US20080032408A1 - Tag Nucleic Acids and Probe Arrays - Google Patents

Tag Nucleic Acids and Probe Arrays Download PDF

Info

Publication number
US20080032408A1
US20080032408A1 US11/562,548 US56254806A US2008032408A1 US 20080032408 A1 US20080032408 A1 US 20080032408A1 US 56254806 A US56254806 A US 56254806A US 2008032408 A1 US2008032408 A1 US 2008032408A1
Authority
US
United States
Prior art keywords
tag
nucleic acid
sequences
sequence
nos
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/562,548
Inventor
Michael Mittmann
Macdonald Morris
Thomas B. Ryder
David Lockhart
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Affymetrix Inc
Original Assignee
Affymetrix Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Affymetrix Inc filed Critical Affymetrix Inc
Priority to US11/562,548 priority Critical patent/US20080032408A1/en
Publication of US20080032408A1 publication Critical patent/US20080032408A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6834Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C12Q1/6837Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/13Tracers or tags

Definitions

  • This invention provides sets of nucleic acid tags, arrays of oligonucleotide probes, nucleic acid-tagged sets of recombinant cells and other compositions.
  • the invention relates to the selection and interaction of nucleic acids, and nucleic acids immobilized to solid substrates, including related chemistry, biology, and medical diagnostic uses.
  • FIG. 3 shows the array features from an array designed to probe for the tag sequences of the presently claimed invention. For each of the four tag-probes shown, arranged horizontally across the array, the brightest hybridization signal is seen with the “PM” feature.
  • FIG. 4 is a scanned image of the hybridization patterns resulting from the hybridization of 2050 different probes containing regions complementary to the SEQ ID Nos 1-2050 to an array comprised of tag-probes corresponding to SEQ ID Nos 1-2050.
  • FIG. 5 is a scanned image of the hybridization patterns resulting from the hybridization of 50 different probes containing regions complementary to SEQ ID Nos 2001-2050 to an array identical to the array depicted in FIG. 4 .
  • FIG. 6 shows signal intensities from two different independent experiments in which 2000 biotinylated oligonucleotide tags or 50 fluorescein labeled control oligonucleotides were hybridized to arrays designed as described above.
  • FIG. 7 shows the PM/MM ratios from the data described in FIG. 4 above.
  • an array may include a plurality of arrays unless the context clearly dictates otherwise.
  • array represents an intentionally created collection of molecules which can be prepared either synthetically or biosynthetically.
  • array herein means an intentionally created collection of polynucleotides attached to at least a first surface of at least one solid support wherein the identity of each polynucleotide at a given predefined region is known.
  • array biological chip
  • chips are used interchangeably.
  • At least one surface of the solid support will be substantially flat, although in some embodiments it may be desirable to physically separate synthesis regions for different compounds with, for example, wells, raised regions, pins, etched trenches, or the like.
  • the solid support(s) will take the form of beads, resins, gels, microspheres, fibers or other geometric configurations.
  • a “discrete, known location” refers to a localized area on a solid support which is, was, or is intended to be used for placement or fabrication of a selected molecule and is otherwise referred to herein in the alternative as a “selected” region.
  • the discrete, known location may have any convenient shape, e.g., circular, rectangular, elliptical, wedge-shaped, etc.
  • “discrete, known locations” are sometimes referred to as “predefined regions,” “regions,” or “features.”
  • a discrete, known location and, therefore, the area upon which each distinct compound is synthesized is smaller than about 1 cm or even less than 1 mm 2 .
  • a discrete, known location can be achieved by physically separating the regions (i.e., beads, fibers, resins, gels, etc.) into wells, trays, etc.
  • a “polynucleotide” is a sequence of two or more nucleotides.
  • Polynucleotides of the present invention include sequences of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) which may be isolated from natural sources, recombinantly produced, or artificially synthesized.
  • a further example of a polynucleotide of the present invention may be polyamide polynucleotide or peptide nucleic acid (PNA).
  • PNA peptide nucleic acid
  • This invention also encompasses situations in which there is nontraditional base pairing such as Hoogsteen base pairing which has been identified in certain tRNA molecules and postulated to exist in a triple helix.
  • “Polynucleotide” is used interchangeably with “oligonucleotide” is this application.
  • nucleotide and nucleic acid base include deoxynucleotides and analogs thereof. These analogs are those molecules having some structural features in common with a naturally occurring nucleotide such that when incorporated into a polynucleotide sequence, they allow hybridization with a complementary polynucleotide in solution. Typically, these analogs may have one or more modified bases, as well as modified forms of ribose and phosphodiester moieties. The changes can be tailor made to stabilize or destabilize hybrid formation, enhance the specificity of hybridization with a complementary polynucleotide sequence as desired, or enhance stability of the polynucleotide.
  • nucleic acid refers to a deoxyribonucleotide or ribonucleotide polymer in either single-or double-stranded form, and unless otherwise limited, would encompass analogs of natural nucleotides that can function in a similar manner as naturally occurring nucleotides.
  • Nucleic acids may be derived from a variety or sources including, but not limited to, naturally occurring nucleic acids, clones, synthesis in solution or solid phase synthesis.
  • a “probe” is defined as a nucleic acid capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation.
  • a probe may include natural (i.e. A, G, U, C, or T) or modified bases (7-deazaguanosine, inosine, etc.).
  • the bases in probes may be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization.
  • probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.
  • target nucleic acid refers to a nucleic acid or nucleic acid sequence which is to be analyzed.
  • a target can be a nucleic acid to which a probe will hybridize.
  • the probe may or may not be specifically designed to hybridize to the target. It is either the presence or absence of the target nucleic acid that is to be detected, or the amount of the target nucleic acid that is to be quantified.
  • target nucleic acid may refer to the specific subsequence of a larger nucleic acid to which the probe is directed or to the overall sequence (e.g., gene or mRNA) whose expression level it is desired to detect. The difference in usage will be apparent from context.
  • hybridization refers to the process in which two single-stranded polynucleotides bind non-covalently to form a stable double-stranded polynucleotide; triple-stranded hybridization is also theoretically possible.
  • the resulting (usually) double-stranded polynucleotide is a “hybrid.”
  • the proportion of the population of polynucleotides that forms stable hybrids is referred to herein as the “degree of hybridization.”
  • Hybrids can contain two DNA strands, two RNA strands, or one DNA and one RNA strand.
  • Hybridization assay procedures and conditions will vary depending on the application and are selected in accordance with the general binding methods known including those referred to in: Molecular Cloning, A Laboratory Manual, Second Ed., J. Sambrook et al., Eds., Cold Spring Harbor Laboratory Press, 1989 (“Sambrook et al.”); Berger and Kimmel, “Methods in Enzymology,” Vol. 152, “Guide to Molecular Cloning Techniques”, Academic Press, Inc., San Diego, Calif., 1987; Young and Davis, Proc. Natl. Acad. Sci., U.S.A., 80:1194 (1983), each of which are incorporated herein by reference.
  • stringency refers to the conditions of a hybridization reaction that influence the degree to which polynucleotides hybridize. Stringent conditions can be selected that allow polynucleotide duplexes to be distinguished based on their degree of mismatch. High stringency is correlated with a lower probability for the formation of a duplex containing mismatched bases. Thus, the higher the stringency, the greater the probability that two single-stranded polynucleotides, capable of forming a mismatched duplex, will remain single-stranded. Conversely, at lower stringency, the probability of formation of a mismatched duplex is increased.
  • a nucleic acid “tag” is a selected nucleic acid with a specified nucleic acid sequence.
  • a nucleic acid “probe” hybridizes to a nucleic acid “tag.”
  • a nucleic acid “tag-probe” is a specific sequence capable of hybridizing to a specific “tag.” Typically, the “tag-probe” is the complement or a partial complement of the “tag.” In one typical configuration, nucleic acid tags are incorporated as labels into biological libraries, and the tag nucleic acids are detected using a microarray.
  • the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range.
  • the description of a range such as 4 to 50 should be considered to have specifically disclosed all integers within the sub-ranges such as 4 to 10, 4 to 20, 4 to 30, 4 to 40, 4 to 50, 5 to 10, 5 to 20 etc., as well as individual numbers within that range, for example, 6, 8, 15, 20, 32, 39, 43, 48 etc. This applies regardless of the breadth of the range.
  • a description of a range such as 1 or more, 10 or more, 10 3 or more, 10 6 or more, or 10 12 or more should be considered to have specifically disclosed individual numbers within that range as well as higher numbers, for example, 20, 2 ⁇ 10 4 , 3 ⁇ 10 8 , 4 ⁇ 10 15 , 5 ⁇ 10 18 , etc.
  • the presently claimed invention provides 2050 unique sequences which have been specifically chosen according to strict criteria to produce sequences suitable for a wide variety of “tagging” applications. These sequences are provided as SEQ ID NOs 1-2050.
  • SEQ ID Nos 1-2050 comprise tag sequences. In a further embodiment, some or all of SEQ ID Nos 1-2050 comprise tag-probe sequences. In a further embodiment, the tag-probe sequences are immobilized to a solid support.
  • sequences of the presently claimed invention are tag-probes attached to a solid support.
  • Methods of immobilizing presynthesized sequences and synthesizing sequences de novo on solid supports are known. See for example, U.S. Pat.
  • SEQ ID Nos. 1-2000 may comprise the tag-probes and SEQ ID Nos. 2001-2050 may comprise the control probes.
  • the control probes are representative of the population with respect to observed signal intensities and discrimination.
  • tag sequences with relatively low signals may be over-represented in the control sequences so as to increase information about the sensitivity of experiments at the lower limit of detection.
  • tags may be used as a method of or as labels for a wide variety of biological and nonbiological materials, see, for example, Dollinger, The Polymerase Chain Reaction pp. 265-274 Mullis et al., editors (Birkhauser, Boston, 1994) or as a method of screening complex chemical libraries. See, for example, Brenner and Lerner, PNAS 89, 5281-5383 (1992); Alper, Science, 264: 1399-1401 (1994); and Needels et al. PNAS 90, 10700-10704 (1993). See also U.S. Pat. Nos. 4,359,353, 4,441,943, 5,451,505, 5,149,625, 5,654,413 and 5,800,992.
  • tag arrays may be used to identify the function of identified open reading frames (ORFs) by creating deletion mutants for each ORF and analyzing the resulting deletion mutants under a wide variety of selective conditions.
  • U.S. Provisional Patent Application No. 60/140,359 (filed Jun. 23, 1999) described methods of using tag arrays and the single base extension reaction for genotyping and other types of biological analysis.
  • a set of tags and a tag array derived from Seq. ID Nos. 1-2000 and their complements are suitable to be used for the methods described in this application.
