID NO: 6852

GTTTCCCAGTAGGTCTC N GCAATT SEQ ID NO: 6853

GTTTCCCAGTAGGTCTC N GCACAA SEQ ID NO: 6854

GTTTCCCAGTAGGTCTC N GCACAG SEQ ID NO: 6855

GTTTCCCAGTAGGTCTC N GCACCC SEQ ID NO: 6856

GTTTCCCAGTAGGTCTC N GCACTA SEQ ID NO: 6857

GTTTCCCAGTAGGTCTC N GCAGAG SEQ ID NO: 6858

GTTTCCCAGTAGGTCTC N GCAGAT SEQ ID NO: 6859

GTTTCCCAGTAGGTCTC N GCAGCA SEQ ID NO: 6860

GTTTCCCAGTAGGTCTC N GCAGCT SEQ ID NO: 6861

GTTTCCCAGTAGGTCTC N GCAGTA SEQ ID NO: 6862

GTTTCCCAGTAGGTCTC N GCAGTC SEQ ID NO: 6863

GTTTCCCAGTAGGTCTC N GCATAA SEQ ID NO: 6864

GTTTCCCAGTAGGTCTC N GCATAC SEQ ID NO: 6865

GTTTCCCAGTAGGTCTC N G CAT AT SEQ ID NO: 6866

GTTTCCCAGTAGGTCTC N GCATCT SEQ ID NO: 6867

GTTTCCCAGTAGGTCTC N GCATGA SEQ ID NO: 6868

GTTTCCCAGTAGGTCTC N GCATGG SEQ ID NO: 6869

GTTTCCCAGTAGGTCTC N GCATTA SEQ ID NO: 6870

GTTTCCCAGTAGGTCTC N GCCAAA SEQ ID NO: 6871

GTTTCCCAGTAGGTCTC N GCCATA SEQ ID NO: 6872

GTTTCCCAGTAGGTCTC N GCCATT SEQ ID NO: 6873

GTTTCCCAGTAGGTCTC N GCCCAA SEQ ID NO: 6874

GTTTCCCAGTAGGTCTC N GCCCTA SEQ ID NO: 6875

GTTTCCCAGTAGGTCTC N GCCGAA SEQ ID NO: 6876

GTTTCCCAGTAGGTCTC N GCCTAA SEQ ID NO: 6877

GTTTCCCAGTAGGTCTC N GCCTGA SEQ ID NO: 6878

GTTTCCCAGTAGGTCTC N GCCTTG SEQ ID NO: 6879

GTTTCCCAGTAGGTCTC N GCGACA SEQ ID NO: 6880

GTTTCCCAGTAGGTCTC N GCGACC SEQ ID NO: 6881

GTTTCCCAGTAGGTCTC N GCGAGT SEQ ID NO: 6882

GTTTCCCAGTAGGTCTC N GCGATA SEQ ID NO: 6883

GTTTCCCAGTAGGTCTC N GCGATT SEQ ID NO: 6884

GTTTCCCAGTAGGTCTC N GCGCAC SEQ ID NO: 6885

GTTTCCCAGTAGGTCTC N GCGCAG SEQ ID NO: 6886

GTTTCCCAGTAGGTCTC N GCGCAT SEQ ID NO: 6887

GTTTCCCAGTAGGTCTC N GCGCTA SEQ ID NO: 6888

GTTTCCCAGTAGGTCTC N GCGGAA SEQ ID NO: 6889

GTTTCCCAGTAGGTCTC N GCGGCC SEQ ID NO: 6890

GTTTCCCAGTAGGTCTC N GCGTAC SEQ ID NO: 6891

GTTTCCCAGTAGGTCTC N GCGTCC SEQ ID NO: 6892

GTTTCCCAGTAGGTCTC N GCGTCT SEQ ID NO: 6893 G I N CCCAGTAGGTCTC N GCGTGA SEQ ID NO: 6894

GTTTCCCAGTAGGTCTC N GCGTGT SEQ ID NO: 6895

GTTTCCCAGTAGGTCTC N GCTAAC SEQ ID NO: 6896

GTTTCCCAGTAGGTCTC N GCTAGC SEQ ID NO: 6897

GTTTCCCAGTAGGTCTC N GCTCGA SEQ ID NO: 6898

GTTTCCCAGTAGGTCTC N GCTGGT SEQ ID NO: 6899

GTTTCCCAGTAGGTCTC N GCTGTA SEQ ID NO: 6900

GTTTCCCAGTAGGTCTC N GCTTCC SEQ ID NO: 6901

GTTTCCCAGTAGGTCTC N GGAAAA SEQ ID NO: 6902

GTTTCCCAGTAGGTCTC N GGAAAG SEQ ID NO: 6903

GTTTCCCAGTAGGTCTC N GGAACA SEQ ID NO: 6904

GTTTCCCAGTAGGTCTC N GGACAA SEQ ID NO: 6905

GTTTCCCAGTAGGTCTC N GGACGT SEQ ID NO: 6906

GTTTCCCAGTAGGTCTC N G GAG AT SEQ ID NO: 6907

GTTTCCCAGTAGGTCTC N GGAGCA SEQ ID NO: 6908

GTTTCCCAGTAGGTCTC N GGAGCC SEQ ID NO: 6909

GTTTCCCAGTAGGTCTC N GGAGCG SEQ ID NO: 6910

GTTTCCCAGTAGGTCTC N GGAGCT SEQ ID NO: 691 1

GTTTCCCAGTAGGTCTC N GGCACC SEQ ID NO: 6912

GTTTCCCAGTAGGTCTC N GGCAGC SEQ ID NO: 6913

GTTTCCCAGTAGGTCTC N GGCGAT SEQ ID NO: 6914

GTTTCCCAGTAGGTCTC N GGCGTC SEQ ID NO: 6915

GTTTCCCAGTAGGTCTC N GGGAGA SEQ ID NO: 6916

GTTTCCCAGTAGGTCTC N GGGAGC SEQ ID NO: 6917

GTTTCCCAGTAGGTCTC N GGGCAC SEQ ID NO: 6918

GTTTCCCAGTAGGTCTC N GGTACA SEQ ID NO: 6919

GTTTCCCAGTAGGTCTC N GGTACC SEQ ID NO: 6920

GTTTCCCAGTAGGTCTC N GGTCAA SEQ ID NO: 6921

GTTTCCCAGTAGGTCTC N GGTCCC SEQ ID NO: 6922

GTTTCCCAGTAGGTCTC N GGTCGA SEQ ID NO: 6923

GTTTCCCAGTAGGTCTC N GGTGCA SEQ ID NO: 6924

GTTTCCCAGTAGGTCTC N GGTGGA SEQ ID NO: 6925

GTTTCCCAGTAGGTCTC N GGTGTC SEQ ID NO: 6926

GTTTCCCAGTAGGTCTC N GGTTGC SEQ ID NO: 6927

GTTTCCCAGTAGGTCTC N GTAACA SEQ ID NO: 6928

GTTTCCCAGTAGGTCTC N GTAACC SEQ ID NO: 6929

GTTTCCCAGTAGGTCTC N GTAACG SEQ ID NO: 6930

GTTTCCCAGTAGGTCTC N GTAAGT SEQ ID NO: 6931

GTTTCCCAGTAGGTCTC N GTAATG SEQ ID NO: 6932

GTTTCCCAGTAGGTCTC N GTACAT SEQ ID NO: 6933

GTTTCCCAGTAGGTCTC N GTACCA SEQ ID NO: 6934

GTTTCCCAGTAGGTCTC N GTACCC SEQ ID NO: 6935

GTTTCCCAGTAGGTCTC N GTACCT SEQ ID NO: 6936 G I N CCCAGTAGGTCTC N GTACGA SEQ ID NO: 6937

GTTTCCCAGTAGGTCTC N GTACGT SEQ ID NO: 6938

GTTTCCCAGTAGGTCTC N GTACTC SEQ ID NO: 6939

GTTTCCCAGTAGGTCTC N GTAGAC SEQ ID NO: 6940

GTTTCCCAGTAGGTCTC N GTAGAG SEQ ID NO: 6941

GTTTCCCAGTAGGTCTC N GTAGCA SEQ ID NO: 6942

GTTTCCCAGTAGGTCTC N GTATCA SEQ ID NO: 6943

GTTTCCCAGTAGGTCTC N GTATGT SEQ ID NO: 6944

GTTTCCCAGTAGGTCTC N GTCACA SEQ ID NO: 6945

GTTTCCCAGTAGGTCTC N GTCACG SEQ ID NO: 6946

GTTTCCCAGTAGGTCTC N GTCATC SEQ ID NO: 6947

GTTTCCCAGTAGGTCTC N GTCCAT SEQ ID NO: 6948

GTTTCCCAGTAGGTCTC N GTCCCA SEQ ID NO: 6949

GTTTCCCAGTAGGTCTC N GTCCCC SEQ ID NO: 6950

GTTTCCCAGTAGGTCTC N GTCCCG SEQ ID NO: 6951

GTTTCCCAGTAGGTCTC N GTCGAA SEQ ID NO: 6952

GTTTCCCAGTAGGTCTC N GTCGAC SEQ ID NO: 6953

GTTTCCCAGTAGGTCTC N GTCGAG SEQ ID NO: 6954

GTTTCCCAGTAGGTCTC N GTCGAT SEQ ID NO: 6955

GTTTCCCAGTAGGTCTC N GTCGCA SEQ ID NO: 6956

GTTTCCCAGTAGGTCTC N GTCGTG SEQ ID NO: 6957

GTTTCCCAGTAGGTCTC N GTCGTT SEQ ID NO: 6958

GTTTCCCAGTAGGTCTC N GTCTAC SEQ ID NO: 6959

GTTTCCCAGTAGGTCTC N GTCTAG SEQ ID NO: 6960

GTTTCCCAGTAGGTCTC N GTGAAT SEQ ID NO: 6961

GTTTCCCAGTAGGTCTC N GTGACA SEQ ID NO: 6962

GTTTCCCAGTAGGTCTC N GTGACT SEQ ID NO: 6963

GTTTCCCAGTAGGTCTC N GTGCAA SEQ ID NO: 6964

GTTTCCCAGTAGGTCTC N GTGCAT SEQ ID NO: 6965

GTTTCCCAGTAGGTCTC N GTGCTA SEQ ID NO: 6966

GTTTCCCAGTAGGTCTC N GTGGAA SEQ ID NO: 6967

GTTTCCCAGTAGGTCTC N GTGGAT SEQ ID NO: 6968

GTTTCCCAGTAGGTCTC N GTGTCG SEQ ID NO: 6969

GTTTCCCAGTAGGTCTC N GTGTCT SEQ ID NO: 6970

GTTTCCCAGTAGGTCTC N GTTAAC SEQ ID NO: 6971

GTTTCCCAGTAGGTCTC N GTTAAG SEQ ID NO: 6972

GTTTCCCAGTAGGTCTC N GTTAGA SEQ ID NO: 6973

GTTTCCCAGTAGGTCTC N GTTGCA SEQ ID NO: 6974

GTTTCCCAGTAGGTCTC N GTTGCC SEQ ID NO: 6975

GTTTCCCAGTAGGTCTC N GTTGCG SEQ ID NO: 6976

GTTTCCCAGTAGGTCTC N GTTGCT SEQ ID NO: 6977

GTTTCCCAGTAGGTCTC N GTTGGA SEQ ID NO: 6978

GTTTCCCAGTAGGTCTC N TAAAAT SEQ ID NO: 6979 G I N CCCAGTAGGTCTC N TAACAA SEQ ID NO: 6980

GTTTCCCAGTAGGTCTC N TAACCG SEQ ID NO: 6981

GTTTCCCAGTAGGTCTC N TAACGA SEQ ID NO: 6982

GTTTCCCAGTAGGTCTC N TAACTC SEQ ID NO: 6983

GTTTCCCAGTAGGTCTC N TAAGAC SEQ ID NO: 6984

GTTTCCCAGTAGGTCTC N TAAGGC SEQ ID NO: 6985

GTTTCCCAGTAGGTCTC N TAAGTA SEQ ID NO: 6986

GTTTCCCAGTAGGTCTC N TAATGC SEQ ID NO: 6987

GTTTCCCAGTAGGTCTC N TAATGG SEQ ID NO: 6988

GTTTCCCAGTAGGTCTC N TAATGT SEQ ID NO: 6989

GTTTCCCAGTAGGTCTC N TACAAT SEQ ID NO: 6990

GTTTCCCAGTAGGTCTC N TACACG SEQ ID NO: 6991

GTTTCCCAGTAGGTCTC N TACAGC SEQ ID NO: 6992

GTTTCCCAGTAGGTCTC N TACAGT SEQ ID NO: 6993

GTTTCCCAGTAGGTCTC N TACATC SEQ ID NO: 6994

GTTTCCCAGTAGGTCTC N TACATG SEQ ID NO: 6995

GTTTCCCAGTAGGTCTC N TACCAG SEQ ID NO: 6996

GTTTCCCAGTAGGTCTC N TACCCC SEQ ID NO: 6997

GTTTCCCAGTAGGTCTC N TACCCT SEQ ID NO: 6998

GTTTCCCAGTAGGTCTC N TACCGA SEQ ID NO: 6999

GTTTCCCAGTAGGTCTC N TACCTG SEQ ID NO: 7000

GTTTCCCAGTAGGTCTC N TACGAG SEQ ID NO: 7001