  • the '359 application describes methods of determining the genotype of an individual at a polymorphic locus or the frequency of alleles in a population.
  • One embodiment of the method involves three step: (1) amplification of the polymorphic locus, (2) primer extension of a sequence-tagged primer with distinct labels for different polynucleotides at the polymorphic locus, and (3) hybridization to a tag array.
  • each distinct label can be determined at known positions of the tag array.
  • Each tag represents a distinct polymorphic locus and each distinct label represents a distinct allelic form at the polymorphic locus.
  • the method permits the simultaneous determination of a genotype at multiple loci, as well as the determination of allele frequencies in a population.
  • Another embodiment employs just steps ( 2 ) and ( 3 ).
  • Table 1 lists the sequences of the presently claimed invention. Column 1 lists the sequence ID number corresponding to each sequence. Column 2 lists the sequences in the 3′ to 5′ direction.
  • FIG. 3 shows the array features from the above-described array.
  • the array was hybridized with biotin-labeled oligonucleotide tags, stained with streptavidin-phycoerythrin, and the data was collected with a laser scanner.
  • Four features, organized vertically on the probe array, represent each tag-probe.
  • the brightest hybridization signal is seen with the “PM” feature.
  • FIG. 4 is a scanned image of the hybridization pattern resulting from the hybridization of 2050 different oligonucleotide tags labeled with phycoerythrin to an array designed as described above.
  • FIG. 5 is a scanned image of the hybridization pattern resulting from the hybridization of 50 sequences complementary to SEQ ID Nos. 2001-2050 to an array designed as described above.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

The invention provides a unique set of nucleic acid sequences which is appropriate for use for a wide variety of applications requiring nucleic acid tags. As such, the sequence tags of the presently claimed invention may be used, for example, to label biological and nonbiological materials, in genotyping applications and in a variety of other analyses.

Description

    PRIORITY CLAIM
  • This application claims priority of U.S. Provisional Application 60/195,585 filed Apr. 6, 2000 entitled “Tag Nucleic Acids and Probe Arrays”, which is incorporated herein by reference for all purposes in its entirety.
  • FIELD OF THE INVENTION
  • This invention provides sets of nucleic acid tags, arrays of oligonucleotide probes, nucleic acid-tagged sets of recombinant cells and other compositions. The invention relates to the selection and interaction of nucleic acids, and nucleic acids immobilized to solid substrates, including related chemistry, biology, and medical diagnostic uses.
  • BACKGROUND OF THE INVENTION
  • The use of short nucleic acid sequences as “tags” to identify specific biological substances in a sample is known. For example, tags may be used as a method of or as labels for a wide variety of biological and nonbiological materials, see, for example, Dollinger, The Polymerase Chain Reaction pp. 265-274 Mullis et al., editors (Birkhauser, Boston, 1994) or as a method of screening complex chemical libraries. See, for example, Alper, Science, 264: 1399-1401 (1994); and Needels et al. PNAS 90, 10700-10704 (1993). See also U.S. Pat. Nos. 4,359,353, 4,441,943, 5,451,505 and 5,654,413.
  • There is great necessity for sets of tag sequences which are known to hybridize effectively to their complementary probe sequences with minimal cross-hybridization between the different tag sequences. The presently claimed invention provides sets of tag sequences, tag sequence kits, and methods of using tag sequences which fulfill these requirements.
  • SUMMARY OF THE INVENTION
  • The presently claimed invention provides 2050 unique sequences which have been specifically chosen according to strict criteria to produce sequences suitable for a wide variety of “tagging” applications. These sequences are provided as SEQ ID NOs 1-2050.
  • In one embodiment, some or all of SEQ ID Nos 1-2050 comprise tag sequences. In a further embodiment, some or all of SEQ ID Nos 1-2050 comprise tag-probe sequences. In a further embodiment, the tag-probe sequences are immobilized to a solid support.
  • The unique sequences of the presently claimed invention may be used alone or in combinations of 10 or more, 100 or more, 200 or more, 500 or more, 1000 or more, 1500 or more, or 2000 or more as nucleic acid tags and/or tag-probes.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 shows a plot of the discrimination score and the signal intensity for 2200 candidate sequences.
  • FIG. 2 shows an example of the sequences attached to each of the four array features representing a given tag sequence. Four features, organized vertically on the probe array, represent each tag-probe.
  • FIG. 3 shows the array features from an array designed to probe for the tag sequences of the presently claimed invention. For each of the four tag-probes shown, arranged horizontally across the array, the brightest hybridization signal is seen with the “PM” feature.
  • FIG. 4 is a scanned image of the hybridization patterns resulting from the hybridization of 2050 different probes containing regions complementary to the SEQ ID Nos 1-2050 to an array comprised of tag-probes corresponding to SEQ ID Nos 1-2050.
  • FIG. 5 is a scanned image of the hybridization patterns resulting from the hybridization of 50 different probes containing regions complementary to SEQ ID Nos 2001-2050 to an array identical to the array depicted in FIG. 4.
  • FIG. 6 shows signal intensities from two different independent experiments in which 2000 biotinylated oligonucleotide tags or 50 fluorescein labeled control oligonucleotides were hybridized to arrays designed as described above.
  • FIG. 7 shows the PM/MM ratios from the data described in FIG. 4 above.
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS I. Definitions
  • As used herein, certain terms may have the following defined meanings.
  • As used in the specification and claims, the singular forms “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “an array” may include a plurality of arrays unless the context clearly dictates otherwise.
  • An “array” represents an intentionally created collection of molecules which can be prepared either synthetically or biosynthetically. In particular, the term “array” herein means an intentionally created collection of polynucleotides attached to at least a first surface of at least one solid support wherein the identity of each polynucleotide at a given predefined region is known. The terms “array,” “biological chip” and “chip” are used interchangeably.
  • The array of molecules can be screened for biological activity in a variety of different formats (e.g., libraries of soluble molecules, libraries of compounds tethered to resin beads, fibers, silica chips, or other solid supports). The fabrication of polynucleotide arrays on a solid substrate, and methods of use of the arrays in different assays, are described in U.S. Pat. Nos.: 5,143,854, 5,242,979, 5,252,743, 5,324,663, 5,384,261, 5,405,783, 5,412,087, 5,424,186, 5,445,934, 5,451,683, 5,482,867, 5,489,678, 5,491,074, 5,510,270, 5,527,681, 5,550,215, 5,571,639, 5,593,839, 5,599,695, 5,624,711, 5,631,734, 5,677,195, 5,744,101, 5,744,305, 5,744,992, 5,753,788, 5,770,456, 5,831,070, 5,856,011, 6,040,138 and 6,040,193 all of which are incorporated by reference herein in their entireties for all purposes. See also, U.S. Ser. Nos. 09/079,324, 09/122,216, and PCT Application WO US99/00730 each of which is incorporated by reference herein in its entirety for all purposes. Preferred arrays contemplated by the presently claimed invention have the probe densities as described in the above referenced patents. For example, the '305 patent discloses 100, 400, 1,000 and 10,000 probes/cm2. “Solid support,” “support,” and “substrate” refer to a material or group of materials having a rigid or semi-rigid surface or surfaces. In many embodiments, at least one surface of the solid support will be substantially flat, although in some embodiments it may be desirable to physically separate synthesis regions for different compounds with, for example, wells, raised regions, pins, etched trenches, or the like. According to other embodiments, the solid support(s) will take the form of beads, resins, gels, microspheres, fibers or other geometric configurations.
  • A “discrete, known location” refers to a localized area on a solid support which is, was, or is intended to be used for placement or fabrication of a selected molecule and is otherwise referred to herein in the alternative as a “selected” region. The discrete, known location may have any convenient shape, e.g., circular, rectangular, elliptical, wedge-shaped, etc. For the sake of brevity herein, “discrete, known locations” are sometimes referred to as “predefined regions,” “regions,” or “features.” In some embodiments, a discrete, known location and, therefore, the area upon which each distinct compound is synthesized is smaller than about 1 cm or even less than 1 mm2. In additional embodiments, a discrete, known location can be achieved by physically separating the regions (i.e., beads, fibers, resins, gels, etc.) into wells, trays, etc.
  • As used herein, a “polynucleotide” is a sequence of two or more nucleotides. Polynucleotides of the present invention include sequences of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) which may be isolated from natural sources, recombinantly produced, or artificially synthesized. A further example of a polynucleotide of the present invention may be polyamide polynucleotide or peptide nucleic acid (PNA). This invention also encompasses situations in which there is nontraditional base pairing such as Hoogsteen base pairing which has been identified in certain tRNA molecules and postulated to exist in a triple helix. “Polynucleotide” is used interchangeably with “oligonucleotide” is this application.
  • The terms “nucleotide” and “nucleic acid base” include deoxynucleotides and analogs thereof. These analogs are those molecules having some structural features in common with a naturally occurring nucleotide such that when incorporated into a polynucleotide sequence, they allow hybridization with a complementary polynucleotide in solution. Typically, these analogs may have one or more modified bases, as well as modified forms of ribose and phosphodiester moieties. The changes can be tailor made to stabilize or destabilize hybrid formation, enhance the specificity of hybridization with a complementary polynucleotide sequence as desired, or enhance stability of the polynucleotide.
  • The terms “nucleic acid,” “nucleic acid molecule,” or “nucleic acid sequence,” refer to a deoxyribonucleotide or ribonucleotide polymer in either single-or double-stranded form, and unless otherwise limited, would encompass analogs of natural nucleotides that can function in a similar manner as naturally occurring nucleotides. Nucleic acids may be derived from a variety or sources including, but not limited to, naturally occurring nucleic acids, clones, synthesis in solution or solid phase synthesis.
  • As used herein a “probe” is defined as a nucleic acid capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. As used herein, a probe may include natural (i.e. A, G, U, C, or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the bases in probes may be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization. Thus, probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.
  • The term “target nucleic acid” or “target sequence” refers to a nucleic acid or nucleic acid sequence which is to be analyzed. A target can be a nucleic acid to which a probe will hybridize. The probe may or may not be specifically designed to hybridize to the target. It is either the presence or absence of the target nucleic acid that is to be detected, or the amount of the target nucleic acid that is to be quantified. The term target nucleic acid may refer to the specific subsequence of a larger nucleic acid to which the probe is directed or to the overall sequence (e.g., gene or mRNA) whose expression level it is desired to detect. The difference in usage will be apparent from context.
  • The term “hybridization” refers to the process in which two single-stranded polynucleotides bind non-covalently to form a stable double-stranded polynucleotide; triple-stranded hybridization is also theoretically possible. The resulting (usually) double-stranded polynucleotide is a “hybrid.” The proportion of the population of polynucleotides that forms stable hybrids is referred to herein as the “degree of hybridization.” Hybrids can contain two DNA strands, two RNA strands, or one DNA and one RNA strand.
  • Methods for conducting polynucleotide hybridization assays have been well developed in the art. Hybridization assay procedures and conditions will vary depending on the application and are selected in accordance with the general binding methods known including those referred to in: Molecular Cloning, A Laboratory Manual, Second Ed., J. Sambrook et al., Eds., Cold Spring Harbor Laboratory Press, 1989 (“Sambrook et al.”); Berger and Kimmel, “Methods in Enzymology,” Vol. 152, “Guide to Molecular Cloning Techniques”, Academic Press, Inc., San Diego, Calif., 1987; Young and Davis, Proc. Natl. Acad. Sci., U.S.A., 80:1194 (1983), each of which are incorporated herein by reference.
  • It is appreciated that the ability of two single stranded polynucleotides to hybridize will depend upon factors such as their degree of complementarity as well as the stringency of the hybridization reaction conditions.
  • As used herein, “stringency” refers to the conditions of a hybridization reaction that influence the degree to which polynucleotides hybridize. Stringent conditions can be selected that allow polynucleotide duplexes to be distinguished based on their degree of mismatch. High stringency is correlated with a lower probability for the formation of a duplex containing mismatched bases. Thus, the higher the stringency, the greater the probability that two single-stranded polynucleotides, capable of forming a mismatched duplex, will remain single-stranded. Conversely, at lower stringency, the probability of formation of a mismatched duplex is increased.
  • A nucleic acid “tag” is a selected nucleic acid with a specified nucleic acid sequence. A nucleic acid “probe” hybridizes to a nucleic acid “tag.”
  • A nucleic acid “tag-probe” is a specific sequence capable of hybridizing to a specific “tag.” Typically, the “tag-probe” is the complement or a partial complement of the “tag.” In one typical configuration, nucleic acid tags are incorporated as labels into biological libraries, and the tag nucleic acids are detected using a microarray.
  • Throughout this disclosure, various aspects of this invention are presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention.
  • Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, the description of a range such as 4 to 50 should be considered to have specifically disclosed all integers within the sub-ranges such as 4 to 10, 4 to 20, 4 to 30, 4 to 40, 4 to 50, 5 to 10, 5 to 20 etc., as well as individual numbers within that range, for example, 6, 8, 15, 20, 32, 39, 43, 48 etc. This applies regardless of the breadth of the range. Likewise, a description of a range such as 1 or more, 10 or more, 103 or more, 106 or more, or 1012 or more should be considered to have specifically disclosed individual numbers within that range as well as higher numbers, for example, 20, 2×104, 3×108, 4×1015, 5×1018, etc.
  • Various patents, patent applications and publications are referenced throughout the specification, unless otherwise indicated, each is incorporated by reference in its entirety for all purposes.
  • II. General
  • The presently claimed invention provides 2050 unique sequences which have been specifically chosen according to strict criteria to produce sequences suitable for a wide variety of “tagging” applications. These sequences are provided as SEQ ID NOs 1-2050.
  • In one embodiment, some or all of SEQ ID Nos 1-2050 comprise tag sequences. In a further embodiment, some or all of SEQ ID Nos 1-2050 comprise tag-probe sequences. In a further embodiment, the tag-probe sequences are immobilized to a solid support.
  • An initial set of 2200 20 mer sequences was selected with closely matched melting temperatures. A further filter based on rules such as those described in U.S. Provisional Patent Application 60/176,520 was applied to optimized and standardize the hybridization characteristics of the set. Finally, sequences were removed if they were identical or nearly identical to each other or to sequences in the public databases. This reduced the pool of candidate sequences to 2200. The hybridization performance of the entire set of 2200 candidate sequences was evaluated. Labeled oligonucleotides complementary to the candidate sequences were synthesized and hybridized to an array containing probes designed to analyze the performance of all 2200 candidate sequences. The array contained four different sequences to interrogate each candidate sequence. A probe designed to be the perfect match complement to the candidate sequence (PM), a probe designed to have a central mismatch at position 10 (MM), and probes designed to be the complements to the PM and MM probes (cPM and cMM respectively).
  • FIG. 1 shows a plot of the discrimination score and the signal intensity for all 2200 sequences. A line was fitted to select the 2050 sequences with the highest discrimination and signal intensity. These 2050 sequences are SEQ ID Nos. 1-2050.
  • In one embodiment of the invention, the sequences of the presently claimed invention are tag-probes attached to a solid support. Methods of immobilizing presynthesized sequences and synthesizing sequences de novo on solid supports are known. See for example, U.S. Pat. Nos.: 5,143,854, 5,242,979, 5,252,743, 5,324,663, 5,384,261, 5,405,783, 5,412,087, 5,424,186, 5,445,934, 5,451,683, 5,482,867, 5,489,678, 5,491,074, 5,510,270, 5,527,681, 5,550,215, 5,571,639, 5,593,839, 5,599,695, 5,624,711, 5,631,734, 5,677,195, 5,744,101, 5,744,305, 5,753,788, 5,770,456, 5,831,070, 5,856,011, 5,744,992, 6,040,138, 6,040,193, U.S. Ser. Nos. 09/079,324, 09/122,216, and PCT Application WO US99/00730.
  • In this and other embodiments it is often useful to provide control probes. As one example, SEQ ID Nos. 1-2000 may comprise the tag-probes and SEQ ID Nos. 2001-2050 may comprise the control probes. In a preferred embodiment, the control probes are representative of the population with respect to observed signal intensities and discrimination. In a further preferred embodiment, tag sequences with relatively low signals may be over-represented in the control sequences so as to increase information about the sensitivity of experiments at the lower limit of detection.
  • METHODS OF USE
  • The use of short nucleic acid sequences as “tags” to identify specific biological substances in a sample is known. For example, tags may be used as a method of or as labels for a wide variety of biological and nonbiological materials, see, for example, Dollinger, The Polymerase Chain Reaction pp. 265-274 Mullis et al., editors (Birkhauser, Boston, 1994) or as a method of screening complex chemical libraries. See, for example, Brenner and Lerner, PNAS 89, 5281-5383 (1992); Alper, Science, 264: 1399-1401 (1994); and Needels et al. PNAS 90, 10700-10704 (1993). See also U.S. Pat. Nos. 4,359,353, 4,441,943, 5,451,505, 5,149,625, 5,654,413 and 5,800,992.
  • In addition to those applications above, the presently claimed sequences are suitable to be employed for any of the methods described in U.S. patent application Ser. No. 08/626,285 (filed Apr. 4, 1996), including as a method of analysis of genomic DNA. For example, as described in the '285 application, tag arrays may be used to identify the function of identified open reading frames (ORFs) by creating deletion mutants for each ORF and analyzing the resulting deletion mutants under a wide variety of selective conditions.
  • U.S. Provisional Patent Application No. 60/140,359 (filed Jun. 23, 1999) described methods of using tag arrays and the single base extension reaction for genotyping and other types of biological analysis. A set of tags and a tag array derived from Seq. ID Nos. 1-2000 and their complements are suitable to be used for the methods described in this application. Briefly, the '359 application describes methods of determining the genotype of an individual at a polymorphic locus or the frequency of alleles in a population. One embodiment of the method involves three step: (1) amplification of the polymorphic locus, (2) primer extension of a sequence-tagged primer with distinct labels for different polynucleotides at the polymorphic locus, and (3) hybridization to a tag array. The amount of each distinct label can be determined at known positions of the tag array. Each tag represents a distinct polymorphic locus and each distinct label represents a distinct allelic form at the polymorphic locus. The method permits the simultaneous determination of a genotype at multiple loci, as well as the determination of allele frequencies in a population. Another embodiment employs just steps (2) and (3).
  • Table 1, below, lists the sequences of the presently claimed invention. Column 1 lists the sequence ID number corresponding to each sequence. Column 2 lists the sequences in the 3′ to 5′ direction.