GTTTCCCAGTAGGTCTC N TACGAT SEQ ID NO: 7002

GTTTCCCAGTAGGTCTC N TACGCA SEQ ID NO: 7003

GTTTCCCAGTAGGTCTC N TACGCT SEQ ID NO: 7004

GTTTCCCAGTAGGTCTC N TACGTA SEQ ID NO: 7005

GTTTCCCAGTAGGTCTC N TACGTC SEQ ID NO: 7006

GTTTCCCAGTAGGTCTC N TACTCA SEQ ID NO: 7007

GTTTCCCAGTAGGTCTC N TACTGT SEQ ID NO: 7008

GTTTCCCAGTAGGTCTC N TACTTC SEQ ID NO: 7009

GTTTCCCAGTAGGTCTC N TAGAAG SEQ ID NO: 7010

GTTTCCCAGTAGGTCTC N TAGACA SEQ ID NO: 701 1

GTTTCCCAGTAGGTCTC N TAGACC SEQ ID NO: 7012

GTTTCCCAGTAGGTCTC N TAGACT SEQ ID NO: 7013

GTTTCCCAGTAGGTCTC N TAGAGA SEQ ID NO: 7014

GTTTCCCAGTAGGTCTC N TAGATC SEQ ID NO: 7015

GTTTCCCAGTAGGTCTC N TAGCAA SEQ ID NO: 7016

GTTTCCCAGTAGGTCTC N TAGCAC SEQ ID NO: 7017

GTTTCCCAGTAGGTCTC N TAGCAG SEQ ID NO: 7018

GTTTCCCAGTAGGTCTC N TAGCCA SEQ ID NO: 7019

GTTTCCCAGTAGGTCTC N TAGCGT SEQ ID NO: 7020

GTTTCCCAGTAGGTCTC N TAGGTC SEQ ID NO: 7021

GTTTCCCAGTAGGTCTC N TAGTAC SEQ ID NO: 7022 G I N CCCAGTAGGTCTC N TATAAC SEQ ID NO: 7023

GTTTCCCAGTAGGTCTC N TATACA SEQ ID NO: 7024

GTTTCCCAGTAGGTCTC N TATACG SEQ ID NO: 7025

GTTTCCCAGTAGGTCTC N TATAGT SEQ ID NO: 7026

GTTTCCCAGTAGGTCTC N TATCAC SEQ ID NO: 7027

GTTTCCCAGTAGGTCTC N TATCAG SEQ ID NO: 7028

GTTTCCCAGTAGGTCTC N TATCTC SEQ ID NO: 7029

GTTTCCCAGTAGGTCTC N TATGGA SEQ ID NO: 7030

GTTTCCCAGTAGGTCTC N TATGGC SEQ ID NO: 7031

GTTTCCCAGTAGGTCTC N TATGTA SEQ ID NO: 7032

GTTTCCCAGTAGGTCTC N TATGTC SEQ ID NO: 7033

GTTTCCCAGTAGGTCTC N TATTAC SEQ ID NO: 7034

GTTTCCCAGTAGGTCTC N TCAAGT SEQ ID NO: 7035

GTTTCCCAGTAGGTCTC N TCAATG SEQ ID NO: 7036

GTTTCCCAGTAGGTCTC N TCAGAC SEQ ID NO: 7037

GTTTCCCAGTAGGTCTC N TCAGCA SEQ ID NO: 7038

GTTTCCCAGTAGGTCTC N TCATAC SEQ ID NO: 7039

GTTTCCCAGTAGGTCTC N TCATCG SEQ ID NO: 7040

GTTTCCCAGTAGGTCTC N TCATGA SEQ ID NO: 7041

GTTTCCCAGTAGGTCTC N TCCACA SEQ ID NO: 7042

GTTTCCCAGTAGGTCTC N TCCAGA SEQ ID NO: 7043

GTTTCCCAGTAGGTCTC N TCCATA SEQ ID NO: 7044

GTTTCCCAGTAGGTCTC N TCCATC SEQ ID NO: 7045

GTTTCCCAGTAGGTCTC N TCCCAT SEQ ID NO: 7046

GTTTCCCAGTAGGTCTC N TCCGAT SEQ ID NO: 7047

GTTTCCCAGTAGGTCTC N TCCGTT SEQ ID NO: 7048

GTTTCCCAGTAGGTCTC N TCCTAC SEQ ID NO: 7049

GTTTCCCAGTAGGTCTC N TCCTTC SEQ ID NO: 7050

GTTTCCCAGTAGGTCTC N TCGACG SEQ ID NO: 7051

GTTTCCCAGTAGGTCTC N TCGAGC SEQ ID NO: 7052

GTTTCCCAGTAGGTCTC N TCGAGT SEQ ID NO: 7053

GTTTCCCAGTAGGTCTC N TCGATA SEQ ID NO: 7054

GTTTCCCAGTAGGTCTC N TCGATG SEQ ID NO: 7055

GTTTCCCAGTAGGTCTC N TCGCAA SEQ ID NO: 7056

GTTTCCCAGTAGGTCTC N TCGCAC SEQ ID NO: 7057

GTTTCCCAGTAGGTCTC N TCGCAG SEQ ID NO: 7058

GTTTCCCAGTAGGTCTC N TCGCCA SEQ ID NO: 7059

GTTTCCCAGTAGGTCTC N TCGGTG SEQ ID NO: 7060

GTTTCCCAGTAGGTCTC N TCGTAT SEQ ID NO: 7061

GTTTCCCAGTAGGTCTC N TCTAAC SEQ ID NO: 7062

GTTTCCCAGTAGGTCTC N TCTACC SEQ ID NO: 7063

GTTTCCCAGTAGGTCTC N TCTACG SEQ ID NO: 7064

GTTTCCCAGTAGGTCTC N TCTAGG SEQ ID NO: 7065 G I N CCCAGTAGGTCTC N TCTATG SEQ ID NO: 7066

GTTTCCCAGTAGGTCTC N TCTCAA SEQ ID NO: 7067

GTTTCCCAGTAGGTCTC N TCTCGC SEQ ID NO: 7068

GTTTCCCAGTAGGTCTC N TCTCTG SEQ ID NO: 7069

GTTTCCCAGTAGGTCTC N TCTGAG SEQ ID NO: 7070

GTTTCCCAGTAGGTCTC N TCTGCC SEQ ID NO: 7071

GTTTCCCAGTAGGTCTC N TCTGGA SEQ ID NO: 7072

GTTTCCCAGTAGGTCTC N TCTGTG SEQ ID NO: 7073

GTTTCCCAGTAGGTCTC N TCTGTT SEQ ID NO: 7074

GTTTCCCAGTAGGTCTC N TCTTAT SEQ ID NO: 7075

GTTTCCCAGTAGGTCTC N TGAAAC SEQ ID NO: 7076

GTTTCCCAGTAGGTCTC N TGAAAT SEQ ID NO: 7077

GTTTCCCAGTAGGTCTC N TGACAA SEQ ID NO: 7078

GTTTCCCAGTAGGTCTC N TGACGT SEQ ID NO: 7079

GTTTCCCAGTAGGTCTC N TGACTC SEQ ID NO: 7080

GTTTCCCAGTAGGTCTC N TGACTG SEQ ID NO: 7081

GTTTCCCAGTAGGTCTC N TGAGAC SEQ ID NO: 7082

GTTTCCCAGTAGGTCTC N TGATAC SEQ ID NO: 7083

GTTTCCCAGTAGGTCTC N TGCAAG SEQ ID NO: 7084

GTTTCCCAGTAGGTCTC N TGCACA SEQ ID NO: 7085

GTTTCCCAGTAGGTCTC N TGCAGG SEQ ID NO: 7086

GTTTCCCAGTAGGTCTC N TGCAGT SEQ ID NO: 7087

GTTTCCCAGTAGGTCTC N TGCATA SEQ ID NO: 7088

GTTTCCCAGTAGGTCTC N TGCATC SEQ ID NO: 7089

GTTTCCCAGTAGGTCTC N TGCCAA SEQ ID NO: 7090

GTTTCCCAGTAGGTCTC N TGCCAT SEQ ID NO: 7091

GTTTCCCAGTAGGTCTC N TGCCGC SEQ ID NO: 7092

GTTTCCCAGTAGGTCTC N TGCCTA SEQ ID NO: 7093

GTTTCCCAGTAGGTCTC N TGCGAA SEQ ID NO: 7094

GTTTCCCAGTAGGTCTC N TGCGAC SEQ ID NO: 7095

GTTTCCCAGTAGGTCTC N TGCGCA SEQ ID NO: 7096

GTTTCCCAGTAGGTCTC N TGCTGG SEQ ID NO: 7097

GTTTCCCAGTAGGTCTC N TGGAAA SEQ ID NO: 7098

GTTTCCCAGTAGGTCTC N TGGAAG SEQ ID NO: 7099

GTTTCCCAGTAGGTCTC N TGGAAT SEQ ID NO: 7100

GTTTCCCAGTAGGTCTC N TGGACA SEQ ID NO: 7101

GTTTCCCAGTAGGTCTC N TGGACC SEQ ID NO: 7102

GTTTCCCAGTAGGTCTC N TGGAGC SEQ ID NO: 7103

GTTTCCCAGTAGGTCTC N TGGCAG SEQ ID NO: 7104

GTTTCCCAGTAGGTCTC N TGGCAT SEQ ID NO: 7105

GTTTCCCAGTAGGTCTC N TGGCGC SEQ ID NO: 7106

GTTTCCCAGTAGGTCTC N TGGCGT SEQ ID NO: 7107

GTTTCCCAGTAGGTCTC N TGGGAC SEQ ID NO: 7108 G I N CCCAGTAGGTCTC N TGGGAG SEQ ID NO: 7109

GTTTCCCAGTAGGTCTC N TGGTAC SEQ ID NO: 71 10

GTTTCCCAGTAGGTCTC N TGGTAT SEQ ID NO: 71 1 1

GTTTCCCAGTAGGTCTC N TGGTCT SEQ ID NO: 71 12

GTTTCCCAGTAGGTCTC N TGTAAC SEQ ID NO: 71 13

GTTTCCCAGTAGGTCTC N TGTACT SEQ ID NO: 71 14

GTTTCCCAGTAGGTCTC N TGTAGT SEQ ID NO: 71 15

GTTTCCCAGTAGGTCTC N TGTATC SEQ ID NO: 71 16

GTTTCCCAGTAGGTCTC N TGTCAT SEQ ID NO: 71 17

GTTTCCCAGTAGGTCTC N TGTCGA SEQ ID NO: 71 18

GTTTCCCAGTAGGTCTC N TGTCGC SEQ ID NO: 71 19

GTTTCCCAGTAGGTCTC N TGTCGG SEQ ID NO: 7120

GTTTCCCAGTAGGTCTC N TGTCGT SEQ ID NO: 7121

GTTTCCCAGTAGGTCTC N TGTCTT SEQ ID NO: 7122

GTTTCCCAGTAGGTCTC N TGTGCA SEQ ID NO: 7123

GTTTCCCAGTAGGTCTC N TGTGCG SEQ ID NO: 7124

GTTTCCCAGTAGGTCTC N TGTGGA SEQ ID NO: 7125

GTTTCCCAGTAGGTCTC N TGTTCG SEQ ID NO: 7126

GTTTCCCAGTAGGTCTC N TGTTGC SEQ ID NO: 7127

GTTTCCCAGTAGGTCTC N TTAACA SEQ ID NO: 7128

GTTTCCCAGTAGGTCTC N TTACAT SEQ ID NO: 7129

GTTTCCCAGTAGGTCTC N TTAGAA SEQ ID NO: 7130

GTTTCCCAGTAGGTCTC N TTAGAC SEQ ID NO: 7131

GTTTCCCAGTAGGTCTC N TTATTA SEQ ID NO: 7132

GTTTCCCAGTAGGTCTC N TTCCGG SEQ ID NO: 7133

GTTTCCCAGTAGGTCTC N TTCCTG SEQ ID NO: 7134

GTTTCCCAGTAGGTCTC N TTCGAG SEQ ID NO: 7135

GTTTCCCAGTAGGTCTC N TTCGCA SEQ ID NO: 7136

GTTTCCCAGTAGGTCTC N TTCGTG SEQ ID NO: 7137

GTTTCCCAGTAGGTCTC N TTGAAA SEQ ID NO: 7138

GTTTCCCAGTAGGTCTC N TTGACG SEQ ID NO: 7139

GTTTCCCAGTAGGTCTC N TTGCAG SEQ ID NO: 7140

GTTTCCCAGTAGGTCTC N TTGCCT SEQ ID NO: 7141

GTTTCCCAGTAGGTCTC N TTGCGA SEQ ID NO: 7142

GTTTCCCAGTAGGTCTC N TTGCTT SEQ ID NO: 7143

GTTTCCCAGTAGGTCTC N TTGGAA SEQ ID NO: 7144

GTTTCCCAGTAGGTCTC N TTGTCG SEQ ID NO: 7145

GTTTCCCAGTAGGTCTC N TTGTGC SEQ ID NO: 7146

GTTTCCCAGTAGGTCTC N TTTCCG SEQ ID NO: 7147

GTTTCCCAGTAGGTCTC N TTTGTC SEQ ID NO: 7148

[00111] The reverse strand (RS-MEP) primer set used in this experiment is provided 9. TABLE 9