  • TABLE I
    Seq. Id 3′ to 5′ sequence
    1 TAAACTAGCATTGAGCCCAC
    2 AAATCAGCAAACGGGCTCCG
    3 GAATTGATAATCGCAGCCAC
    4 GATATAGGAATGGCGCATAC
    5 CTCATCGGAAGGGCTCGTAA
    6 ACAGATGGAAAGGCAGTTCT
    7 TTTGGTAGCTGAGTGCCCTA
    8 TAACTGGTTTGACGCCACGC
    9 TAATTGAGCTGACGGCGCAC
    10 TTGTTGCTACTCTGGCCCGA
    11 TTCCGTGCATAGTATAGGGA
    12 TTATGCGACTTATCTCGGGA
    13 TGTATAGGATTATGTCCGCG
    14 CTGCTAGGAATATGAGCTAC
    15 CTTCTGTCAATATGGGTACG
    16 TATTTCGAGATATGAGGCGC
    17 TTGATCGTAGATTCGTGAGC
    18 CGAGATTACAATTCACGAGC
    19 TGGTGTCTAGCTTCCAGCCT
    20 TGAGGTCACGGTTCATGCTA
    21 TGGTTACTGGTATATGCCGC
    22 CCGAGTGCAGAATAAACCCG
    23 GCGGTCTCAATACAAACTCA
    24 GAAGCTACCATACGCGAGCA
    25 ACGGGATAACAACGCAGCCT
    26 AGAAGATCAACAGCTCGTCC
    27 ATAAGATCAAGACCTGTGCC
    28 ATTAGATTAAGACCAGCGCC
    29 ATATAATCAAGACTGGCGCG
    30 AGCATATAACCACTGATCCG
    31 ACACTATTAAAGCTGCTCCG
    32 CAATGTATAAGACTCTCGCC
    33 CACTAATTCAGACGAAGCCG
    34 GACCCTATCAGACAGATGCA
    35 CACGCATCAAGACAGTATCG
    36 CAGCTCCTAAGACTTGGACA
    37 GGTATCATAGGACATTCGCA
    38 GGTTACATGGATATAGCACC
    39 TGTGTTTCAGCTATGCAGGC
    40 TAATTCGCTGCAACCAGATC
    41 ATAATTCCAACATGGGAGCC
    42 CATTGCTTAATATGGGAGCC
    43 CAATGCTTAATACCGACACG
    44 GATTGCTTAGACCCTGCACG
    45 GATTCATTAGACCAGGCGCT
    46 GATTCTACATGCCACTAGCA
    47 CCTGCGAACTGGCCTGAATA
    48 CGCAGCGGAAGGCTCAATAA
    49 CCTACCGCAAGGCAGGATAA
    50 CCTATGATAAGGCACGCACA
    51 CGCTGTGCAAGGCTCGTATA
    52 CGATTGTCAAGGCAGTGATA
    53 CATTGCGAACTGCATCTAAC
    54 GATAGTCCAATGCTACTGAC
    55 GATTCGGTAATGCGCTGTAA
    56 GACGTTTCAATGCAGCGTAA
    57 GAGAGTGCAATGCCGACTAA
    58 GAGATCCGAATGCGCGTACT
    59 CGAGATCCAAGGCCCATGAT
    60 AGCTTGCACAGTAACCATGA
    61 AGAGTTGAACAGCATACCCT
    62 TATCTGATCGGACGGCCAGT
    63 TATTGACTACTGCGCCTCAG
    64 TTGGACTATTGGGTATCGCC
    65 TTGTCAGATTGGATGCGCTC
    66 TATGCAGAATGGCGTGTATC
    67 CATTGGATAAGCACTGATCG
    68 CCCGGAATAAGGCCACGATA
    69 CTCATAGAATGGACCAGATC
    70 CATAGATTAAGCACTCAGCC
    71 CATGATGTAAGCACGCTACC
    72 CAGGAGCGAAGCAGATACTC
    73 CAGAGCAGAAGCACTCACGT
    74 TACATAGGCTTCAGCATCAC
    75 TATTATACCTTGATCCGCGC
    76 TAAACTGCTTGCATACGGCG
    77 TATAAGCCTTGCAGCGGACC
    78 TTTAAGCGGTGGATCTAGCT
    79 TTAATAGCCTTGAGCAGCGA
    80 ATAAATGCTTGGAACCCTCG
    81 GAAAGTTCATGGAATCGAGC
    82 GCAAGGATTTCGACTCAGAC
    83 CAAAGAATAATCGCTCCTCG
    84 TAAAGCACTTATGACTCGGC
    85 TTATAGCATTCTGTAGGCGC
    86 TCGCTGACATTTGATTAGCC
    87 CCTTGAATAATATCTCGGCC
    88 AGGTCCAGAAATTGCTGCAC
    89 AGCTCAGGAAATTCTAGCGA
    90 AGCTATGCAAATTAGAGGCC
    91 GGTAGGCTAATTTATGGCAC
    92 CTAATGCAATTCAATGCCGC
    93 CAACTGGCAATCAATACGCT
    94 CCAAGCGAATGCAACGTATC
    95 GCATAGCGAATTGGAGATAC
    96 GCATGTCGAATGGATGATAC
    97 GCACGTTCAATGGCTCGACT
    98 GCAGCGCAATCTGTCGAGTA
    99 AGCAGTGCAAATCCTGATAC
    100 AGCTTCGCAAATCTGGTACA
    101 AGCCTGCGAAATCTACTGAA
    102 GCAGATCGAATTATGGAGAC
    103 GCAGAGTCAATTATCATGCC
    104 CGTTAGGCAATACATTTCCC
    105 ACTGGTGCAAAGTCTTCGAC
    106 GGTATATGAATGTGTCGTCC
    107 GATAGTGCAATCTAGGTGAC
    108 GCAGTGCAATGGATGTACTA
    109 GCTAGGCTAATGTCCGGCTA
    110 GGTAGCCTAATGTGTGCTCA
    111 GGACGTGCAATCTTGTGACC
    112 GAGCGCCGAATCTAGTCGAA
    113 GGGAGCGACCTCTAGCTTAT
    114 GCGGGTCGAATCTCGCTTAA
    115 CGCCGCGCAAGCTGTATTAA
    116 CGGCTGCGAAGCTGTCTTAA
    117 CATCCGCTAAGATCGGTTAA
    118 CGTGCAGCATAATCCATCAG
    119 TGAGAGCTGGATCGCATTCC
    120 TAGGTGCTAGGATCTCAGCC
    121 TAGGTATCAGGATTCAGGCC
    122 TGCGCCAGTGAGTCGTATAT
    123 CAGCAACGTGGATCAACTAT
    124 CAGCGGCTAAGATCAATACC
    125 GCAGCCTAATCTGGCCTAGT
    126 GGGCCTGTACCTGCAATTCA
    127 TAGGCCGGACCTGCTGTTAT
    128 TAAGCCGCCACGGAGTGTTA
    129 TAAGGCTCTTGAGACGTAGT
    130 TAAGCCCGATCAGCATGGAC
    131 TTGCCCGTAGTCAGCTTAGA
    132 GAAGCACCGATCAGACACTG
    133 CAGGCACCAAGTAGCACAGT
    134 GGTGCGCCATGTACTCAGTT
    135 TCAGGCTTATCGAGCGCGTT
    136 GCAGGCAGATCGACCTAGTT
    137 GGATAGGGACTCAGATATAC
    138 GCATGGTTACCTACGCCAGA
    139 GGAGGCTGACTCATACGCAA
    140 GGAGCCTGACCTAGTCGATA
    141 GCGGCCAATTCGGCGATAAT
    142 GGTGCTCGACATTAGGCCAT
    143 GATCCCACATAGCGGACAAT
    144 GATCCAATCTGTCAGCACAT
    145 GAGCCAATCTGACTACCAGT
    146 TGCTGGATATGACTGTCGTA
    147 TGCTCTGCACTGCTGACGTA
    148 TCACCAGCCAGACTGTGTAG
    149 AGGAGCAACCATCATGCACG
    150 GGGCATACCTATCCCGAGAT
    151 CGGGCGATACCACTCAGATT
    152 AGCGGCAACCAGACATACGT
    153 CACGCCATACCAAGGAGAGT
    154 CAGTGCATACCAAGCGACGA
    155 CAGGCAGTACACAATCTACG
    156 TACGTCGCATCCATAGCTGA
    157 GAGTGACACCTCAGCAGATA
    158 CTACAGCACCTCAGGAGAGT
    159 CTCACGACATCCAGGAGTAT
    160 CCAGCACGACAGAGAGATGT
    161 CGCACACACCTGAGAGAGAT
    162 GCGCACGCACTCAGATGTAA
    163 AGACGCTCAACCACGAGAGT
    164 GACGCCACAGTCACTAGAGA
    165 GGCGCACACTGTACTCAGAT
    166 CGAAGCGCCAGTACCAGATA
    167 GGGTCGCTACCTACTCTGAT
    168 GAGACATGATCTACCAGTAC
    169 GGACGCTTACTCAGCAGTCA
    170 CGGGTGTTACAGAGCTATCA
    171 CGCGGCTTACACAGACATTA
    172 CGGAGCTTACACATTAGCAG
    173 CTGAGCATACACTTCACGAT
    174 CCGATCATAACTGTAGATGC
    175 CCGCCGATAACTGCTTGAGA
    176 GGCCATATACGAGATGTAGA
    177 CGTCCCTTAACGGCTGGTAT
    178 ATACCCAGAACGACTATGCG
    179 ATCCCACGAACGATGAATCT
    180 ATCCGCAGAACCGGCGATAA
    181 CCTCGCCGAAGCGTGTTTAA
    182 GCGCCGCACAGAGTCTTATA
    183 CGCGCTGCACAGAGCATATA
    184 CCGCTGACACAGGCAGATAT
    185 GCGTATGACCAGGTGTATAT
    186 CTGTATGAAGGTGCTGTACT
    187 GTTTCGCACGAGGATGTATC
    188 GTGCTCGCAGAGGATTTATC
    189 TAGGCCAGAGTAGCGACTTA
    190 CAGATCCTAAGAGCAGTTAC
    191 TAGATGCTAGGAGCGATTCA
    192 TAAGTCGGTGGAGCATATCA
    193 TAAGCGCGTGGACTCCTAAA
    194 TAAGTGGACTGAGCGCATAT
    195 TATACGGCAGTGGATCAGAT
    196 CTATACGCAATGCACTCAGA
    197 CTATCGTCAAGTGATGGACC
    198 TATAGACTAGGTGATCGAGC
    199 TAGTACGAGTGGGCATCAAA
    200 TAGACGTAGTGAGCATGACT
    201 TGACGAGTTAGGATCTATGC
    202 TTACGAGTGTAGCGTCCATG
    203 TCGTCGTAGCATCTCGCAGT
    204 TCGACGTAGGATCGCAGTAC
    205 TCAGTATCATGGAGTACGAG
    206 TGCACTAGATGGGATCGACT
    207 TGCGATTACTGCCGTCACGT
    208 TGGACTCTATGGCAGCCGTA
    209 TGACAGCAGTTGCAGTCCGT
    210 TACACAGGCTTGCAGCTCGA
    211 TGCAGCGGAGTGCCTCATTA
    212 GCGCAGGGAGATCCATATCA
    213 CGGCAGCCAAGTCCAGTATA
    214 CAGCGCCCAAGACGTGTATA
    215 GTGCCTGCATAGCGATAGTC