GTTTCCCAGTAGGTCTC N ACATTA SEQ ID NO: 7186

GTTTCCCAGTAGGTCTC N ACATTG SEQ ID NO: 7187

GTTTCCCAGTAGGTCTC N ACCACT SEQ ID NO: 7188

GTTTCCCAGTAGGTCTC N ACCAGC SEQ ID NO: 7189

GTTTCCCAGTAGGTCTC N ACCCTT SEQ ID NO: 7190

GTTTCCCAGTAGGTCTC N ACCGAG SEQ ID NO: 7191

GTTTCCCAGTAGGTCTC N ACCGCT SEQ ID NO: 7192

GTTTCCCAGTAGGTCTC N ACCGGG SEQ ID NO: 7193

GTTTCCCAGTAGGTCTC N ACCGGT SEQ ID NO: 7194

GTTTCCCAGTAGGTCTC N ACGAAG SEQ ID NO: 7195

GTTTCCCAGTAGGTCTC N ACGACA SEQ ID NO: 7196

GTTTCCCAGTAGGTCTC N ACGACG SEQ ID NO: 7197

GTTTCCCAGTAGGTCTC N AC G ACT SEQ ID NO: 7198

GTTTCCCAGTAGGTCTC N ACGCCA SEQ ID NO: 7199

GTTTCCCAGTAGGTCTC N ACGCGG SEQ ID NO: 7200

GTTTCCCAGTAGGTCTC N ACGCGT SEQ ID NO: 7201

GTTTCCCAGTAGGTCTC N ACGCTG SEQ ID NO: 7202

GTTTCCCAGTAGGTCTC N ACGGAG SEQ ID NO: 7203

GTTTCCCAGTAGGTCTC N ACGGAT SEQ ID NO: 7204

GTTTCCCAGTAGGTCTC N ACGGCA SEQ ID NO: 7205

GTTTCCCAGTAGGTCTC N ACGGTC SEQ ID NO: 7206

GTTTCCCAGTAGGTCTC N ACGGTT SEQ ID NO: 7207

GTTTCCCAGTAGGTCTC N ACGTAC SEQ ID NO: 7208

GTTTCCCAGTAGGTCTC N ACGTAG SEQ ID NO: 7209

GTTTCCCAGTAGGTCTC N ACGTAT SEQ ID NO: 7210

GTTTCCCAGTAGGTCTC N ACGTCA SEQ ID NO: 721 1

GTTTCCCAGTAGGTCTC N ACGTCC SEQ ID NO: 7212

GTTTCCCAGTAGGTCTC N ACGTTC SEQ ID NO: 7213

GTTTCCCAGTAGGTCTC N ACGTTG SEQ ID NO: 7214

GTTTCCCAGTAGGTCTC N ACGTTT SEQ ID NO: 7215

GTTTCCCAGTAGGTCTC N ACTACA SEQ ID NO: 7216

GTTTCCCAGTAGGTCTC N ACTCAG SEQ ID NO: 7217

GTTTCCCAGTAGGTCTC N ACTCCG SEQ ID NO: 7218

GTTTCCCAGTAGGTCTC N ACTCGA SEQ ID NO: 7219

GTTTCCCAGTAGGTCTC N ACTCGC SEQ ID NO: 7220

GTTTCCCAGTAGGTCTC N ACTCGG SEQ ID NO: 7221

GTTTCCCAGTAGGTCTC N ACTCGT SEQ ID NO: 7222

GTTTCCCAGTAGGTCTC N ACTGCA SEQ ID NO: 7223

GTTTCCCAGTAGGTCTC N ACTGTA SEQ ID NO: 7224 GTTTCCCAGTAGGTCTC N ACTTAC SEQ ID NO: 7225

GTTTCCCAGTAGGTCTC N ACTTGT SEQ ID NO: 7226

GTTTCCCAGTAGGTCTC N AGAAGT SEQ ID NO: 7227

GTTTCCCAGTAGGTCTC N AGACAC SEQ ID NO: 7228

GTTTCCCAGTAGGTCTC N AGACCA SEQ ID NO: 7229

GTTTCCCAGTAGGTCTC N AGACCT SEQ ID NO: 7230

GTTTCCCAGTAGGTCTC N AGACGC SEQ ID NO: 7231

GTTTCCCAGTAGGTCTC N AGACTG SEQ ID NO: 7232

GTTTCCCAGTAGGTCTC N AGACTT SEQ ID NO: 7233

GTTTCCCAGTAGGTCTC N AGAGCA SEQ ID NO: 7234

GTTTCCCAGTAGGTCTC N AGAGGC SEQ ID NO: 7235

GTTTCCCAGTAGGTCTC N AGATCG SEQ ID NO: 7236

GTTTCCCAGTAGGTCTC N AGATGC SEQ ID NO: 7237

GTTTCCCAGTAGGTCTC N AGATTT SEQ ID NO: 7238

GTTTCCCAGTAGGTCTC N AGCAAC SEQ ID NO: 7239

GTTTCCCAGTAGGTCTC N AGCACA SEQ ID NO: 7240

GTTTCCCAGTAGGTCTC N AGCACT SEQ ID NO: 7241

GTTTCCCAGTAGGTCTC N AGCATG SEQ ID NO: 7242

GTTTCCCAGTAGGTCTC N AGCCGT SEQ ID NO: 7243

GTTTCCCAGTAGGTCTC N AGCGAG SEQ ID NO: 7244

GTTTCCCAGTAGGTCTC N AGCGCT SEQ ID NO: 7245

GTTTCCCAGTAGGTCTC N AGCGTA SEQ ID NO: 7246

GTTTCCCAGTAGGTCTC N AGCTCC SEQ ID NO: 7247

GTTTCCCAGTAGGTCTC N AGCTGC SEQ ID NO: 7248

GTTTCCCAGTAGGTCTC N AGCTGT SEQ ID NO: 7249

GTTTCCCAGTAGGTCTC N AGGCAA SEQ ID NO: 7250

GTTTCCCAGTAGGTCTC N AGGCAC SEQ ID NO: 7251

GTTTCCCAGTAGGTCTC N AGGCTG SEQ ID NO: 7252

GTTTCCCAGTAGGTCTC N AGGGGG SEQ ID NO: 7253

GTTTCCCAGTAGGTCTC N AGGGGT SEQ ID NO: 7254

GTTTCCCAGTAGGTCTC N AGGGTA SEQ ID NO: 7255

GTTTCCCAGTAGGTCTC N AGGTAC SEQ ID NO: 7256

GTTTCCCAGTAGGTCTC N AGGTAT SEQ ID NO: 7257

GTTTCCCAGTAGGTCTC N AGGTTG SEQ ID NO: 7258

GTTTCCCAGTAGGTCTC N AGTACA SEQ ID NO: 7259

GTTTCCCAGTAGGTCTC N AGTAGT SEQ ID NO: 7260

GTTTCCCAGTAGGTCTC N AGTATT SEQ ID NO: 7261

GTTTCCCAGTAGGTCTC N AGTCAC SEQ ID NO: 7262

GTTTCCCAGTAGGTCTC N AGTCTA SEQ ID NO: 7263 GTTTCCCAGTAGGTCTC N AGTCTC SEQ ID NO: 7264

GTTTCCCAGTAGGTCTC N AGTGGT SEQ ID NO: 7265

GTTTCCCAGTAGGTCTC N AGTTAG SEQ ID NO: 7266

GTTTCCCAGTAGGTCTC N AGTTCG SEQ ID NO: 7267

GTTTCCCAGTAGGTCTC N ATAAGA SEQ ID NO: 7268

GTTTCCCAGTAGGTCTC N ATACCA SEQ ID NO: 7269

GTTTCCCAGTAGGTCTC N ATACGA SEQ ID NO: 7270

GTTTCCCAGTAGGTCTC N ATACGT SEQ ID NO: 7271

GTTTCCCAGTAGGTCTC N ATACTG SEQ ID NO: 7272

GTTTCCCAGTAGGTCTC N ATAGTG SEQ ID NO: 7273

GTTTCCCAGTAGGTCTC N ATAGTT SEQ ID NO: 7274

GTTTCCCAGTAGGTCTC N ATATCG SEQ ID NO: 7275

GTTTCCCAGTAGGTCTC N ATATGC SEQ ID NO: 7276

GTTTCCCAGTAGGTCTC N ATATGG SEQ ID NO: 7277

GTTTCCCAGTAGGTCTC N ATATGT SEQ ID NO: 7278

GTTTCCCAGTAGGTCTC N ATATTG SEQ ID NO: 7279

GTTTCCCAGTAGGTCTC N ATATTT SEQ ID NO: 7280

GTTTCCCAGTAGGTCTC N ATCAAT SEQ ID NO: 7281

GTTTCCCAGTAGGTCTC N ATCACG SEQ ID NO: 7282

GTTTCCCAGTAGGTCTC N ATCACT SEQ ID NO: 7283

GTTTCCCAGTAGGTCTC N ATCATG SEQ ID NO: 7284

GTTTCCCAGTAGGTCTC N ATCCAC SEQ ID NO: 7285

GTTTCCCAGTAGGTCTC N ATCGAC SEQ ID NO: 7286

GTTTCCCAGTAGGTCTC N ATCGCC SEQ ID NO: 7287

GTTTCCCAGTAGGTCTC N ATCGGA SEQ ID NO: 7288

GTTTCCCAGTAGGTCTC N ATCGGC SEQ ID NO: 7289

GTTTCCCAGTAGGTCTC N ATCGTA SEQ ID NO: 7290

GTTTCCCAGTAGGTCTC N ATCGTC SEQ ID NO: 7291

GTTTCCCAGTAGGTCTC N ATCGTG SEQ ID NO: 7292

GTTTCCCAGTAGGTCTC N ATCGTT SEQ ID NO: 7293

GTTTCCCAGTAGGTCTC N ATCTCC SEQ ID NO: 7294

GTTTCCCAGTAGGTCTC N ATCTGC SEQ ID NO: 7295

GTTTCCCAGTAGGTCTC N ATCTGG SEQ ID NO: 7296

GTTTCCCAGTAGGTCTC N ATCTTT SEQ ID NO: 7297

GTTTCCCAGTAGGTCTC N ATGACA SEQ ID NO: 7298

GTTTCCCAGTAGGTCTC N ATGACG SEQ ID NO: 7299

GTTTCCCAGTAGGTCTC N ATGAGT SEQ ID NO: 7300

GTTTCCCAGTAGGTCTC N ATGATC SEQ ID NO: 7301

GTTTCCCAGTAGGTCTC N ATGCAC SEQ ID NO: 7302 GTTTCCCAGTAGGTCTC N ATGCAT SEQ ID NO: 7303

GTTTCCCAGTAGGTCTC N ATGCCA SEQ ID NO: 7304

GTTTCCCAGTAGGTCTC N ATGCGC SEQ ID NO: 7305

GTTTCCCAGTAGGTCTC N ATGCTG SEQ ID NO: 7306

GTTTCCCAGTAGGTCTC N ATGGAC SEQ ID NO: 7307

GTTTCCCAGTAGGTCTC N ATGGAG SEQ ID NO: 7308

GTTTCCCAGTAGGTCTC N ATGGCA SEQ ID NO: 7309

GTTTCCCAGTAGGTCTC N ATGGGA SEQ ID NO: 7310

GTTTCCCAGTAGGTCTC N ATGGTC SEQ ID NO: 731 1

GTTTCCCAGTAGGTCTC N ATGTAA SEQ ID NO: 7312

GTTTCCCAGTAGGTCTC N ATGTAC SEQ ID NO: 7313

GTTTCCCAGTAGGTCTC N ATGTAT SEQ ID NO: 7314

GTTTCCCAGTAGGTCTC N ATGTCT SEQ ID NO: 7315

GTTTCCCAGTAGGTCTC N ATGTGG SEQ ID NO: 7316

GTTTCCCAGTAGGTCTC N ATTACG SEQ ID NO: 7317

GTTTCCCAGTAGGTCTC N ATTACT SEQ ID NO: 7318

GTTTCCCAGTAGGTCTC N ATTAGG SEQ ID NO: 7319

GTTTCCCAGTAGGTCTC N ATTCAC SEQ ID NO: 7320

GTTTCCCAGTAGGTCTC N ATTCCA SEQ ID NO: 7321

GTTTCCCAGTAGGTCTC N ATTCGG SEQ ID NO: 7322

GTTTCCCAGTAGGTCTC N ATTCTG SEQ ID NO: 7323

GTTTCCCAGTAGGTCTC N ATTGCT SEQ ID NO: 7324

GTTTCCCAGTAGGTCTC N ATTGGG SEQ ID NO: 7325

GTTTCCCAGTAGGTCTC N ATTGGT SEQ ID NO: 7326

GTTTCCCAGTAGGTCTC N ATTGTA SEQ ID NO: 7327

GTTTCCCAGTAGGTCTC N ATTGTC SEQ ID NO: 7328

GTTTCCCAGTAGGTCTC N ATTTCA SEQ ID NO: 7329

GTTTCCCAGTAGGTCTC N ATTTTA SEQ ID NO: 7330

GTTTCCCAGTAGGTCTC N CAACAT SEQ ID NO: 7331

GTTTCCCAGTAGGTCTC N CAACGT SEQ ID NO: 7332

GTTTCCCAGTAGGTCTC N CAACTG SEQ ID NO: 7333

GTTTCCCAGTAGGTCTC N CAAGGC SEQ ID NO: 7334

GTTTCCCAGTAGGTCTC N CAATAC SEQ ID NO: 7335

GTTTCCCAGTAGGTCTC N CAATCG SEQ ID NO: 7336

GTTTCCCAGTAGGTCTC N CAATTC SEQ ID NO: 7337

GTTTCCCAGTAGGTCTC N CACATT SEQ ID NO: 7338

GTTTCCCAGTAGGTCTC N CACCAT SEQ ID NO: 7339

GTTTCCCAGTAGGTCTC N CACCGA SEQ ID NO: 7340

GTTTCCCAGTAGGTCTC N CACCGT SEQ ID NO: 7341 GTTTCCCAGTAGGTCTC N CACGAA SEQ ID NO: 7342

GTTTCCCAGTAGGTCTC N CACGAC SEQ ID NO: 7343

GTTTCCCAGTAGGTCTC N CACGCT SEQ ID NO: 7344

GTTTCCCAGTAGGTCTC N CACGGC SEQ ID NO: 7345

GTTTCCCAGTAGGTCTC N CACGTC SEQ ID NO: 7346

GTTTCCCAGTAGGTCTC N CACGTT SEQ ID NO: 7347

GTTTCCCAGTAGGTCTC N CACTCG SEQ ID NO: 7348

GTTTCCCAGTAGGTCTC N CACTGG SEQ ID NO: 7349

GTTTCCCAGTAGGTCTC N CAGACT SEQ ID NO: 7350

GTTTCCCAGTAGGTCTC N CAGAGA SEQ ID NO: 7351

GTTTCCCAGTAGGTCTC N CAGAGT SEQ ID NO: 7352

GTTTCCCAGTAGGTCTC N CAGATG SEQ ID NO: 7353

GTTTCCCAGTAGGTCTC N CAGCAT SEQ ID NO: 7354

GTTTCCCAGTAGGTCTC N CAGCTG SEQ ID NO: 7355

GTTTCCCAGTAGGTCTC N CAGGAA SEQ ID NO: 7356

GTTTCCCAGTAGGTCTC N CAGGCT SEQ ID NO: 7357

GTTTCCCAGTAGGTCTC N CAGGTA SEQ ID NO: 7358

GTTTCCCAGTAGGTCTC N CAGTAG SEQ ID NO: 7359

GTTTCCCAGTAGGTCTC N CAGTAT SEQ ID NO: 7360

GTTTCCCAGTAGGTCTC N CAGTCA SEQ ID NO: 7361

GTTTCCCAGTAGGTCTC N CAGTCT SEQ ID NO: 7362

GTTTCCCAGTAGGTCTC N CAGTGG SEQ ID NO: 7363

GTTTCCCAGTAGGTCTC N CAGTGT SEQ ID NO: 7364

GTTTCCCAGTAGGTCTC N CATACG SEQ ID NO: 7365

GTTTCCCAGTAGGTCTC N CATAGA SEQ ID NO: 7366

GTTTCCCAGTAGGTCTC N CATATG SEQ ID NO: 7367

GTTTCCCAGTAGGTCTC N CATCCG SEQ ID NO: 7368

GTTTCCCAGTAGGTCTC N CATCGA SEQ ID NO: 7369

GTTTCCCAGTAGGTCTC N CATCGG SEQ ID NO: 7370

GTTTCCCAGTAGGTCTC N CATCGT SEQ ID NO: 7371

GTTTCCCAGTAGGTCTC N CATCTC SEQ ID NO: 7372

GTTTCCCAGTAGGTCTC N CATGCG SEQ ID NO: 7373

GTTTCCCAGTAGGTCTC N CATGTA SEQ ID NO: 7374

GTTTCCCAGTAGGTCTC N CATTAC SEQ ID NO: 7375

GTTTCCCAGTAGGTCTC N CATTAG SEQ ID NO: 7376

GTTTCCCAGTAGGTCTC N CATTGA SEQ ID NO: 7377

GTTTCCCAGTAGGTCTC N CATTGG SEQ ID NO: 7378

GTTTCCCAGTAGGTCTC N CATTTC SEQ ID NO: 7379

GTTTCCCAGTAGGTCTC N CCAGAT SEQ ID NO: 7380 GTTTCCCAGTAGGTCTC N CCAGCA SEQ ID NO: 7381

GTTTCCCAGTAGGTCTC N CCATGC SEQ ID NO: 7382

GTTTCCCAGTAGGTCTC N CCATTA SEQ ID NO: 7383

GTTTCCCAGTAGGTCTC N CCATTG SEQ ID NO: 7384

GTTTCCCAGTAGGTCTC N CCCGTA SEQ ID NO: 7385

GTTTCCCAGTAGGTCTC N CCGACA SEQ ID NO: 7386

GTTTCCCAGTAGGTCTC N CCGATT SEQ ID NO: 7387

GTTTCCCAGTAGGTCTC N CCGCGT SEQ ID NO: 7388

GTTTCCCAGTAGGTCTC N CCGCTT SEQ ID NO: 7389

GTTTCCCAGTAGGTCTC N CCGGAA SEQ ID NO: 7390

GTTTCCCAGTAGGTCTC N CCGGTT SEQ ID NO: 7391

GTTTCCCAGTAGGTCTC N CCGTAT SEQ ID NO: 7392

GTTTCCCAGTAGGTCTC N CCGTGT SEQ ID NO: 7393

GTTTCCCAGTAGGTCTC N CCGTTT SEQ ID NO: 7394

GTTTCCCAGTAGGTCTC N CCTAGA SEQ ID NO: 7395

GTTTCCCAGTAGGTCTC N CCTATG SEQ ID NO: 7396

GTTTCCCAGTAGGTCTC N CCTCAT SEQ ID NO: 7397

GTTTCCCAGTAGGTCTC N CCTGCA SEQ ID NO: 7398

GTTTCCCAGTAGGTCTC N CCTGGT SEQ ID NO: 7399

GTTTCCCAGTAGGTCTC N CCTGTG SEQ ID NO: 7400

GTTTCCCAGTAGGTCTC N CGAAAT SEQ ID NO: 7401

GTTTCCCAGTAGGTCTC N CGAACA SEQ ID NO: 7402

GTTTCCCAGTAGGTCTC N CGAATT SEQ ID NO: 7403

GTTTCCCAGTAGGTCTC N CGACAA SEQ ID NO: 7404

GTTTCCCAGTAGGTCTC N CGACAC SEQ ID NO: 7405

GTTTCCCAGTAGGTCTC N CGACAG SEQ ID NO: 7406

GTTTCCCAGTAGGTCTC N CGACAT SEQ ID NO: 7407

GTTTCCCAGTAGGTCTC N CGACTC SEQ ID NO: 7408

GTTTCCCAGTAGGTCTC N CGAGGA SEQ ID NO: 7409

GTTTCCCAGTAGGTCTC N CGAGTC SEQ ID NO: 7410

GTTTCCCAGTAGGTCTC N CGAGTT SEQ ID NO: 741 1

GTTTCCCAGTAGGTCTC N C GAT AT SEQ ID NO: 7412

GTTTCCCAGTAGGTCTC N CGATGA SEQ ID NO: 7413

GTTTCCCAGTAGGTCTC N CGATTG SEQ ID NO: 7414

GTTTCCCAGTAGGTCTC N CGCAAC SEQ ID NO: 7415

GTTTCCCAGTAGGTCTC N CGCACA SEQ ID NO: 7416

GTTTCCCAGTAGGTCTC N CGCATC SEQ ID NO: 7417

GTTTCCCAGTAGGTCTC N CGCGTC SEQ ID NO: 7418

GTTTCCCAGTAGGTCTC N CGCGTG SEQ ID NO: 7419 GTTTCCCAGTAGGTCTC N CGCGTT SEQ ID NO: 7420

GTTTCCCAGTAGGTCTC N CGCTGT SEQ ID NO: 7421

GTTTCCCAGTAGGTCTC N CGGAAA SEQ ID NO: 7422

GTTTCCCAGTAGGTCTC N CGGATA SEQ ID NO: 7423

GTTTCCCAGTAGGTCTC N CGGATG SEQ ID NO: 7424

GTTTCCCAGTAGGTCTC N CGGATT SEQ ID NO: 7425

GTTTCCCAGTAGGTCTC N CGGCAT SEQ ID NO: 7426

GTTTCCCAGTAGGTCTC N CGGCCT SEQ ID NO: 7427

GTTTCCCAGTAGGTCTC N CGGGAC SEQ ID NO: 7428

GTTTCCCAGTAGGTCTC N CGGGGT SEQ ID NO: 7429

GTTTCCCAGTAGGTCTC N CGGTAT SEQ ID NO: 7430

GTTTCCCAGTAGGTCTC N CGGTCT SEQ ID NO: 7431

GTTTCCCAGTAGGTCTC N CGGTTA SEQ ID NO: 7432

GTTTCCCAGTAGGTCTC N CGGTTG SEQ ID NO: 7433

GTTTCCCAGTAGGTCTC N CGTAAT SEQ ID NO: 7434

GTTTCCCAGTAGGTCTC N CGTACT SEQ ID NO: 7435

GTTTCCCAGTAGGTCTC N CGTAGA SEQ ID NO: 7436

GTTTCCCAGTAGGTCTC N CGTAGG SEQ ID NO: 7437

GTTTCCCAGTAGGTCTC N CGTATA SEQ ID NO: 7438

GTTTCCCAGTAGGTCTC N CGTATC SEQ ID NO: 7439

GTTTCCCAGTAGGTCTC N CGTATG SEQ ID NO: 7440

GTTTCCCAGTAGGTCTC N CGTCAA SEQ ID NO: 7441

GTTTCCCAGTAGGTCTC N CGTCCT SEQ ID NO: 7442

GTTTCCCAGTAGGTCTC N CGTCGA SEQ ID NO: 7443

GTTTCCCAGTAGGTCTC N CGTCTA SEQ ID NO: 7444

GTTTCCCAGTAGGTCTC N CGTCTT SEQ ID NO: 7445

GTTTCCCAGTAGGTCTC N CGTGAC SEQ ID NO: 7446

GTTTCCCAGTAGGTCTC N CGTGCG SEQ ID NO: 7447

GTTTCCCAGTAGGTCTC N CGTGCT SEQ ID NO: 7448

GTTTCCCAGTAGGTCTC N CGTGGT SEQ ID NO: 7449

GTTTCCCAGTAGGTCTC N CGTGTA SEQ ID NO: 7450

GTTTCCCAGTAGGTCTC N CGTGTC SEQ ID NO: 7451

GTTTCCCAGTAGGTCTC N CGTTAC SEQ ID NO: 7452

GTTTCCCAGTAGGTCTC N CGTTCG SEQ ID NO: 7453

GTTTCCCAGTAGGTCTC N CGTTGT SEQ ID NO: 7454

GTTTCCCAGTAGGTCTC N CGTTTC SEQ ID NO: 7455

GTTTCCCAGTAGGTCTC N CGTTTT SEQ ID NO: 7456

GTTTCCCAGTAGGTCTC N CTAACG SEQ ID NO: 7457

GTTTCCCAGTAGGTCTC N CTACAG SEQ ID NO: 7458 GTTTCCCAGTAGGTCTC N CTACGG SEQ ID NO: 7459

GTTTCCCAGTAGGTCTC N CTAGAC SEQ ID NO: 7460

GTTTCCCAGTAGGTCTC N CTAGCG SEQ ID NO: 7461

GTTTCCCAGTAGGTCTC N CTAGGT SEQ ID NO: 7462

GTTTCCCAGTAGGTCTC N CTATCG SEQ ID NO: 7463

GTTTCCCAGTAGGTCTC N CTATGT SEQ ID NO: 7464

GTTTCCCAGTAGGTCTC N CTCATG SEQ ID NO: 7465

GTTTCCCAGTAGGTCTC N CTCCCA SEQ ID NO: 7466

GTTTCCCAGTAGGTCTC N CTCGAA SEQ ID NO: 7467

GTTTCCCAGTAGGTCTC N CTCGAC SEQ ID NO: 7468

GTTTCCCAGTAGGTCTC N CTCGAG SEQ ID NO: 7469

GTTTCCCAGTAGGTCTC N CTCGGT SEQ ID NO: 7470

GTTTCCCAGTAGGTCTC N CTCGTT SEQ ID NO: 7471

GTTTCCCAGTAGGTCTC N CTCTAC SEQ ID NO: 7472

GTTTCCCAGTAGGTCTC N CTCTGC SEQ ID NO: 7473

GTTTCCCAGTAGGTCTC N CTCTGT SEQ ID NO: 7474

GTTTCCCAGTAGGTCTC N CTGATA SEQ ID NO: 7475

GTTTCCCAGTAGGTCTC N CTGATT SEQ ID NO: 7476

GTTTCCCAGTAGGTCTC N CTGCAA SEQ ID NO: 7477

GTTTCCCAGTAGGTCTC N CTGCCA SEQ ID NO: 7478

GTTTCCCAGTAGGTCTC N CTGCGC SEQ ID NO: 7479

GTTTCCCAGTAGGTCTC N CTGCTA SEQ ID NO: 7480

GTTTCCCAGTAGGTCTC N CTGCTG SEQ ID NO: 7481

GTTTCCCAGTAGGTCTC N CTGCTT SEQ ID NO: 7482

GTTTCCCAGTAGGTCTC N CTGGTA SEQ ID NO: 7483

GTTTCCCAGTAGGTCTC N CTGGTC SEQ ID NO: 7484

GTTTCCCAGTAGGTCTC N CTGTAG SEQ ID NO: 7485

GTTTCCCAGTAGGTCTC N CTGTAT SEQ ID NO: 7486

GTTTCCCAGTAGGTCTC N CTGTCG SEQ ID NO: 7487

GTTTCCCAGTAGGTCTC N CTGTCT SEQ ID NO: 7488

GTTTCCCAGTAGGTCTC N CTGTGC SEQ ID NO: 7489

GTTTCCCAGTAGGTCTC N CTGTGT SEQ ID NO: 7490

GTTTCCCAGTAGGTCTC N CTTAAC SEQ ID NO: 7491

GTTTCCCAGTAGGTCTC N CTTACG SEQ ID NO: 7492

GTTTCCCAGTAGGTCTC N CTTAGG SEQ ID NO: 7493

GTTTCCCAGTAGGTCTC N CTTATT SEQ ID NO: 7494

GTTTCCCAGTAGGTCTC N CTTCCA SEQ ID NO: 7495

GTTTCCCAGTAGGTCTC N CTTCGT SEQ ID NO: 7496

GTTTCCCAGTAGGTCTC N CTTCTA SEQ ID NO: 7497 GTTTCCCAGTAGGTCTC N CTTGAG SEQ ID NO: 7498

GTTTCCCAGTAGGTCTC N CTTGCA SEQ ID NO: 7499

GTTTCCCAGTAGGTCTC N CTTGTC SEQ ID NO: 7500

GTTTCCCAGTAGGTCTC N CTTGTT SEQ ID NO: 7501

GTTTCCCAGTAGGTCTC N CTTTAT SEQ ID NO: 7502

GTTTCCCAGTAGGTCTC N CTTTCC SEQ ID NO: 7503

GTTTCCCAGTAGGTCTC N GAAATC SEQ ID NO: 7504

GTTTCCCAGTAGGTCTC N GAAGAT SEQ ID NO: 7505

GTTTCCCAGTAGGTCTC N GAAGGA SEQ ID NO: 7506

GTTTCCCAGTAGGTCTC N GAAGTA SEQ ID NO: 7507

GTTTCCCAGTAGGTCTC N GAATAT SEQ ID NO: 7508

GTTTCCCAGTAGGTCTC N GAATCG SEQ ID NO: 7509

GTTTCCCAGTAGGTCTC N GACAAA SEQ ID NO: 7510

GTTTCCCAGTAGGTCTC N GACACC SEQ ID NO: 751 1

GTTTCCCAGTAGGTCTC N GACATA SEQ ID NO: 7512