    216 TGCCTGCGAGAGCCTGTATT
    217 TGGCATCGAGAGCCGTTCTA
    218 GCAGGAGCAGAGCTTATATC
    219 GCGGGATCACGACGTTTACA
    220 GTGGCGATAGAGCATTCTCC
    221 AACGCGAGAAACCATTTGCC
    222 AGGCAGACAACTCAATCCGG
    223 AGGAGAGCAACCTACACTCG
    224 AGCCAACGAACCTACATGGG
    225 CCGCAAGCACGTCGAATGAA
    226 GCGCATGGACGACAAACGTA
    227 GCCAGGAGACGTAGATATTA
    228 GCGCATAGAGAGAGATCATC
    229 TGGTATATCGGTAGATTCGC
    230 GAGCTATAAGGTGGATTCAC
    231 CGCGGATAACTTGATTCACC
    232 GTCGGCTTACCTGATAGCGA
    233 GGAGCTATACATGCCTATCC
    234 GGTGCCGTACATGCTCGTAT
    235 TCGGCTTGACGTGCTCGTAT
    236 GGGCTGTGACTAGACTCTCA
    237 GCGAATTTAGTAGACGCACA
    238 GAATCTCGAATAGCGGTACA
    239 GACAGTTGACATGACAGTAG
    240 GACATTGACATCGCATACAC
    241 GAGTTTAGAATCGTGAGCAC
    242 CTATTCGCAAGTGTCGAGCC
    243 GTTATGGACACTGCTCGACG
    244 AGCGTTCTAAATGCGTCACA
    245 CCGATATGAACTGTCACTAC
    246 CGCGAATGAAGTCTACATAC
    247 CCACTATGAAGCGATATACC
    248 CACCAGTGAAGAGATACCGC
    249 GCACTGTTACATGATACCTC
    250 GCCAGTTACAGTCATGCCTA
    251 GCGCAGCTAGATCCACTGAT
    252 GCGTGCGGAGACCTCATTTA
    253 GCTCACGAGGCACGCTTTAT
    254 GCGCCAGTAGCACGCTTATT
    255 GGCTCAGTAGCACTCATCAT
    256 ACTTGCACAGCACAATACGT
    257 CGCCATACAGCACGATATTA
    258 CCGCAGACAGCACGAGTATT
    259 CCAAGGAGACTACACGATCT
    260 GCACAGGTAGCTCGACGTAT
    261 GTCAAGATGCTACCGTTCAG
    262 CGATATGAAGCTCAGTGAAC
    263 CCTATGAAGCTATCGCAACA
    264 CTTATCACAGCATCCGAGAG
    265 CCCGTGCAACGATTTGACAA
    266 CGGCGGTTAAGTTCTAATCA
    267 GGTCGAGCATGATAGCTTAT
    268 GTGGTAGCAGCATAGCTTAT
    269 TAGCGTGGAGCATCCTCAGT
    270 CAACGGTGAGCAACTATCAG
    271 CTGGTTCGAGCAATCTATCA
    272 TCGGGTCTAGGATGCTCTAC
    273 TCGATGCACTGATGTCACTA
    274 TCGTATATCCCATGCGATCT
    275 TACGGTCCAGCATCAGCTTA
    276 ATCAGTCCAACCTACAGATG
    277 ATCAACTGAACCTCATACGG
    278 TACTTCTGAGCAGGGAGCTA
    279 TAGTTATGAGCAGGCGTCCA
    280 CTTGTGACATCAGCCACGAT
    281 CACGGAGCAAGAGCACATCT
    282 CACGGGTGAAGAGCCATACA
    283 CAGGAGTTAATAGCTCATCC
    284 TAAGATTAGTTAGCAGCGCC
    285 GAGTGATTAGCAGACGCCAC
    286 CGATGATTACCAATGCCACG
    287 GACTGATTAGCACATCCACA
    288 GATTATGTAGCACTATGCCC
    289 GCTATATTACGAGCTATGCC
    290 GTTTATATCGAGGCAGGCCA
    291 GTTACTATCCGATCAGAGCG
    292 CGTCATGTACCATCAAGTCG
    293 GTTATCTACGGATCATGCGA
    294 CTGCCGTAAGTCTCATGCGA
    295 CTAGCCGAATACTGCATACA
    296 CTGCGTCGAGAATCGCGTTA
    297 CATACACGACAATAGCTTCG
    298 GATACCGACTCATACATTGC
    299 GATACCGCACGATCAGCAGA
    300 GTATATGCAGACTACTGGAG
    301 TATAGTCGATTATCCCAGCC
    302 CATAGTACAATATCCCGACG
    303 CTTGACAGCTACTACCAGTG
    304 CTGAGACAGCTATCGACACA
    305 CTGAGTAAGTCTTCCACACG
    306 TCGGATATACTATGCGTCAG
    307 CGTAGGATAGAATGCACAGT
    308 CATGATACACACTCACGAGG
    309 CGGAATCACGACTACATACG
    310 GGGTATCACGAGTCACCTCA
    311 GAGAGAATCGTATCACAGCC
    312 GAGTATGTAATCTACCTGCC
    313 GAGTAATCATAGTAGCAGCC
    314 GACTATATCCAGCACCGAGG
    315 GACATATAGCTCCACTCAGA
    316 TAGACCTAGTTGCAGCGCGA
    317 TACTACACGTTTCACGGCAG
    318 GTACATATCTGTCACGCGCA
    319 TAGTATATCCTACGCCGCTA
    320 GAGTATATCGCAATGCCAGC
    321 GAGTTGTCACATAGGCCACC
    322 GACGCATGACATATTCCTAC
    323 GAGACACTTGACAGTAGCCA
    324 GGCTAGTTACTCAGATCACA
    325 CGCAATAAGTCTAGCTCACT
    326 CATGTACTAAGCAGTCACAC
    327 CTAGTTAATGTCAATCCGGC
    328 GACTGTGTAATCATTGCAGC
    329 CGTTCGTGAATCAGCACAGC
    330 ATTCGGTCACACAGCACAGA
    331 ATCTGCTGACACACACTAAG
    332 AGCTCGCTAAATATGTAGGC
    333 ACTGTCGCAAATATCACACG
    334 ACTGTCTGACCAACCAATAG
    335 GTTACTAGCTGGACCTCAGA
    336 TTATAGACTGGTGCGGAACA
    337 TTAGCATACTGTGCGCGAAC
    338 TGTGCTGACTTAGGTCGAAT
    339 TCTCGGGACGTTGCGCTATA
    340 TGTCCGCGACGTTGGCTATA
    341 TGTTCGTGACTGTGCGCTAC
    342 TGTCAGGTACTGGTCGCTAC
    343 TTCATGTACTGTGGCTACCG
    344 TTTACTAGAGTGGCGCATGA
    345 TTAGATAGATGTTCGGCCAG
    346 CTCAATAGATTATAGGCGCG
    347 TCGAATCGCTGTTACGGAAA
    348 TCAGACTAGGGTAGCGCATA
    349 TCAGCAGTATGTAGGCAGTA
    350 TAAGCCGGGTCACGCTATTT
    351 TATGACCGATGTGCAGGTAT
    352 TTAGCACGCTCGGCGATGTT
    353 TTCACACGGTCTGCGAGCTT
    354 CTTCAGACAGGAGGAGATAT
    355 TCCAGCCGACGTGCGATTTA
    356 TCCAGCGTACCTGCTTGTAG
    357 CTCCAGTCAAGTGCTTCGAG
    358 CTCCAGCGAAGTGATGAGAA
    359 TGTCAGCGGATCGCCATATA
    360 TCCATGCGAGGATCAGGTAT
    361 TGCAAGCAGTTCTCAGCGTA
    362 TGTAGGACCTGTGCTCACTG
    363 TTTATCGCAGTGCTCAGGCT
    364 TATGTCAGCAGGCCCAGCTT
    365 TTCTCGTAGCTGCGCCTAGT
    366 TATTCGAGCTAGGGACGCAT
    367 TATTTATACTGCGAGCGAGG
    368 GACCTTACACTGGCACGAGA
    369 TACTGATAGCATGGGACGTT
    370 TCGGATAGCAGTGCGCTCTA
    371 GCTGATGCACGAGGCCATTA
    372 GCTGGATCACGAGGCTCATA
    373 CGCTTTGTACCAGGCCATAG
    374 CGTGATTGACCAGACCCAGT
    375 TACGCTGGATCAGACGGTCA
    376 ATCCTGAACGCAGAGACACG
    377 ATCGTTGCACCAGAACTACA
    378 CTCTCAGGACCAGCATGATA
    379 TCTGAGCGATCTGCCAGTCA
    380 GGTGAGACCTATGTATATCG
    381 TTAGAGTCTTAGGCATGTCG
    382 TTATAGCCGTAGGCAGGTAC
    383 CTCTAAGTATTGGACACGCA
    384 GCTAGGATATAGGACACTGA
    385 GCTATCGAATGTGCAGTACG
    386 TCTATCCACTGCGGACGAGT
    387 TCATACTCATGTGCAGCTCT
    388 TCATCGAGATCGGCCACTGT
    389 CTTATGATACCAGTCAGCAC
    390 TATTGGTACGGAGTTAGCCC
    391 GTAGATGACCCAGTTCCAGC
    392 GGCTGTTACCGAGTCTCAGA
    393 TGCTAGTTAGGAGTATCGCA
    394 GGCTTACTAGCAGTCACGCA
    395 CAGCATATAAGAGTCGTACC
    396 GGCATCATAGACGCTACGCT
    397 GAGTCAGCAATCGCAGCTAA
    398 GATCAGTAATGCGGAGCAAC
    399 TATCATAGATGCGGACGGAT
    400 CAGTCCACAAGCGCGAGTAA
    401 CGTAGCCCAAGTGCCGATAT
    402 GACGCACCACAGGCTAGTAT
    403 CTAGCATACCAGGCGAGAGT
    404 AGTGCATCACAAGAGACTCG
    405 GCCATAGACGAGGCAGTATC
    406 GGAATACGCTGAGATATACG
    407 GTTAATCGCTCAGCAGCATT
    408 CACAAGCGACCAGAAGCGTT
    409 TCTTATCGACCAGGGCGGTT
    410 GACACTATCCCAGACGGAGT
    411 TTACTAGGTTCAGCGCGATC
    412 TTCAGATCCTCAGCGTAGTC
    413 TCTCAGATATTCGTAGCAGC
    414 TGTCTATTAGTAGCTGCGAG
    415 TAGATACTCTGAGCTAGGAG
    416 TGTCTCCAGATCGTGCGAGT
    417 TTCGGTCTAGCTGGTAGCAT
    418 ATCTGGCGAACAGGTGCATA
    419 AATGCGCGAAACGGCGATAC
    420 TTTGTCGCAGTAGTCGCATC
    421 TGTTGTGCAGTCTCCAGGCA
    422 CATTGTGAACTCTACGTCAG
    423 CGGATGTCAAGCTCTCACAG
    424 CTGCGGCAATACTCTCAGGT
    425 ATGCGGAGAACCTCTGACAA
    426 GCGCGTGAATCCTGTGACTA
    427 GCGCTCTGAATCTGTGAGAA