GTTTCCCAGTAGGTCTC N GACCTA SEQ ID NO: 7513

GTTTCCCAGTAGGTCTC N GACGCC SEQ ID NO: 7514

GTTTCCCAGTAGGTCTC N GACGTA SEQ ID NO: 7515

GTTTCCCAGTAGGTCTC N GACTAT SEQ ID NO: 7516

GTTTCCCAGTAGGTCTC N GACTCG SEQ ID NO: 7517

GTTTCCCAGTAGGTCTC N GACTGC SEQ ID NO: 7518

GTTTCCCAGTAGGTCTC N GACTTC SEQ ID NO: 7519

GTTTCCCAGTAGGTCTC N GACTTG SEQ ID NO: 7520

GTTTCCCAGTAGGTCTC N GACTTT SEQ ID NO: 7521

GTTTCCCAGTAGGTCTC N GAGAAT SEQ ID NO: 7522

GTTTCCCAGTAGGTCTC N GAGACG SEQ ID NO: 7523

GTTTCCCAGTAGGTCTC N GAGATA SEQ ID NO: 7524

GTTTCCCAGTAGGTCTC N GAGATC SEQ ID NO: 7525

GTTTCCCAGTAGGTCTC N GAGCAT SEQ ID NO: 7526

GTTTCCCAGTAGGTCTC N GAGGAT SEQ ID NO: 7527

GTTTCCCAGTAGGTCTC N GAGGCA SEQ ID NO: 7528

GTTTCCCAGTAGGTCTC N GAGGCT SEQ ID NO: 7529

GTTTCCCAGTAGGTCTC N GAGTAC SEQ ID NO: 7530

GTTTCCCAGTAGGTCTC N GAGTCA SEQ ID NO: 7531

GTTTCCCAGTAGGTCTC N GAGTCT SEQ ID NO: 7532

GTTTCCCAGTAGGTCTC N GAGTTA SEQ ID NO: 7533

GTTTCCCAGTAGGTCTC N GATAAT SEQ ID NO: 7534

GTTTCCCAGTAGGTCTC N GATACA SEQ ID NO: 7535

GTTTCCCAGTAGGTCTC N GATACT SEQ ID NO: 7536 GTTTCCCAGTAGGTCTC N GATAGG SEQ ID NO: 7537

GTTTCCCAGTAGGTCTC N GATATC SEQ ID NO: 7538

GTTTCCCAGTAGGTCTC N GATATG SEQ ID NO: 7539

GTTTCCCAGTAGGTCTC N GATATT SEQ ID NO: 7540

GTTTCCCAGTAGGTCTC N GATCGT SEQ ID NO: 7541

GTTTCCCAGTAGGTCTC N GATCTA SEQ ID NO: 7542

GTTTCCCAGTAGGTCTC N GATGAC SEQ ID NO: 7543

GTTTCCCAGTAGGTCTC N GATGAG SEQ ID NO: 7544

GTTTCCCAGTAGGTCTC N GATGCA SEQ ID NO: 7545

GTTTCCCAGTAGGTCTC N GATGGA SEQ ID NO: 7546

GTTTCCCAGTAGGTCTC N GATGTA SEQ ID NO: 7547

GTTTCCCAGTAGGTCTC N GATTCA SEQ ID NO: 7548

GTTTCCCAGTAGGTCTC N GATTCG SEQ ID NO: 7549

GTTTCCCAGTAGGTCTC N GATTCT SEQ ID NO: 7550

GTTTCCCAGTAGGTCTC N GCAACA SEQ ID NO: 7551

GTTTCCCAGTAGGTCTC N GCAACC SEQ ID NO: 7552

GTTTCCCAGTAGGTCTC N GCAACG SEQ ID NO: 7553

GTTTCCCAGTAGGTCTC N GCAACT SEQ ID NO: 7554

GTTTCCCAGTAGGTCTC N GCACAA SEQ ID NO: 7555

GTTTCCCAGTAGGTCTC N GCACAC SEQ ID NO: 7556

GTTTCCCAGTAGGTCTC N GCACAT SEQ ID NO: 7557

GTTTCCCAGTAGGTCTC N GCACCG SEQ ID NO: 7558

GTTTCCCAGTAGGTCTC N GCACCT SEQ ID NO: 7559

GTTTCCCAGTAGGTCTC N GCACTC SEQ ID NO: 7560

GTTTCCCAGTAGGTCTC N GCACTG SEQ ID NO: 7561

GTTTCCCAGTAGGTCTC N GCAGAG SEQ ID NO: 7562

GTTTCCCAGTAGGTCTC N GCAGCG SEQ ID NO: 7563

GTTTCCCAGTAGGTCTC N GCATAG SEQ ID NO: 7564

GTTTCCCAGTAGGTCTC N GCATCT SEQ ID NO: 7565

GTTTCCCAGTAGGTCTC N GCATTA SEQ ID NO: 7566

GTTTCCCAGTAGGTCTC N GCATTG SEQ ID NO: 7567

GTTTCCCAGTAGGTCTC N GCCAGT SEQ ID NO: 7568

GTTTCCCAGTAGGTCTC N GCCATA SEQ ID NO: 7569

GTTTCCCAGTAGGTCTC N GCCATT SEQ ID NO: 7570

GTTTCCCAGTAGGTCTC N GCCTTA SEQ ID NO: 7571

GTTTCCCAGTAGGTCTC N GCGACA SEQ ID NO: 7572

GTTTCCCAGTAGGTCTC N GCGACT SEQ ID NO: 7573

GTTTCCCAGTAGGTCTC N GCGAGA SEQ ID NO: 7574

GTTTCCCAGTAGGTCTC N GCGATC SEQ ID NO: 7575 GTTTCCCAGTAGGTCTC N GCGCCA SEQ ID NO: 7576

GTTTCCCAGTAGGTCTC N GCGCTT SEQ ID NO: 7577

GTTTCCCAGTAGGTCTC N GCGGAT SEQ ID NO: 7578

GTTTCCCAGTAGGTCTC N GCGGCA SEQ ID NO: 7579

GTTTCCCAGTAGGTCTC N GCGTAG SEQ ID NO: 7580

GTTTCCCAGTAGGTCTC N GCGTAT SEQ ID NO: 7581

GTTTCCCAGTAGGTCTC N GCGTCT SEQ ID NO: 7582

GTTTCCCAGTAGGTCTC N GCTACT SEQ ID NO: 7583

GTTTCCCAGTAGGTCTC N GCTAGC SEQ ID NO: 7584

GTTTCCCAGTAGGTCTC N GCTAGT SEQ ID NO: 7585

GTTTCCCAGTAGGTCTC N GCTATC SEQ ID NO: 7586

GTTTCCCAGTAGGTCTC N GCTCCA SEQ ID NO: 7587

GTTTCCCAGTAGGTCTC N GCTCGA SEQ ID NO: 7588

GTTTCCCAGTAGGTCTC N GCTCGG SEQ ID NO: 7589

GTTTCCCAGTAGGTCTC N GCTGAT SEQ ID NO: 7590

GTTTCCCAGTAGGTCTC N GCTGCC SEQ ID NO: 7591

GTTTCCCAGTAGGTCTC N GCTGCT SEQ ID NO: 7592

GTTTCCCAGTAGGTCTC N GCTGTA SEQ ID NO: 7593

GTTTCCCAGTAGGTCTC N GCTGTC SEQ ID NO: 7594

GTTTCCCAGTAGGTCTC N GCTGTG SEQ ID NO: 7595

GTTTCCCAGTAGGTCTC N GCTGTT SEQ ID NO: 7596

GTTTCCCAGTAGGTCTC N GCTTAT SEQ ID NO: 7597

GTTTCCCAGTAGGTCTC N GCTTCG SEQ ID NO: 7598

GTTTCCCAGTAGGTCTC N GCTTCT SEQ ID NO: 7599

GTTTCCCAGTAGGTCTC N GGAAAT SEQ ID NO: 7600

GTTTCCCAGTAGGTCTC N GGAAGC SEQ ID NO: 7601

GTTTCCCAGTAGGTCTC N GGACGT SEQ ID NO: 7602

GTTTCCCAGTAGGTCTC N GGACTG SEQ ID NO: 7603

GTTTCCCAGTAGGTCTC N GGACTT SEQ ID NO: 7604

GTTTCCCAGTAGGTCTC N GGAGCT SEQ ID NO: 7605

GTTTCCCAGTAGGTCTC N GGAGGC SEQ ID NO: 7606

GTTTCCCAGTAGGTCTC N GGATAT SEQ ID NO: 7607

GTTTCCCAGTAGGTCTC N GGATGT SEQ ID NO: 7608

GTTTCCCAGTAGGTCTC N GGCAAC SEQ ID NO: 7609

GTTTCCCAGTAGGTCTC N GGCAAT SEQ ID NO: 7610

GTTTCCCAGTAGGTCTC N GGCACT SEQ ID NO: 761 1

GTTTCCCAGTAGGTCTC N GGCAGA SEQ ID NO: 7612

GTTTCCCAGTAGGTCTC N GGCATC SEQ ID NO: 7613

GTTTCCCAGTAGGTCTC N GGCCAG SEQ ID NO: 7614 GTTTCCCAGTAGGTCTC N GGCCTG SEQ ID NO: 7615

GTTTCCCAGTAGGTCTC N GGCCTT SEQ ID NO: 7616

GTTTCCCAGTAGGTCTC N GGCTAG SEQ ID NO: 7617

GTTTCCCAGTAGGTCTC N GGCTCC SEQ ID NO: 7618

GTTTCCCAGTAGGTCTC N GGCTGT SEQ ID NO: 7619

GTTTCCCAGTAGGTCTC N GGCTTC SEQ ID NO: 7620

GTTTCCCAGTAGGTCTC N GGGACC SEQ ID NO: 7621

GTTTCCCAGTAGGTCTC N GGGACT SEQ ID NO: 7622

GTTTCCCAGTAGGTCTC N GGGCTC SEQ ID NO: 7623

GTTTCCCAGTAGGTCTC N GGGGGT SEQ ID NO: 7624

GTTTCCCAGTAGGTCTC N GGGGTA SEQ ID NO: 7625

GTTTCCCAGTAGGTCTC N GGGGTG SEQ ID NO: 7626

GTTTCCCAGTAGGTCTC N GGGGTT SEQ ID NO: 7627

GTTTCCCAGTAGGTCTC N GGGTAC SEQ ID NO: 7628

GTTTCCCAGTAGGTCTC N GGGTAG SEQ ID NO: 7629

GTTTCCCAGTAGGTCTC N GGGTGC SEQ ID NO: 7630

GTTTCCCAGTAGGTCTC N GGTACC SEQ ID NO: 7631

GTTTCCCAGTAGGTCTC N GGTACG SEQ ID NO: 7632

GTTTCCCAGTAGGTCTC N GGTACT SEQ ID NO: 7633

GTTTCCCAGTAGGTCTC N GGTAGA SEQ ID NO: 7634

GTTTCCCAGTAGGTCTC N GGTAGG SEQ ID NO: 7635

GTTTCCCAGTAGGTCTC N GGTATC SEQ ID NO: 7636

GTTTCCCAGTAGGTCTC N GGTATG SEQ ID NO: 7637

GTTTCCCAGTAGGTCTC N GGTATT SEQ ID NO: 7638

GTTTCCCAGTAGGTCTC N GGTCCA SEQ ID NO: 7639

GTTTCCCAGTAGGTCTC N GGTCTA SEQ ID NO: 7640

GTTTCCCAGTAGGTCTC N GGTGAT SEQ ID NO: 7641

GTTTCCCAGTAGGTCTC N GGTGCC SEQ ID NO: 7642

GTTTCCCAGTAGGTCTC N GGTTAC SEQ ID NO: 7643

GTTTCCCAGTAGGTCTC N GGTTAT SEQ ID NO: 7644

GTTTCCCAGTAGGTCTC N GGTTGT SEQ ID NO: 7645

GTTTCCCAGTAGGTCTC N GTAATA SEQ ID NO: 7646

GTTTCCCAGTAGGTCTC N GTAATG SEQ ID NO: 7647

GTTTCCCAGTAGGTCTC N GTACAG SEQ ID NO: 7648

GTTTCCCAGTAGGTCTC N GTACAT SEQ ID NO: 7649

GTTTCCCAGTAGGTCTC N GTACCA SEQ ID NO: 7650

GTTTCCCAGTAGGTCTC N GTACCT SEQ ID NO: 7651

GTTTCCCAGTAGGTCTC N GTACGC SEQ ID NO: 7652

GTTTCCCAGTAGGTCTC N GTACGT SEQ ID NO: 7653 GTTTCCCAGTAGGTCTC N GTACTA SEQ ID NO: 7654

GTTTCCCAGTAGGTCTC N GTAGAC SEQ ID NO: 7655

GTTTCCCAGTAGGTCTC N GTAGAT SEQ ID NO: 7656

GTTTCCCAGTAGGTCTC N GTAGGG SEQ ID NO: 7657

GTTTCCCAGTAGGTCTC N GTAGTG SEQ ID NO: 7658

GTTTCCCAGTAGGTCTC N GTATAT SEQ ID NO: 7659

GTTTCCCAGTAGGTCTC N GTATCA SEQ ID NO: 7660

GTTTCCCAGTAGGTCTC N GTATCG SEQ ID NO: 7661

GTTTCCCAGTAGGTCTC N GTATCT SEQ ID NO: 7662

GTTTCCCAGTAGGTCTC N GTATGA SEQ ID NO: 7663

GTTTCCCAGTAGGTCTC N GTATGC SEQ ID NO: 7664

GTTTCCCAGTAGGTCTC N GTATTA SEQ ID NO: 7665

GTTTCCCAGTAGGTCTC N GTATTC SEQ ID NO: 7666

GTTTCCCAGTAGGTCTC N GTATTT SEQ ID NO: 7667

GTTTCCCAGTAGGTCTC N GTCACG SEQ ID NO: 7668

GTTTCCCAGTAGGTCTC N GTCACT SEQ ID NO: 7669

GTTTCCCAGTAGGTCTC N GTCAGG SEQ ID NO: 7670

GTTTCCCAGTAGGTCTC N GTCATG SEQ ID NO: 7671

GTTTCCCAGTAGGTCTC N GTCCAC SEQ ID NO: 7672

GTTTCCCAGTAGGTCTC N GTCCCA SEQ ID NO: 7673

GTTTCCCAGTAGGTCTC N GTCCTC SEQ ID NO: 7674

GTTTCCCAGTAGGTCTC N GTCGAC SEQ ID NO: 7675

GTTTCCCAGTAGGTCTC N GTCGAT SEQ ID NO: 7676

GTTTCCCAGTAGGTCTC N GTCGCA SEQ ID NO: 7677

GTTTCCCAGTAGGTCTC N GTCGTT SEQ ID NO: 7678

GTTTCCCAGTAGGTCTC N GTCTAA SEQ ID NO: 7679

GTTTCCCAGTAGGTCTC N GTCTAC SEQ ID NO: 7680

GTTTCCCAGTAGGTCTC N GTCTAG SEQ ID NO: 7681

GTTTCCCAGTAGGTCTC N GTCTAT SEQ ID NO: 7682

GTTTCCCAGTAGGTCTC N GTCTCA SEQ ID NO: 7683

GTTTCCCAGTAGGTCTC N GTCTCT SEQ ID NO: 7684

GTTTCCCAGTAGGTCTC N GTCTGA SEQ ID NO: 7685

GTTTCCCAGTAGGTCTC N GTCTTA SEQ ID NO: 7686

GTTTCCCAGTAGGTCTC N GTGAAT SEQ ID NO: 7687

GTTTCCCAGTAGGTCTC N GTGACA SEQ ID NO: 7688

GTTTCCCAGTAGGTCTC N GTGATA SEQ ID NO: 7689

GTTTCCCAGTAGGTCTC N GTGCCC SEQ ID NO: 7690

GTTTCCCAGTAGGTCTC N GTGCCG SEQ ID NO: 7691

GTTTCCCAGTAGGTCTC N GTGCGA SEQ ID NO: 7692 GTTTCCCAGTAGGTCTC N GTGCGC SEQ ID NO: 7693

GTTTCCCAGTAGGTCTC N GTGCGT SEQ ID NO: 7694

GTTTCCCAGTAGGTCTC N GTGCTA SEQ ID NO: 7695

GTTTCCCAGTAGGTCTC N GTGCTG SEQ ID NO: 7696

GTTTCCCAGTAGGTCTC N GTGGTC SEQ ID NO: 7697

GTTTCCCAGTAGGTCTC N GTGGTT SEQ ID NO: 7698

GTTTCCCAGTAGGTCTC N GTGTCG SEQ ID NO: 7699

GTTTCCCAGTAGGTCTC N GTGTCT SEQ ID NO: 7700

GTTTCCCAGTAGGTCTC N GTGTGG SEQ ID NO: 7701

GTTTCCCAGTAGGTCTC N GTTAAC SEQ ID NO: 7702

GTTTCCCAGTAGGTCTC N GTTACA SEQ ID NO: 7703

GTTTCCCAGTAGGTCTC N GTTACT SEQ ID NO: 7704

GTTTCCCAGTAGGTCTC N GTTAGA SEQ ID NO: 7705

GTTTCCCAGTAGGTCTC N GTTAGC SEQ ID NO: 7706

GTTTCCCAGTAGGTCTC N GTTATA SEQ ID NO: 7707

GTTTCCCAGTAGGTCTC N GTTATC SEQ ID NO: 7708

GTTTCCCAGTAGGTCTC N GTTCGG SEQ ID NO: 7709

GTTTCCCAGTAGGTCTC N GTTGCG SEQ ID NO: 7710

GTTTCCCAGTAGGTCTC N GTTGGC SEQ ID NO: 771 1

GTTTCCCAGTAGGTCTC N GTTGGG SEQ ID NO: 7712

GTTTCCCAGTAGGTCTC N GTTGTC SEQ ID NO: 7713

GTTTCCCAGTAGGTCTC N GTTGTG SEQ ID NO: 7714

GTTTCCCAGTAGGTCTC N GTTTAT SEQ ID NO: 7715

GTTTCCCAGTAGGTCTC N GTTTCA SEQ ID NO: 7716

GTTTCCCAGTAGGTCTC N GTTTCG SEQ ID NO: 7717

GTTTCCCAGTAGGTCTC N GTTTGC SEQ ID NO: 7718

GTTTCCCAGTAGGTCTC N GTTTTG SEQ ID NO: 7719

GTTTCCCAGTAGGTCTC N GTTTTT SEQ ID NO: 7720

GTTTCCCAGTAGGTCTC N TAAAAT SEQ ID NO: 7721

GTTTCCCAGTAGGTCTC N TAACCG SEQ ID NO: 7722

GTTTCCCAGTAGGTCTC N TAACGT SEQ ID NO: 7723

GTTTCCCAGTAGGTCTC N TAACTC SEQ ID NO: 7724

GTTTCCCAGTAGGTCTC N TAAGTT SEQ ID NO: 7725

GTTTCCCAGTAGGTCTC N TAATAA SEQ ID NO: 7726

GTTTCCCAGTAGGTCTC N TAATCT SEQ ID NO: 7727

GTTTCCCAGTAGGTCTC N TAATGC SEQ ID NO: 7728

GTTTCCCAGTAGGTCTC N TAATTG SEQ ID NO: 7729

GTTTCCCAGTAGGTCTC N TACAAG SEQ ID NO: 7730

GTTTCCCAGTAGGTCTC N TACACG SEQ ID NO: 7731 GTTTCCCAGTAGGTCTC N TACAGC SEQ ID NO: 7732

GTTTCCCAGTAGGTCTC N TACAGG SEQ ID NO: 7733

GTTTCCCAGTAGGTCTC N TACAGT SEQ ID NO: 7734

GTTTCCCAGTAGGTCTC N TACATA SEQ ID NO: 7735

GTTTCCCAGTAGGTCTC N TACATC SEQ ID NO: 7736

GTTTCCCAGTAGGTCTC N TACCAA SEQ ID NO: 7737

GTTTCCCAGTAGGTCTC N TACCGA SEQ ID NO: 7738

GTTTCCCAGTAGGTCTC N TACCTG SEQ ID NO: 7739

GTTTCCCAGTAGGTCTC N TACGCT SEQ ID NO: 7740

GTTTCCCAGTAGGTCTC N TACGGC SEQ ID NO: 7741

GTTTCCCAGTAGGTCTC N TACGGG SEQ ID NO: 7742

GTTTCCCAGTAGGTCTC N TACGGT SEQ ID NO: 7743

GTTTCCCAGTAGGTCTC N TACGTA SEQ ID NO: 7744

GTTTCCCAGTAGGTCTC N TACGTC SEQ ID NO: 7745

GTTTCCCAGTAGGTCTC N TACGTT SEQ ID NO: 7746

GTTTCCCAGTAGGTCTC N TACTCG SEQ ID NO: 7747

GTTTCCCAGTAGGTCTC N TACTGC SEQ ID NO: 7748

GTTTCCCAGTAGGTCTC N TACTGT SEQ ID NO: 7749

GTTTCCCAGTAGGTCTC N TACTTA SEQ ID NO: 7750

GTTTCCCAGTAGGTCTC N TAGACG SEQ ID NO: 7751

GTTTCCCAGTAGGTCTC N TAGATT SEQ ID NO: 7752

GTTTCCCAGTAGGTCTC N TAGCAC SEQ ID NO: 7753

GTTTCCCAGTAGGTCTC N TAGCCG SEQ ID NO: 7754

GTTTCCCAGTAGGTCTC N TAGCGC SEQ ID NO: 7755

GTTTCCCAGTAGGTCTC N TAGCGT SEQ ID NO: 7756

GTTTCCCAGTAGGTCTC N TAGGCA SEQ ID NO: 7757

GTTTCCCAGTAGGTCTC N TAGGTG SEQ ID NO: 7758

GTTTCCCAGTAGGTCTC N TAGTGC SEQ ID NO: 7759

GTTTCCCAGTAGGTCTC N TAGTGT SEQ ID NO: 7760

GTTTCCCAGTAGGTCTC N TATACG SEQ ID NO: 7761

GTTTCCCAGTAGGTCTC N TATATC SEQ ID NO: 7762

GTTTCCCAGTAGGTCTC N TATATG SEQ ID NO: 7763

GTTTCCCAGTAGGTCTC N TATCGA SEQ ID NO: 7764

GTTTCCCAGTAGGTCTC N TATCGC SEQ ID NO: 7765

GTTTCCCAGTAGGTCTC N TATCGG SEQ ID NO: 7766

GTTTCCCAGTAGGTCTC N TATCGT SEQ ID NO: 7767

GTTTCCCAGTAGGTCTC N TATCTT SEQ ID NO: 7768

GTTTCCCAGTAGGTCTC N TATGAT SEQ ID NO: 7769

GTTTCCCAGTAGGTCTC N TATGCA SEQ ID NO: 7770 GTTTCCCAGTAGGTCTC N TATGCG SEQ ID NO: 7771

GTTTCCCAGTAGGTCTC N TATGGA SEQ ID NO: 7772

GTTTCCCAGTAGGTCTC N TATGGC SEQ ID NO: 7773

GTTTCCCAGTAGGTCTC N TATGGG SEQ ID NO: 7774

GTTTCCCAGTAGGTCTC N TATGTA SEQ ID NO: 7775

GTTTCCCAGTAGGTCTC N TATGTC SEQ ID NO: 7776

GTTTCCCAGTAGGTCTC N TATGTT SEQ ID NO: 7777

GTTTCCCAGTAGGTCTC N TATTCG SEQ ID NO: 7778

GTTTCCCAGTAGGTCTC N TATTGG SEQ ID NO: 7779

GTTTCCCAGTAGGTCTC N TATTGT SEQ ID NO: 7780

GTTTCCCAGTAGGTCTC N TATTTG SEQ ID NO: 7781

GTTTCCCAGTAGGTCTC N TCACAG SEQ ID NO: 7782

GTTTCCCAGTAGGTCTC N TCACCG SEQ ID NO: 7783

GTTTCCCAGTAGGTCTC N TCACGC SEQ ID NO: 7784

GTTTCCCAGTAGGTCTC N TCACGG SEQ ID NO: 7785

GTTTCCCAGTAGGTCTC N TCACGT SEQ ID NO: 7786

GTTTCCCAGTAGGTCTC N TCACTT SEQ ID NO: 7787

GTTTCCCAGTAGGTCTC N TCAGAG SEQ ID NO: 7788

GTTTCCCAGTAGGTCTC N TCAGGC SEQ ID NO: 7789

GTTTCCCAGTAGGTCTC N TCAGGT SEQ ID NO: 7790

GTTTCCCAGTAGGTCTC N TCAGTG SEQ ID NO: 7791

GTTTCCCAGTAGGTCTC N TCATGA SEQ ID NO: 7792

GTTTCCCAGTAGGTCTC N TCATGC SEQ ID NO: 7793

GTTTCCCAGTAGGTCTC N TCATGG SEQ ID NO: 7794

GTTTCCCAGTAGGTCTC N TCATGT SEQ ID NO: 7795

GTTTCCCAGTAGGTCTC N TCCAAC SEQ ID NO: 7796

GTTTCCCAGTAGGTCTC N TCCACA SEQ ID NO: 7797

GTTTCCCAGTAGGTCTC N TCCACG SEQ ID NO: 7798

GTTTCCCAGTAGGTCTC N TCCAGA SEQ ID NO: 7799

GTTTCCCAGTAGGTCTC N TCCATT SEQ ID NO: 7800

GTTTCCCAGTAGGTCTC N TCCCAG SEQ ID NO: 7801

GTTTCCCAGTAGGTCTC N TCCCTT SEQ ID NO: 7802

GTTTCCCAGTAGGTCTC N TCCGAG SEQ ID NO: 7803

GTTTCCCAGTAGGTCTC N TCCGTC SEQ ID NO: 7804

GTTTCCCAGTAGGTCTC N TCCTGG SEQ ID NO: 7805

GTTTCCCAGTAGGTCTC N TCCTGT SEQ ID NO: 7806

GTTTCCCAGTAGGTCTC N TCCTTG SEQ ID NO: 7807

GTTTCCCAGTAGGTCTC N TCGAAT SEQ ID NO: 7808

GTTTCCCAGTAGGTCTC N TCGACA SEQ ID NO: 7809 GTTTCCCAGTAGGTCTC N TCGACC SEQ ID NO: 7810

GTTTCCCAGTAGGTCTC N TCGACG SEQ ID NO: 781 1

GTTTCCCAGTAGGTCTC N TCGACT SEQ ID NO: 7812

GTTTCCCAGTAGGTCTC N TCGAGC SEQ ID NO: 7813

GTTTCCCAGTAGGTCTC N TCGAGT SEQ ID NO: 7814

GTTTCCCAGTAGGTCTC N TCGATC SEQ ID NO: 7815

GTTTCCCAGTAGGTCTC N TCGCAA SEQ ID NO: 7816

GTTTCCCAGTAGGTCTC N TCGCAT SEQ ID NO: 7817

GTTTCCCAGTAGGTCTC N TCGCGT SEQ ID NO: 7818

GTTTCCCAGTAGGTCTC N TCGGAT SEQ ID NO: 7819

GTTTCCCAGTAGGTCTC N TCGGTA SEQ ID NO: 7820

GTTTCCCAGTAGGTCTC N TCGGTG SEQ ID NO: 7821

GTTTCCCAGTAGGTCTC N TCGTAC SEQ ID NO: 7822

GTTTCCCAGTAGGTCTC N TCGTCG SEQ ID NO: 7823

GTTTCCCAGTAGGTCTC N TCGTCT SEQ ID NO: 7824

GTTTCCCAGTAGGTCTC N TCGTGT SEQ ID NO: 7825

GTTTCCCAGTAGGTCTC N TCGTTA SEQ ID NO: 7826

GTTTCCCAGTAGGTCTC N TCGTTC SEQ ID NO: 7827

GTTTCCCAGTAGGTCTC N TCGTTG SEQ ID NO: 7828

GTTTCCCAGTAGGTCTC N TCTAAC SEQ ID NO: 7829

GTTTCCCAGTAGGTCTC N TCTACG SEQ ID NO: 7830

GTTTCCCAGTAGGTCTC N TCTAGC SEQ ID NO: 7831

GTTTCCCAGTAGGTCTC N TCTAGG SEQ ID NO: 7832

GTTTCCCAGTAGGTCTC N TCTATG SEQ ID NO: 7833

GTTTCCCAGTAGGTCTC N TCTCAG SEQ ID NO: 7834

GTTTCCCAGTAGGTCTC N TCTCCC SEQ ID NO: 7835

GTTTCCCAGTAGGTCTC N TCTCGT SEQ ID NO: 7836

GTTTCCCAGTAGGTCTC N TCTCTA SEQ ID NO: 7837

GTTTCCCAGTAGGTCTC N TCTCTG SEQ ID NO: 7838