    428 GCGCTATGAATGTCAGCTAA
    429 GCCGAGGTAATGTGATATAC
    430 GCCGCGTGAATATGAAGATA
    431 GCGGCGAGAATCTTCCGATA
    432 GATGGTAGAATCTCTCTCAC
    433 GCTGCGGGAGACTATCATCT
    434 GCTGGATTACGATGCCATAG
    435 GTTGATTCACGATGGCAGAT
    436 CTTCACGCAAGTTGTCCAGA
    437 CTTACGCCAAGTTGTCAGAA
    438 CTTGCGTCAATAGTCTGAGA
    439 CCTGTGCGAACTGTCTTACA
    440 CTCAGTCCAAGTGGCTCAGA
    441 CCATAGCGAAGCGCACAGTA
    442 CCAGCACTAAGCGCAGATAG
    443 CTCCGCCTAAGTGGCAGTAA
    444 TGCGCCTGACGTTCGGATTA
    445 TGTCCAGTAGCTTGAGAGTC
    446 GCTCACAGAGTTTGATAGAC
    447 GCTACAGGAGTGGATATTAC
    448 GTGACAGTGGCAGATATAAC
    449 TCGCACTGAGCTGTAATCGA
    450 TCTTATGAGATGTAGCTCGC
    451 TCCATCTAGCTGTAGCCGAA
    452 GTCATAGCAGCTTAGACCTA
    453 TTATGCTGACTGTGCTCGAC
    454 TTAGTGCAGTATTAGTCGCG
    455 TGTCTGACCTTGTAGCCGAC
    456 TGTTGACACTTGCGTACCGG
    457 TCTTAGCATGTGCGACGACG
    458 GCTAAGCTCTTGCACTGACG
    459 CATAAGACTTTCCAATCGCG
    460 CTGAAGCACTTTCCACGAAG
    461 CTGAACCCGTTGCAGAGAGA
    462 CGGAACCGATGGCACAATAT
    463 GGTGACCGATGGCTACTCAT
    464 ATGGCGCGAACCCTGTACTA
    465 CATCGCGGAAGCCACGTATA
    466 GACGGCAGAATGCAGTATAT
    467 CGCGGAAGAAAGCATATTTG
    468 CTCAAGGGCACGCAATCTAG
    469 TCACAGGAGGCTCGACTCTA
    470 CGACAAGGCATTCACACTAG
    471 ATAAAGGTCATGCCAACCGC
    472 TATAATGCGTTTCACGTCCC
    473 TCTAATGCCTGACACGAAAC
    474 TGAATGCCGTGACTCGTAAA
    475 GTGGAGGCACTGCATCATAA
    476 GTGGTGTGACCTCGCCATTA
    477 GGAGATGCACTACGGACTAT
    478 GAGGATCGAATACTGTCGTA
    479 CGGAGAGCAAGTCATACGAC
    480 GCAGGAGACGGACTATACTA
    481 GAGCGTGTAATCCGATCTAA
    482 CGATACGGAAGGCGCACTAA
    483 CGATAGGTAAGGCGACTCAA
    484 GATGTGGCACGACGATCATA
    485 TGAGTAGGCAGTCCGATCTA
    486 TGATAGGCAGTGAGTTCATC
    487 TTATGGCGAGAGTTGTCATC
    488 GTTTAGGCACGATGCTGTAT
    489 GCGTTAGGACCATAGTCTAC
    490 CCGATGCGACAATACGTTAG
    491 TCTAGCGTCCCATAGCGTAG
    492 CTGTCTGGACCATAGCAGCA
    493 CTGCTTGCACGATGAGCGAA
    494 TAGCCCGGACGATGTAGTCA
    495 CCGCTACAAGCATTGGGAAT
    496 CGGCTAGAAGAATGAATGCT
    497 CCGATGATAAGCTAGTATGC
    498 GCGGATAGACCATTATTGAC
    499 GCCACTAGACCATCGGTGAT
    500 GCACGCGGACCATCGTTTAT
    501 GCCGCTCGACCATAGTGATA
    502 GCCGAGTCACCATGCTGTAT
    503 CACGGGTCACCAAGCGTATT
    504 GACGGCGACCCAGGTTATAT
    505 TGTGCGTCAGCAGTTAGTAT
    506 GCTCGGCTACCAGTCGTTAT
    507 CGCTGGACACCACTGTGATA
    508 CGGTGGAGACCAGATTATAT
    509 CGCGGGACACCAGCATATTA
    510 GCTCGCGCATTAGCATATAA
    511 GCTGACATCCACGCATTGAG
    512 CGCTGATCCACCGAGATTAG
    513 ACGCAACCAACAGCGAGTGT
    514 CACAGACCACAAGCTATGGG
    515 CCTAGCCCAAGGCATTAGAA
    516 CCGTAGCTCCAAGGCATGTA
    517 CAGTGCGCCAGAGCAAGTAA
    518 GAGCCACCACGAGTCATGTA
    519 GGTCACCACTCAGCGATGTA
    520 GTGTGCCACTAGGCCGATTT
    521 GGAGACCCGTAGGCATAATT
    522 CGCTGTAAGGATGCTGAATA
    523 GTCGTGCAGGATGCCATATT
    524 GTTCCGCACGATGCCAGATT
    525 GCTGCGACCATCGTCAGATA
    526 GTCTAGCGATCATGCTCAAT
    527 CTCTACGAATCATGCGGAAG
    528 CTTAGATACTACGAGCACGA
    529 GTGACGCTACGTGAGCCTAA
    530 TACCGTGTACGTGAGCGCAT
    531 TACTGCGACGTAGCGAGTCA
    532 TACTAGGTACTCGCGGCACT
    533 TACTGCGTACTCGGAGCATA
    534 GCTCACGTACTCGACAGAAA
    535 GTGTACTATGTAGCGAGATC
    536 TAGTAGTACGCTGTCAGAGC
    537 TGTCGTCGAGTCGTAGATAC
    538 GTAGTACACGGAGTGATCCT
    539 GTAGTACGAGCTGAGACTCT
    540 GTGACTAGCTCGTAATTCTG
    541 GAGACACGGTACTAGAGACT
    542 CAACAGCGTCACAGACATGG
    543 CTATGAGACCACCTCGATAT
    544 ATTCGGCGACAACGCATTTA
    545 GTTGCCGTACTAGGGATACT
    546 GGCGCAGTACGATTGACTAT
    547 GTGCGACGAGCTTGTCACTA
    548 TGCGTGTGACTATTGATACG
    549 CGTCTGCGAACTTTGCTACG
    550 CTGTAGCGAAGTTCTCATAC
    551 TCGGCGTTACGTGCTGACTA
    552 TGAGCTATACTCGTCGTCAG
    553 CCGATACTAAGCGTTACGAA
    554 CGTCATACATAGGACTAGCA
    555 CGCACGCTACAGACTATTAT
    556 GCGAGCGTACTATACATAAC
    557 GCGAGTCTACGACCTCTATA
    558 CGGTACGCACGACAGTCATA
    559 CGGTACATACGACTATACAG
    560 CGCTAGATACACCACTGATA
    561 CTCTAGGTACACTACTGCAT
    562 CGTCAGAGACACTGGAATAG
    563 CTGCGCGTACACTCGGATAT
    564 CTGTCGCTACACTCGTGAGA
    565 GTAGACGCCTAGTCAGATAG
    566 GAGCGACTACGAGCCACTAT
    567 GTGCGACTACGTGCATCACT
    568 CGTAGGACACGAGCGTATAT
    569 GGCGACGACGTGACTATACT
    570 CGGTCACGACGACGAGATAT
    571 GCGTCACACGAGCCGATATT
    572 GTCGCTCACGATGCGGATTT
    573 GACCGACAGATCGTGACATC
    574 GACCACGTACATGAGCTGAC
    575 GGCGACGTAGATGATATTCT
    576 GAGACTGTAATCGCATATCC
    577 GACTATGTAATCGAGCCTAC
    578 GATAGTCGAATCGCGGATAA
    579 TATACGGACTGCGCCCTAGA
    580 TAGTCTAGCTGAGCCATCGA
    581 GTATATGACCTAGTGCCACG
    582 GTGTTGTACGATGTGCTCCA
    583 GAGTCTGACATAGGGCACCT
    584 GAGTTGCACGTAGACGATAC
    585 GACTCGCGCATAGACACATG
    586 GACAGGCTACGAGACTAGAT
    587 GTGACGGCACTAGCAATATA
    588 CTGCTCTGACACGCGAGTAT
    589 CGGCTGTGACACGAGCTATT
    590 CTGGTGCGACACGCCTATAT
    591 GTCAGTGGACTAGCCCTACA
    592 ATCGAGTCAACCGGCCTAGA
    593 TCGATAGCCTACGTGCCGTT
    594 GGAGACCTCTACGCACTGTT
    595 GCGTGACAGCTCGCACTATA
    596 GCGTAGCTCAGCGACATTAA
    597 GCTATACGCACCGTCATGTA
    598 CGCATACACTCAGCAGAGAT
    599 CTACTTACAGCAGCGACGAG
    600 ATCTCGACACAAGCTAATCG
    601 CATCGGATACACGCATACAG
    602 ACATACAACACCGCTTAGGG
    603 TACTGAGTCCACGCTCGGTA
    604 GATACAGCCTACGACCGGAT
    605 GATACATTACTCGACACGCG
    606 CGCTACAGAGATGCACAGAG
    607 CCGACTGTAACTGCGATGAA
    608 GGTGTTATACGTGCATAGCC
    609 CTCGTATTAAGTGCGCTACC
    610 TATAGTATCGAGGAGCGACC
    611 GTATAGTACGTGATAGGCTC
    612 GTACGATACGTGACTAGAGC
    613 GTAGGTCGAGCTGCATACTC
    614 TTACAGTAGTCTGCATCCCT
    615 CTAGTCAAGTCTGCATACAG
    616 CTGTCTAATACGGCCACATA
    617 CTCGCAATACGTGTACCGTG
    618 TCCGATCTACGTGACGGTGA
    619 TCTCGCCGACGTGGTCTTAA
    620 TCTGTCCACGTCGCGGTTAT
    621 TCGTCCTGACTCGCTGGTAA
    622 GTCCCTAGACTCGCAGTGAT
    623 GCGACAGTAGCTGCAATGAT
    624 GACGTAATATCGCCACATCA
    625 GACGAGGTACAGCGCATACA
    626 GCAGGTCTACGACGCATGAT
    627 GCAGAGTACGGACGCATATC
    628 GAGTAGATACAGGTCACGAT
    629 GAGCGATCACACGTCCGATT
    630 GGTCGCATAGACGTATCAGT
    631 GGTGTCTCACGAGTATCGAC
    632 GTAGGCTAGACGGTCCACTA
    633 GACGGACACTGAGCACATAG
    634 GACACCTATGTAGCAATGAC
    635 CACAGTACAATAGCACCTGG
    636 CACCAGAACGTAGGCACAGT
    637 CACTACTCAAGAGCCAGTTA
    638 CGCCGACGAATAGCCAGATA
    639 GCCGCACTACTAGCGATGAA