GTTTCCCAGTAGGTCTC N TCTGCG SEQ ID NO: 7839

GTTTCCCAGTAGGTCTC N TCTGCT SEQ ID NO: 7840

GTTTCCCAGTAGGTCTC N TCTGGA SEQ ID NO: 7841

GTTTCCCAGTAGGTCTC N TCTGGG SEQ ID NO: 7842

GTTTCCCAGTAGGTCTC N TCTGTC SEQ ID NO: 7843

GTTTCCCAGTAGGTCTC N TCTTCG SEQ ID NO: 7844

GTTTCCCAGTAGGTCTC N TCTTGT SEQ ID NO: 7845

GTTTCCCAGTAGGTCTC N TGAAGT SEQ ID NO: 7846

GTTTCCCAGTAGGTCTC N TGAATC SEQ ID NO: 7847

GTTTCCCAGTAGGTCTC N TGACAT SEQ ID NO: 7848 GTTTCCCAGTAGGTCTC N TGACCG SEQ ID NO: 7849

GTTTCCCAGTAGGTCTC N TGACGA SEQ ID NO: 7850

GTTTCCCAGTAGGTCTC N TGACTT SEQ ID NO: 7851

GTTTCCCAGTAGGTCTC N TGAGAT SEQ ID NO: 7852

GTTTCCCAGTAGGTCTC N TGAGGG SEQ ID NO: 7853

GTTTCCCAGTAGGTCTC N TGAGTA SEQ ID NO: 7854

GTTTCCCAGTAGGTCTC N TGAGTC SEQ ID NO: 7855

GTTTCCCAGTAGGTCTC N TGATAC SEQ ID NO: 7856

GTTTCCCAGTAGGTCTC N TGATTC SEQ ID NO: 7857

GTTTCCCAGTAGGTCTC N TGATTG SEQ ID NO: 7858

GTTTCCCAGTAGGTCTC N TGCAAC SEQ ID NO: 7859

GTTTCCCAGTAGGTCTC N TGCACA SEQ ID NO: 7860

GTTTCCCAGTAGGTCTC N TGCACC SEQ ID NO: 7861

GTTTCCCAGTAGGTCTC N TGCAGG SEQ ID NO: 7862

GTTTCCCAGTAGGTCTC N TGCATC SEQ ID NO: 7863

GTTTCCCAGTAGGTCTC N TGCCCG SEQ ID NO: 7864

GTTTCCCAGTAGGTCTC N TGCCGG SEQ ID NO: 7865

GTTTCCCAGTAGGTCTC N TGCCGT SEQ ID NO: 7866

GTTTCCCAGTAGGTCTC N TGCGAC SEQ ID NO: 7867

GTTTCCCAGTAGGTCTC N TGCGAT SEQ ID NO: 7868

GTTTCCCAGTAGGTCTC N TGCGCA SEQ ID NO: 7869

GTTTCCCAGTAGGTCTC N TGCGCG SEQ ID NO: 7870

GTTTCCCAGTAGGTCTC N TGCGCT SEQ ID NO: 7871

GTTTCCCAGTAGGTCTC N TGCGTA SEQ ID NO: 7872

GTTTCCCAGTAGGTCTC N TGCTAC SEQ ID NO: 7873

GTTTCCCAGTAGGTCTC N TGCTAG SEQ ID NO: 7874

GTTTCCCAGTAGGTCTC N TGCTAT SEQ ID NO: 7875

GTTTCCCAGTAGGTCTC N TGCTCC SEQ ID NO: 7876

GTTTCCCAGTAGGTCTC N TGCTGA SEQ ID NO: 7877

GTTTCCCAGTAGGTCTC N TGCTGG SEQ ID NO: 7878

GTTTCCCAGTAGGTCTC N TGCTGT SEQ ID NO: 7879

GTTTCCCAGTAGGTCTC N TGCTTT SEQ ID NO: 7880

GTTTCCCAGTAGGTCTC N TGGACT SEQ ID NO: 7881

GTTTCCCAGTAGGTCTC N TGGAGT SEQ ID NO: 7882

GTTTCCCAGTAGGTCTC N TGGCAG SEQ ID NO: 7883

GTTTCCCAGTAGGTCTC N TGGCTA SEQ ID NO: 7884

GTTTCCCAGTAGGTCTC N TGGGAC SEQ ID NO: 7885

GTTTCCCAGTAGGTCTC N TGGTAC SEQ ID NO: 7886

GTTTCCCAGTAGGTCTC N TGGTCT SEQ ID NO: 7887 GTTTCCCAGTAGGTCTC N TGTAAG SEQ ID NO: 7888

GTTTCCCAGTAGGTCTC N TGTACC SEQ ID NO: 7889

GTTTCCCAGTAGGTCTC N TGTAGT SEQ ID NO: 7890

GTTTCCCAGTAGGTCTC N TGTATA SEQ ID NO: 7891

GTTTCCCAGTAGGTCTC N TGTATC SEQ ID NO: 7892

GTTTCCCAGTAGGTCTC N TGTATT SEQ ID NO: 7893

GTTTCCCAGTAGGTCTC N TGTCAC SEQ ID NO: 7894

GTTTCCCAGTAGGTCTC N TGTCAT SEQ ID NO: 7895

GTTTCCCAGTAGGTCTC N TGTCGC SEQ ID NO: 7896

GTTTCCCAGTAGGTCTC N TGTCGT SEQ ID NO: 7897

GTTTCCCAGTAGGTCTC N TGTCTA SEQ ID NO: 7898

GTTTCCCAGTAGGTCTC N TGTCTC SEQ ID NO: 7899

GTTTCCCAGTAGGTCTC N TGTCTT SEQ ID NO: 7900

GTTTCCCAGTAGGTCTC N TGTGAC SEQ ID NO: 7901

GTTTCCCAGTAGGTCTC N TGTGCA SEQ ID NO: 7902

GTTTCCCAGTAGGTCTC N TGTGCG SEQ ID NO: 7903

GTTTCCCAGTAGGTCTC N TGTGGA SEQ ID NO: 7904

GTTTCCCAGTAGGTCTC N TGTGTC SEQ ID NO: 7905

GTTTCCCAGTAGGTCTC N TGTGTG SEQ ID NO: 7906

GTTTCCCAGTAGGTCTC N TGTTAA SEQ ID NO: 7907

GTTTCCCAGTAGGTCTC N TGTTAC SEQ ID NO: 7908

GTTTCCCAGTAGGTCTC N TGTTAT SEQ ID NO: 7909

GTTTCCCAGTAGGTCTC N TGTTCC SEQ ID NO: 7910

GTTTCCCAGTAGGTCTC N TGTTTC SEQ ID NO: 791 1

GTTTCCCAGTAGGTCTC N TGTTTG SEQ ID NO: 7912

GTTTCCCAGTAGGTCTC N TTAACG SEQ ID NO: 7913

GTTTCCCAGTAGGTCTC N TTAATG SEQ ID NO: 7914

GTTTCCCAGTAGGTCTC N TTACAG SEQ ID NO: 7915

GTTTCCCAGTAGGTCTC N TTACAT SEQ ID NO: 7916

GTTTCCCAGTAGGTCTC N TTACCG SEQ ID NO: 7917

GTTTCCCAGTAGGTCTC N TTACCT SEQ ID NO: 7918

GTTTCCCAGTAGGTCTC N TTACGT SEQ ID NO: 7919

GTTTCCCAGTAGGTCTC N TTACTC SEQ ID NO: 7920

GTTTCCCAGTAGGTCTC N TTACTG SEQ ID NO: 7921

GTTTCCCAGTAGGTCTC N TTAGCG SEQ ID NO: 7922

GTTTCCCAGTAGGTCTC N TTAGGC SEQ ID NO: 7923

GTTTCCCAGTAGGTCTC N TTAGGG SEQ ID NO: 7924

GTTTCCCAGTAGGTCTC N TTATCG SEQ ID NO: 7925

GTTTCCCAGTAGGTCTC N TTATCT SEQ ID NO: 7926 GTTTCCCAGTAGGTCTC N TTATGC SEQ ID NO: 7927

GTTTCCCAGTAGGTCTC N TTATGT SEQ ID NO: 7928

GTTTCCCAGTAGGTCTC N TTATTT SEQ ID NO: 7929

GTTTCCCAGTAGGTCTC N TTCACG SEQ ID NO: 7930

GTTTCCCAGTAGGTCTC N TTCACT SEQ ID NO: 7931

GTTTCCCAGTAGGTCTC N TTCAGG SEQ ID NO: 7932

GTTTCCCAGTAGGTCTC N TTCATC SEQ ID NO: 7933

GTTTCCCAGTAGGTCTC N TTCATG SEQ ID NO: 7934

GTTTCCCAGTAGGTCTC N TTCCAA SEQ ID NO: 7935

GTTTCCCAGTAGGTCTC N TTCCAC SEQ ID NO: 7936

GTTTCCCAGTAGGTCTC N TTCCTG SEQ ID NO: 7937

GTTTCCCAGTAGGTCTC N TTCGAC SEQ ID NO: 7938

GTTTCCCAGTAGGTCTC N TTCGAG SEQ ID NO: 7939

GTTTCCCAGTAGGTCTC N TTCGCA SEQ ID NO: 7940

GTTTCCCAGTAGGTCTC N TTCGGC SEQ ID NO: 7941

GTTTCCCAGTAGGTCTC N TTCGGT SEQ ID NO: 7942

GTTTCCCAGTAGGTCTC N TTCGTC SEQ ID NO: 7943

GTTTCCCAGTAGGTCTC N TTCTAA SEQ ID NO: 7944

GTTTCCCAGTAGGTCTC N TTCTGG SEQ ID NO: 7945

GTTTCCCAGTAGGTCTC N TTGAAT SEQ ID NO: 7946

GTTTCCCAGTAGGTCTC N TTGAGA SEQ ID NO: 7947

GTTTCCCAGTAGGTCTC N TTGAGT SEQ ID NO: 7948

GTTTCCCAGTAGGTCTC N TTGATG SEQ ID NO: 7949

GTTTCCCAGTAGGTCTC N TTGCAC SEQ ID NO: 7950

GTTTCCCAGTAGGTCTC N TTGCAG SEQ ID NO: 7951

GTTTCCCAGTAGGTCTC N TTGCAT SEQ ID NO: 7952

GTTTCCCAGTAGGTCTC N TTGCGA SEQ ID NO: 7953

GTTTCCCAGTAGGTCTC N TTGCGG SEQ ID NO: 7954

GTTTCCCAGTAGGTCTC N TTGCTA SEQ ID NO: 7955

GTTTCCCAGTAGGTCTC N TTGGAG SEQ ID NO: 7956

GTTTCCCAGTAGGTCTC N TTGGCA SEQ ID NO: 7957

GTTTCCCAGTAGGTCTC N TTGGCC SEQ ID NO: 7958

GTTTCCCAGTAGGTCTC N TTGGGC SEQ ID NO: 7959

GTTTCCCAGTAGGTCTC N TTGTAT SEQ ID NO: 7960

GTTTCCCAGTAGGTCTC N TTGTCA SEQ ID NO: 7961

GTTTCCCAGTAGGTCTC N TTGTCC SEQ ID NO: 7962

GTTTCCCAGTAGGTCTC N TTGTCG SEQ ID NO: 7963

GTTTCCCAGTAGGTCTC N TTGTGC SEQ ID NO: 7964

GTTTCCCAGTAGGTCTC N TTGTGT SEQ ID NO: 7965 GTTTCCCAGTAGGTCTC N TTGTTA SEQ ID NO: 7966

GTTTCCCAGTAGGTCTC N TTGTTT SEQ ID NO: 7967

GTTTCCCAGTAGGTCTC N TTTAGG SEQ ID NO: 7968

GTTTCCCAGTAGGTCTC N TTTAGT SEQ ID NO: 7969

GTTTCCCAGTAGGTCTC N TTTATG SEQ ID NO: 7970

GTTTCCCAGTAGGTCTC N TTTCAA SEQ ID NO: 7971

GTTTCCCAGTAGGTCTC N TTTCCA SEQ ID NO: 7972

GTTTCCCAGTAGGTCTC N TTTCCG SEQ ID NO: 7973

GTTTCCCAGTAGGTCTC N TTTCCT SEQ ID NO: 7974

GTTTCCCAGTAGGTCTC N TTTGAG SEQ ID NO: 7975

GTTTCCCAGTAGGTCTC N TTTGCG SEQ ID NO: 7976

GTTTCCCAGTAGGTCTC N TTTGCT SEQ ID NO: 7977

GTTTCCCAGTAGGTCTC N TTTGGC SEQ ID NO: 7978

GTTTCCCAGTAGGTCTC N TTTTCC SEQ ID NO: 7979

GTTTCCCAGTAGGTCTC N TTTTGC SEQ ID NO: 7980

GTTTCCCAGTAGGTCTC N TTTTTC SEQ ID NO: 7981

GTTTCCCAGTAGGTCTC N JTTTTT SEQ ID NO: 7982

Generation of a Library of MEP Primers

[00112] Total RNA (0.5 μg) from tissue samples was treated with DNAse I (Ambion DNA-free, Austin, TX, USA) and reverse transcribed by using superscript III (Invitrogen, Carlsbad, CA, USA) with the FS-MEP (forward strand microbe enrichment primers), as illustrated in Fig. 8. The reverse transcription reaction was incubated at 30 min at 40°C followed by an inactivation step of 75 °C for 15 min. Second-strand cDNA synthesis was carried out using RS-MEP (reverse strand microbe enrichment primers) and the 3' to 5' exo^" Klenow fragment (New England BioLabs, Ipswich, MA). The purified doubled stranded cDNA is amplified using the Extend primers (Fig. 3C). The resulting purified PCR product represents the library. PCR products are ligated to linkers for sequencing on a GSL FLX Sequencer (454 Life Sciences, Branford, CT, USA).