    640 GACCAGTTACGAGCAGCGAA
    641 GATCACGTAGGAGCACCGTA
    642 GTACGCAGAGGAGTCATCCA
    643 GTCGCTGACTAGGATCACGT
    644 TACGCAGACTCGGACTCGAT
    645 GTCGCTATATCGGACCTAAC
    646 ACTCGCATAAACGACAGTCT
    647 TGGAGTCGAGTAGTACATAC
    648 TACGACATGGTAGGACGCTA
    649 TGACTTCTACGTGGCGATAT
    650 TACGCTCCGAGAGGCGATTT
    651 CACCTTCGACGAGCAAGAGT
    652 TACGCTCGCTCAGCTTAGGT
    653 TACGGCATCGACGCTATTGC
    654 TACGGCGACTGAGATGCCAT
    655 TACGTGCTAGGAGATGTAAC
    656 TATCGTCTATCAGATTGCCC
    657 TATCGTATCCACGTTCCGAG
    658 GATCGTACATCAGTGTCCAC
    659 GAGTCTATATCAGTAGCGAC
    660 GTTAGTCGATCAGTAGAGCA
    661 GTCCTACGATGAGTGACGCA
    662 CGTCTTCTAAGCGTGCTGAA
    663 GTCTCCTACCGTGAGCAGTA
    664 ATCTCACTACAAGAGCCTAG
    665 CTGTGACGACCAGACGCTTA
    666 CTGAGCGTAAGTGATTGTAC
    667 CTCGTAGCAATAGATTTCCC
    668 CTACGTGCAATAGCAGCTCA
    669 CCGGCAGTACAGATAAGTCA
    670 CGCCGGATACAGAGTAATCG
    671 CTCAGCATACATAGTACAGC
    672 CCGAGCTTACAACGTGTGCA
    673 GACGCATTACCACTGGCGAT
    674 CAGGGTGTACCACGAAGCAT
    675 CGGTGTTTACAGCAATCCAT
    676 CTGGCTGCAATAGCGCGATA
    677 TGGGCTACAGTTGCGCTCAT
    678 TCTGGCATAGCAGGTGTCAC
    679 GGGATTCTACCAGTTCGCAC
    680 GAGGATGCAATCGTAGTCAA
    681 AGGGATAACCATGCACACCG
    682 CATGAAGACTTTGCACTACC
    683 CGCCGACCAATGGGCATATA
    684 CCCGAGCCAACTGGAGATAA
    685 CCCGCAGCAACTGGGATTAA
    686 GCCATAGGAGCAGCGATTTA
    687 CCGCTTGCAGCAGACGATAT
    688 CCGTTTGCAGACAGCCAGTA
    689 CCGTTTACAATGAGCACACA
    690 CGTTCTTTAATGAGCGACAG
    691 CGAGCCTTAATGACGCACAA
    692 GGCAGCATACTCACGATCAT
    693 CTGCGAGCAATCAGCCGATA
    694 CCGCAGCAAGCTATCGAGAA
    695 CGGCGTTCAAGCAAACCGAA
    696 CAGTTTACAAGCATATCCCG
    697 CATTGACGAAGCATAGTTCC
    698 CATAGTGCAAGCAGCGACAC
    699 ATCTGTGCAACCATAGTACC
    700 ACTTGAAATGAGAAGCCCGT
    701 CAGGAGAAGCGAATAGCCTC
    702 CCAGAGAGAGCAATATCCGC
    703 CAAGGAATATACAGGCCCGC
    704 CAGAACTGAATTACAGCGCC
    705 CATCAGACAATTACAGCTCG
    706 CACCCGATAAGAGCATACGG
    707 CACTCCAGAAGCACGATAGG
    708 CAGCACCGAAGCAGAAGTCT
    709 CAGATCAGAAGCAGGACGCT
    710 CAGACCATAAGCACAGGCGT
    711 ACAACACAAATGGCGCGGCT
    712 ACGCAGATAAATCACCTCGG
    713 CAAGACAGAATACTCTCCGG
    714 CACAATACAATAGGCTCGCG
    715 CAATAAGACATAGGCCGCCG
    716 CACAACGGATTAGAAGCGCG
    717 GACATGATATGAGAATGCGC
    718 AGCAAACTAAGAGCCGGGTC
    719 AACAATACAACCGTCGGCGG
    720 AAATAACTAACCGCCTGCGT
    721 CAAACACGAAGAGCCTGTCG
    722 CACTAATCAAGCGACAGGCG
    723 CATATACCAAGCTATCAGCG
    724 CACATTCAAGACGATCACGT
    725 CACCTATGAAGAGACTCACG
    726 AACTATATCAAAGCCCTGGC
    727 ACAATACCAAATGCGCCGGG
    728 AGAAACGCAAATGCCTCTCG
    729 CGAAAGCATAATAGCGGTGC
    730 GGCAGAATCTCGTGTACTAG
    731 GGTACATTATGCTAGAGAGC
    732 GATACATGATGATAGCAGCG
    733 AGAACAGGAACATCGCTGCC
    734 AGATAAGCAACATCCTGTCC
    735 CATAAGCTAAGATCCTGGAC
    736 ATTTAGCGAAGAAGCATGGC
    737 ATAGCTCAATCAACGATGCG
    738 TATATCGCATCCACTCTGGG
    739 CATCTCCGAAGCACATTGAG
    740 CATTCGTCAAGCACTTCAGA
    741 CATTATCGAAGCACGGTACA
    742 GATTCGGACAGCACGGCATA
    743 GCTCCGGCAGTCACGATTAA
    744 GACTGTCGAGCACCCATTGA
    745 GATCGTCGAGCACGCCTAAT
    746 GAGGTCAGACGACGCCTATA
    747 GCGCGTATAGCTCTCCATAG
    748 TAGCGAGTAGCACTTCGATA
    749 CTAAGTGTAGCACCACATCA
    750 GTAGATCGAGCAGCCAGTCT
    751 GACATAGACCATACCACGTT
    752 CGTCTTCGAGCAAGTGCAGT
    753 CTCTCCGGCAGCGATATGTA
    754 CCCTCAGCACGAGATATAAG
    755 CCCTTGCGAAGCATTGCGAA
    756 CTCCAGGCAATGAGAGCACA
    757 CCCAGATCAAGCGATGCAGA
    758 CTGAATCCAATGTACGTGAC
    759 CGGCATTCAAGGTAGCGACA
    760 GCCCGATTAAGGTGTGTCAA
    761 GCCCGATCAATGGCTGCATA
    762 CGCCATCCAAGGGCTGTATA
    763 CGGATGCCAAGGGCTTCATA
    764 GGTTGCGCCAGGTCATCTTA
    765 GGTCCGGCATGGATCACTAA
    766 GGCTGGCACATGATCGTATA
    767 TGGTTGCACTTGGATCGAAA
    768 TGATTGCCACTGCTCATACG
    769 TGTTGATCCATGTCCATAGC
    770 TTAAGGCACTTGATCTCAGC
    771 GTAATGCCCTGGACCGCAAT
    772 GTTAAGCCTTCCACGGCAAT
    773 GTTGCGCCATTGAGCCAGAT
    774 GTTGCCCACCTGAGACGTTA
    775 AATGCGCCACAAAGCGAGTG
    776 CACCGGCCAAGAAGTACAGT
    777 CATCCGCCAAGCAGAGTGAA
    778 CGTTGCCAATGCACGAGCTA
    779 GATGGCTGAATGACGTTTAC
    780 GATTGCCTAATGAGTCTGAC
    781 AATCAGCCAAAGATGTGGGC
    782 AATCATGCACAAAGTTCGCC
    783 ATTTAGGCAAGAAGCGCACC
    784 AATTGGCTAAAGAGCGCACC
    785 ACATTGGCAAAGCGAACTCC
    786 AATGGGAGAAAGCCGACTCT
    787 TGTGCTGGAGCTTCAGTCAC
    788 GTTGTGCAGGATTATCGACA
    789 GCTTGCAGACGAGTCATCAC
    790 GGATGGATACTAGCGACTCC
    791 GCTATGGCACAGGCATCTAC
    792 GGACTGGCACATCCCGTATA
    793 GGATCGGACCATTCTCACTA
    794 GGATGGCGACATGCTCACTA
    795 GAGCTGGCAATCGTCGTACT
    796 GGATGGCTACATGATCTGAT
    797 GGCAGCAATTCGGGCTAATA
    798 GCCTAGCAATGTTCCCAGAG
    799 GAGCGGCAATGATGATCCAT
    800 TGGTGCATAGCTGCGATCCA
    801 GGCTGCACAGGTGTATCCAA
    802 GAGATGCCAATCGGCCATAA
    803 TATATGGCACATCGTTGCGA
    804 TGATGCCCACGTCGTCGTAT
    805 ATTGATCCACACACAGTACG
    806 AGCTGATCCAAGCAACGTAC
    807 GTTGATGCAGATCGCGTATC
    808 TCGTGGGCAGATCGCTTCAT
    809 TGTGGCCGAGATGCCTTCTA
    810 TTTGCGGACTTCGCTATCAA
    811 TCCCATGCACCTGAGTGGAT
    812 TTTCATGGAGCTGTCGCGTA
    813 TTTACCTGTGGTGATAGCGA
    814 TTGTCATGCTGCCCAGTCGA
    815 CTTTCATGCAGGCAGAGCCA
    816 CCTTTAAGCTGGCACACGAT
    817 CCTATCAAGGATGCACACGA
    818 CCGTTCAGAATATGACACAC
    819 TAGGTCAGATCATGCGCGAC
    820 ATGTGCATACAAGCTACGAC
    821 CTGAGAATATGAGAGACGCC
    822 ACTCACGCAAATGAACGGCG
    823 CTTAGCGAATATGCGATACG
    824 ACTCTGATAAATCCGACACG
    825 ACTGTGCGAAATCCCAGACA
    826 ACTGATGTAAATCCACACCG
    827 ACGTGAACAATTCCACACTG
    828 ACTGCACGAAATCGACATCG
    829 ACTTCTGTAAATCGCAGCAC
    830 CTGTCTTGAATAGCGATCAC
    831 ATGCGGTTAAGCGGTAATAC
    832 TACGCTGAGTCATCCGAATA
    833 CTTGTGAGACACTCCGACAT
    834 CTGGTGACATACTATCAGAC
    835 CGTGCGTTAAGCTGTCGATA
    836 CGGTATCGAAGCTGTGCTAA
    837 CGCGTGTGAAGCTGCCTATA
    838 CCTAGTAGAAGCTCCACAGA
    839 TGTGTCGGAGTCGCCCATAT
    840 TCTGTCGAGGTAGGCCATAT
    841 GCTGTCGAGAGCGATCATCA
    842 GCAGTCGGACGAGATTCTAC
    843 GCGATGGTACTAGATCAGCA
    844 GTGTAGGGACTCGTATCACT
    845 GTACGAGCAGTTGAGCATAA
    846 GTCAGTCGAGATTCAGCAGT
    847 GTCGAGTCAGATGCACGTCA
    848 GTGTATCTAGCTGCACGCAC
    849 GTTGTCTTACGTGCAGTCAG
    850 TATGTACTCGTATCGACGCA
    851 TCGTGTCGAGTATCCGCAAA