[00113] Sequence data generated over the course of 45 UHTS experiments performed with the 454-Roche sequencing platform was analyzed. For each library, sequence reads identified for human, 18S and 28S rRNA; mitochondrial 12S and 16S rRNA, ATP Synthase, NADH dehydrogenase (ND2, ND4, ND6) are selected and mapped to the reference sequences. The read distribution for each host gene is determined by coverage depth. The coverage depth for a given nucleotide in a reference sequence is evaluated as the number of reads that align to the reference sequence and cover this given nucleotide (Figs. 2A-2B).

[00114] The plot of the coverage depth as a function of the nucleotide position gives a quantitative measure of the read distribution and unravels the regions that are amplified (Fig. 4B). Figs. 6A-6D illustrate the normalized coverage depth for human genes 12S, 16S, 18S and 28S rR A for all 45 UHTS experiments. Regions giving a large number of reads (arbitrary cutoff: >1% of relative coverage depth) are identified. The coverage depth pattern slightly fluctuates between the different UHTS experiments and is tissue independent.

Identical analyses were conducted for mitochondrial host genes.

[00115] The analysis revealed a non-uniform coverage depth of host genes

(ribosomal (18S rRNA, 28S rRNA) and mitochondrial (12S rRNA, 16S rRNA, ATP

Synthase, NADH dehydrogenase) despite the fact that random primers were used to generate the cDNA libraries (2-3) (Figs. 6A-6D and 7A-7D). When this non-uniformity was investigated, a strong correlation was found between the presence of RNA secondary structures (e.g., rich G-C content) in RNAs and the absence of amplification of such region.

[00116] It was postulated that regions having strong secondary structures will impede cDNA synthesis. Prediction of secondary structures in a gene allows (at least qualitatively) to predict the distribution of reads throughout the gene (5). Thus, only primers with a similar sequence to the target gene and not present in a region comprising a secondary structure are able to generate sequence reads. All possible hexamer sequences with perfect sequence matches to the host regions giving >1% of relative coverage depth were excluded from the primer library (Figs. 6A-6D, Table 1). Focusing on these specific host regions allows to exclude only a minimal number of primers from the random hexamer library, thus increasing the sensitivity of microbial RNA detection.

[00117] The resultant microbe enrichment primer set (MEP), is composed of 828 hexamers for the forward strand MEP primers (FS-MEP) and 834 hexamers for the reverse strand MEP primers (RS-MEP).

Microbe Enrichment Primer (MEP) Synthesis

[00118] Each microbe enrichment primer was synthesized individually by Euro fins MWG Operon (Huntsville, AL, USA). Oligonucleotides were desalted and resuspended in water to 100 μΜ before pooling at equimolar concentrations. [00119] Table 10 shows Real Time PCR results on 18S and 28S ribosomal RNA genes of a liver specimen using the using random octamer primers (standard protocol) or MEP primers (MEP protocol).

TABLE 10

As can be seen from Table 10, the MEP protocol reduced the number of unwanted reads from the 18S rRNA gene approximately 7,000-fold, while the number of unwanted reads from the 28S rRNA gene was reduced approximately 200-fold.

[00120] To evaluate the performance of the MEP primers (MEP method), sequences obtained from cDNA libraries prepared with random primers (Standard Method) were compared with sequences obtained from cDNA library prepared with MEP primers from a liver sample infected with Lujo virus (6). After isolation of the total RNA from the sample, total RNA (250 to 500 ng) was reverse-transcribed using the Superscript III first strand synthesis reverse transcriptase (Invitrogen, Carlsbad, CA) and the FS-MEP primers. Second strand cDNA synthesis was performed using the Exo^" Klenow fragment (New England BioLabs, Ipswich, MA) and the reverse-strand MEP (RS-MEP) primers. Purified double stranded cDNAs are amplified using Expand plus enzyme and Extend primers (Roche Diagnostics, Branchburg, NJ).

[00121] Comparison of rRNA and viral sequences between both cDNA libraries revealed a 67 % depletion of host rRNA and a dramatic increase of the number of viral reads using the protocol with MEP primers, as seen in Table 11.

TABLE 11

[00122] Figs. 9A-9B show the raw coverage depth of Lujo virus for its S and L segments, respectively, using the MEP primers and using random primers. [00123] The results show that MEP primers provide efficient enrichment in microbial sequences. The methods described can be used to improve the design of primers and probes for use in microbial diagnostics. MEP primer sets can be used to generate libraries efficiently enriched for the presence of bacterial, viral, fungal, or other parasite sequences.

[00124] Experimental methods:

[00125] Step 1: A first strand of cDNA was prepared. Mix 1 was prepared by mixing R A template, water, and primers according to Table 12 below, and heating for 5 minutes at 65 °C.

Table 12: Mix 1

[00126] Mix 2 was prepared according to Table 13 below. Mix 1 was then added to Mix 2 and the combination was heated for 30 minutes at 40°C, then for 15 minutes at 75°C.

Table 13: Mix 2

[00127] Step 2: RNAse H (Invitrogen, Carlsbad, CA) was then added to the combination of Mix 1 and Mix 2, which was then heated for 20 minutes at 37°C, and then heated for 5 minutes at 70 °C.

[00128] Step 3: The combination of Mix 1 and Mix 2 was purified using the QIAquick™ purification kit (Qiagen, Valencia, CA), and eluted in 30 of water. This yielded a purified first strand of cDNA.

[00129] Step 4: The purified first strand of cDNA of Step 3 was mixed with the components listed in Table 14 below, then heated for 30 minutes at 37 °C. This yielded double-stranded cDNA. Table 14: Second strand cDNA synthesis

[00130] Step 5: The double-stranded cDNA from Step 4 was purified using the QIAquick™ purification kit (Qiagen, Valencia, CA), and eluted in 30 of water. This yielded purified double-stranded cDNA.

[00131] Step 6: The purified double-stranded cDNA from Step 5 was prepared as described in Table 4. PCR was performed according to Table 15.

Table 15: Purified double-stranded cDNA

[00132] Step 7: After the PCR reaction was completed, the resulting material was purified using the QIAquick™ purification kit (Qiagen, Valencia, CA), and eluted in 30 μΙ_, of water.

References

All of the references below are incorporated herein by reference in their entirety for the specific purpose they are mentioned in the text.

1. Armour et al., Digital transcriptome profiling using selective hexamer priming for cDNA synthesis, Nature Methods 6, 647-649 (2009).

2. Cox-Foster et al., 2007. A metagenomic survey of microbes in honey bee colony collapse disorder. Science 318:283-7.

3. Palacios et al., 2008. A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med 358:991-8.

4. Margulies et al., 2005. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437:376-80.

5. Hofacker et. al, Fast Folding and Comparison of R A Secondary Structures, Monatsh. Chem. 125, 167-188 (1994).

6. Briese et al., 2009. Genetic detection and characterization of Lujo virus, a new hemorrhagic fever associated arenavirus from southern Africa. PLoS Pathog 5:el000455.

Claims

Claims:

1. A composition comprising 20 or more nucleic acid sequences, wherein each of the 20 nucleic acid sequence comprises a different hexamer sequence selected from the group consisting of the hexamers sequences of any of SEQ ID NOs: 1-1662, provided that at least one nucleic sequence does not comprise a hexamer sequence selected from the group consisting of the hexamer sequences of any of SEQ ID NOs: 3325- 4822.

2. The composition of claim 1, wherein each different hexamer sequence is selected from the group consisting of the hexamer sequences of any of SEQ ID NOs: 1663- 2490.

3. The composition of claim 1, wherein each different hexamer sequence is selected from the group consisting of hexamer sequences of any of SEQ ID NOs: 2491-3324.

4. The composition of any one of claims 1-3 comprising 200 or more nucleic acid

sequences.

5. The composition of any one of claims 1-3 comprising 800 or more nucleic acid

sequences.

6. The composition of any one of claims 1-5, wherein each nucleic acid further

comprises a tail sequence 5 ' to the hexamer sequence, wherein the tail sequence is about 10 to about 22 nucleotides in length, wherein tail sequence is separated from the hexamer sequence by 0 to 10 nucleotides, wherein each nucleic acid comprises the same tail sequence.

7. The composition of any one of claims 1-6, wherein each nucleic acid sequence has the same length or substantially the same length.

8. The composition of any one of claims 1-7, wherein each nucleic acid has the hexamer sequence in the same position in the nucleic acid.

9. The composition of any one of claims 1-8, wherein each nucleic acid sequence is a primer.

10. The composition of any one of claims 1-9, wherein each nucleic sequence is DNA, RNA, PNA, LNA, GNA or TNA.

11. A method for designing a primer set for amplification of microbial nucleic acids in an organism comprising:

(a) sequencing the transcriptome of an organism;

(b) identifying highly expressed genes of the organism from the plurality of sequence reads identified in step (a);

(c) providing a first primer library, wherein each primer comprises a different hexamer sequence; and

(d) removing primers from the first primer library that are predicted to anneal to the RNA of the organism's highly expressed genes to generate a second primer library, provided that primers expected to anneal to the RNA predicted to form a secondary structure are not removed from the first primer library.

12. The method of claim 11, wherein primers comprising hexamer sequences with perfect sequence matches to the regions giving a substantial number of reads are removed from the first primer library.

13. The method of claim 12, wherein the substantial amount of reads is more than 1% of the relative coverage depth.

14. The method of any one of claims 11-13, wherein steps (b) or (d) are performed by a computer.

15. The method of any one of claims 11-14, wherein the organism's highly expressed genes comprise 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase, NADH dehydrogenase.

16. The method of claim 15, wherein the organism's highly expressed genes further

comprise one or more additional oxidative phosphorylation genes.

17. The method of any one of claims 11-16, wherein the transcriptome of the organisms is sequenced using unbiased high throughput sequencing.

- Ill -

18. The method of any one of claims 11-17, wherein the second primer library comprises 20 or more primers.

19. The method of any one of claims 11-18, wherein the second primer library comprises 800 or more primers.

20. The method of any one of claims 11-19, wherein the second primer library comprises 1600 or more primers.

21. The method of any one of claims 11-20, further comprising separating the primers in the second primer library into two primer sets.

22. The method of claim 21, wherein one primer set is used to generate a first cDNA strand from total R A and the other primer set is used to generate a second cDNA strand from the first cDNA strand.

23. The method of any one of claims 11-22, wherein the organism is a eukaryote.

24. The method of claim 23, wherein the organism is a human.

25. The method of any one of claims 11-24, further comprising producing the second primer library.

26. A method for amplifying a microbial nucleic acid comprising:

(a) providing a sample from an organism;

(b) isolating total RNA from the sample;

(c) reverse-transcribing total RNA from the sample using a set of forward strand primers to provide a first cDNA strand, wherein the forward strand primers are designed not to amplify organism's 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase and NADH dehydrogenase RNA transcripts, wherein the forward strand primers comprise primers complementary to regions predicted to form secondary RNA structure of the organism's 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase and NADH dehydrogenase RNA transcripts;

(d) replicating the first cDNA strand using a set of reverse strand primers to provide a second cDNA strand, wherein the reverse strand primers comprise primers are designed not to amplify organism's 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase and NADH dehydrogenase RNA transcripts, wherein the reverse strand primers comprise primers complementary to regions predicted to form secondary RNA structure of the organism's 18S rRNA, 28S rRNA, 12S rRNA, 16S rRNA, ATP synthase and NADH dehydrogenase RNA transcripts;

(e) allowing the first and the second cDNA strands to anneal to provide double- stranded cDNA; and

(f) amplifying the double stranded cDNA using polymerase chain reaction using double-strand cDNA primers.

27. The method of claim 26, wherein the forward strand primers and the reverse strand primers are further designed not to amplify the RNA transcripts of one or more additional oxidative phosphorylation genes.

28. The method of any one of claims 26-27, wherein the forward strand primers and the reverse strand primers each comprise a different hexamer sequence.

29. The method of any one of claims 26-28, wherein the forward strand primers and the reverse strand primers each comprise the same specific tail sequence.

30. The method of any one of claims 26-29, wherein at least one of the double-strand cDNA primers is complementary to the specific tail sequence or a portion thereof.

31. The method of any one of claims 26-30, wherein each forward strand primer

comprises a hexamer sequence selected from the group consisting of the hexamer sequences of any of SEQ ID NOs: 1663-2490.

32. The method of any one of claims 26-30, wherein each reverse strand primer

comprises a hexamer sequence selected from the group consisting of the hexamer sequences of any of SEQ ID NOs: 2491-3324.

33. The method of any one of claims 26-32, further comprising determining whether the organism is infected with a microbe.

34. A composition comprising 800 or more nucleic acids, wherein each nucleic acid has the structure: H-N_a-ST wherein H is a nucleotide sequence of 5 to 7 nucleotides; N is a random nucleotide; a is an integer from 0 to 12; and ST is a nucleotide sequence from 10-22 nucleotides, provided that each nucleic acid in the composition has a different sequence H.

35. The composition of claim 34, wherein H is a nucleotide sequence of 6 nucleotides.

36. The composition of any one of claims 34-35, wherein in at least one nucleic acid sequence H is not selected from the group consisting of the hexamer sequences of any of SEQ ID NOs: 3325-4822.

37. The composition of any one of claims 34-36, wherein H is selected from the group consisting of the hexamer sequences of any of SEQ ID NOs: 1663-2490.

38. The composition of any one of claims 34-36, wherein H is selected from the group consisting of the hexamer sequences of any of SEQ ID NOs: 2491-3324.

39. The composition of any one of claims 34-38, wherein a is 1.

40. The composition of any one of claims 34-39, comprising at least 1600 nucleic acids.

41. The composition of any one of claims 34-40, wherein ST is a nucleotide sequence of 17 nucleotides.

42. A kit comprising a composition of any one of claims 1-10 and 34-41 and instructions for use.