    852 GTACGTTGACAGTCTGCACA
    853 TTCGTAGAGGTCTGCCAATT
    854 ATTCTGAGAGACAAGCCTCC
    855 ATTCTGACACAATCATCGCG
    856 ATTCAGAACTAATGCACCGC
    857 AGGTATGAACCATCGCACAC
    858 ATTTGATGAACTCCGCAGAC
    859 GTTTGCTGACCTCGCAGTCT
    860 ATTGCCGGAACGCATTATAC
    861 TGTGTGGGATCGCCCTATCT
    862 TTGAGTGAGCTGCGCTTATA
    863 TGCGTGCAGGTGCCACTAAA
    864 GTGCTGCATGAGCCAGTTCA
    865 GGCTCTACATGGCGATAGCA
    866 GCTCTCTAATTGCGGACACA
    867 GGATATAAGTTGCGGCACTA
    868 GGATGTAATGGTAGCTCCTA
    869 GGATGACGAGGTCTCACCAT
    870 GGATGCGACGATCTCGACAT
    871 CGTGATCGAAGGCTGCACAA
    872 CTAGATGTAAGTAGCTGGAC
    873 CGAATGAAGGATCGAGACCT
    874 CGGCCTGGAAGTCACTCATA
    875 GGCCTTGGACTACCGCTTAA
    876 TGCTTCGAGGGTCCCACTTA
    877 TGCCTGGTACTGTCCGACTA
    878 TGCTTGTGAGAGTCGCTACT
    879 ATGCTTGCAGAACCGTCAGC
    880 TGACTGTAGGGAGCCTCAAC
    881 TGCTTGGCAGGATGTCTTAA
    882 GGCTCCGGCATGAGTATATC
    883 TGCTTTGCAGTGAGGCTCTC
    884 CAATTTGGAACTAGCCTTCG
    885 TTTGCTGCATCCGGCCTGTA
    886 TTGGGCCACTGCGCTCTTTA
    887 TGTGAGCCCTTGGCACGTTA
    888 GGTGGCCCGATCACATTCAA
    889 GGCAGGGCACCTCAGTTTAT
    890 GGGTGGCCCATGCTATCTAA
    891 GTCTGGCCCTACCTATGGTT
    892 GCGGGCACACCTCTGATTTA
    893 GCGGGCGCACCATTCATTAT
    894 GGAGCCCACCATGAGCTATA
    895 GAATCTCCACCAGGCGGATA
    896 GGATACGTCGCTACAGTGAT
    897 TCGTATAGCTGTATCGACGG
    898 CTAACTAGCTGTAAGCGACC
    899 ACTAGATAACAGATGCGCCG
    900 CAACTATCATCAAGACGGCG
    901 CAACAGAGATGAAGCGCGTC
    902 CAACATATCATAAGCGCGTC
    903 GCAGATAGCATCATATACGC
    904 GCAGACTGAATTAGCTCTAC
    905 GTTAATTCATCTAGCGCGAC
    906 AGGAATCTAACCACGCGCAG
    907 AGACCAATAAGCACCCTGGG
    908 AGACAAACATTCACGCCGGG
    909 AGAATAAATTACTGCCCGGC
    910 GAGCACATATTATTACGCCC
    911 CAGAAGATAATATGCTCGCC
    912 GAATAGCCGATAATCTCAGC
    913 GAATAGCTTTACACTGCCCT
    914 GAATCACTCTGAATGAGCAC
    915 GGATCACACTGCCGGACTAT
    916 GGACCCATAGCACTCTGATT
    917 GAGGCATTAGCACCAGCTCT
    918 GGATTATCAGCACTCAGTAC
    919 GGGATCTCAGACGATGCTCT
    920 GGGTATATCAGCGGATTCCA
    921 GCAATTCGATCTAATGCTCC
    922 ACCAATGCAAATAGGCGGCC
    923 AGCAAATTAACACTTGGGCC
    924 GAAACAAGCAGATTTGCGGC
    925 TTAATTCCGTGATATGCGCG
    926 GGATCTAATGGTTATGACCG
    927 GCATGAAGTGGTGTCAACTC
    928 GCTTTAATGGTCGTGACGCC
    929 GCTTAGAATTTAGTGCAGGC
    930 GCGTCAGAATTTATGCCACA
    931 GCTAGATAATTTAGGCCACG
    932 GCTGATAATGCTGAGGACTA
    933 GCAGAATTGCATAGACGCAC
    934 GCATGATTAGCATAGACGGA
    935 CCAGCAATAGCAATCACGGG
    936 ATTGCACATTCAACTGACGC
    937 TGGCATTTACTTAGTGCGAC
    938 GAAGCCATATCAATGCTCAC
    939 GCGAGCAATTTCATGCCACT
    940 GGCCCAAGTTTGTGACATGA
    941 GGGCATAATGGTTGATACTC
    942 TTGGTGCATGGATCTCTCCC
    943 TTTAGGGCAGGTTAGCTTCC
    944 TTATCCGGCTAGAGTGCGTC
    945 TGATGACCTGTTAGCAGTAC
    946 GGACCATGTGCTACGCAAAT
    947 GTGAGCAGATTCAGCCAGAC
    948 GAGAGACCATGCAGCCGATA
    949 GCGTCGTCAATGTTGCCACT
    950 GGGTTAATCCCTGCCACGTA
    951 GTGCTGACATTCGCGCCATT
    952 GCCTGTAATCGTGGGCACAT
    953 AGCGCGTGAAATGCACATAC
    954 AGCGTCTGAAATGCTATCAC
    955 AGTGCGCGAAATGTTCTACA
    956 CGTCGCCAATATGATCGAAT
    957 CGCCACAAGTTCGAGCGATA
    958 GCCCTACAGCGTGAGCTATA
    959 TGTCAGTGATCCGGGACTAT
    960 GTTATCGCACCTGAGGCGTA
    961 GTTGTGACCTCTGAGCACGT
    962 GTTTCACGCTATGCGAGCCA
    963 GTTTACCGCTCTCCAGGGAT
    964 TGCGTACCTCCTGCATGGTT
    965 TGACTACCGTGTCGCATACG
    966 TGGACTACGTGTCTCGATAG
    967 TAGTGATACTGACTCATGGC
    968 CGTCTGATACAGCCCAGTGT
    969 GCCGTATCACGACGCTAGAT
    970 AGCTCGATACAACGCTAGAG
    971 ATCTACTTAACGCGCTACAG
    972 GACATCGTACCACTGCGTAG
    973 GACTCGTGACCACTCTGTAG
    974 GACTCGGACCATATCTACGG
    975 CACTACGCAAGACTATGTAC
    976 CGAGTCTCACAGCAATCTAG
    977 CGATCTAGCACGCAATATAC
    978 GACCAGCGACGACAGTAGAT
    979 CGTAGACAGCCACGCAGTTA
    980 CGTATGCTACCACCGATTAT
    981 CGTGCGATACCAGCGTAGAT
    982 CTCCGTACAGCAGGCAGTAT
    983 CTCGTCGTACAGCGATCAGT
    984 CTACAGATACGTCGAGAGAG
    985 CTACGCGACACGCATGAGAT
    986 TAGACGCTCGCACGGTAGTA
    987 GCCGCTAGACGACGGTATAT
    988 GTATCACTAGGACGAGGTAT
    989 GTACTCACAGTGCGAGAGCT
    990 CGACTACACAGCTCAGGATA
    991 CACCGACAACTCGTAGAGAG
    992 CGACCCACACTAGGAGAGAT
    993 ACGCGCACAACAGGAGACTT
    994 AGTACCACAACTCAGACGTG
    995 AGTACAGCAACGCAGAGCCT
    996 GTCAGCGACCGTCAGCTATT
    997 GTCAGGCACTAGGAGCTATC
    998 TGTCGGTCACTCCTGGACTA
    999 TCGGTTCACGTCCGCATGTA
    1000 TCGTTTACCTGTCGCGCTGA
    1001 TGTGTCTCACTTCCGCGAGT
    1002 TCTGAGCACTCTCTCGTAGG
    1003 GTTGATGACTCGCCACACGT
    1004 CTGAGATCACAGCAGACTAG
    1005 TTAGACTCCTCGCCGGTAGA
    1006 TATAGCTCCTAGCAGGCGTA
    1007 TATGCTCCACGTCTAGTGAG
    1008 CTCTATCACCAGCGATGAGA
    1009 CGCTCCAGACAGCATATAGA
    1010 ACATACCGAAAGCTCTAGCG
    1011 ACATCGCTAAAGCACATCGG
    1012 ATATCGCGCAATCAACGCTA
    1013 CGATGCGCCACTCAAGGTAT
    1014 TATGCCGACGGTCAGGCTAA
    1015 TATCGCCACGTCCGGTGATT
    1016 TCTCGCTCACTGCGTATGAT
    1017 TATCCGTCACTCCGTAGAGG
    1018 TATCGACTATCCCTGAGACG
    1019 GTATAGACCTCTCAGACGCG
    1020 CTATCGTAATATCAGTCCGC
    1021 CGATGACAATTAGGTACACG
    1022 GAGCATAATGACGTAGACCG
    1023 CGACAATACTTGACAGCACG
    1024 CGATGATAATAGAGTAGCCG
    1025 CTATGATTAAGTCGTAGCCC
    1026 AGGTGAATAACGCATACGCC
    1027 GAGTGAGTAATGCTACGTCA
    1028 GATCGACGAATGTTAGAGAC
    1029 GACTCACGAATGCGGAGACT
    1030 GACCGTCAATCGCGTCAGAT
    1031 TACCCGCATCGACGGAGTTT
    1032 GTCAGCGCACTCCTGGTTTA
    1033 TCAGGCCCACGTAGCGTTAT
    1034 TTCGCGCTATCCATGCGTGA
    1035 TGCTGATACTCGGCTGCATC
    1036 TGAGTAGCATCGGTGACTTC
    1037 TTGTATCACTGTGCTGCCCA
    1038 TTTAGTCAGTATGCTCGCGG
    1039 TTACGTTTATATGGCCGAGG
    1040 TGAGATCACGTTCGCCGAGT
    1041 GTATCATTAGCTCCGCAGAG
    1042 TATCATGTAGACTCGGAGGC
    1043 GTATGCTTAGATATGCAGCG
    1044 TTGTAGTTAGCTCTGCACGG
    1045 ATATCGTTAAGCCATACGCC
    1046 ATTCTGATAACGCTCTCGAC
    1047 ATTCGTCCAACGCGGTCGAT
    1048 ATATGCACAACGCGCAATCG
    1049 TTAGCTCTATCGCAGTCCGA
    1050 ATTAGCTGAACGCCTCGCAA
    1051 ATTATCTCAACGGAGGAGCA
    1052 ATGTTGCTAACGGACGGACA
    1053 ATGTGTTCAACGGAGACAGA
    1054 CTCTTTCTAAGTGAGTCGAG
    1055 CTGCTTGAAGTCGTCTCACG
    1056 CTGCGTTGAAGTGGCTTACT
    1057 GTGCGTTCACATGGCCGTAT
    1058 GTAGCCGCACCTGACTGTAT
    1059 GTAGCGCCACCTGACGTTAT
    1060 GGCGCGTCACATGATACATT
    1061 GGTTGCTACGATGACTCAGT
    1062 GAAGGCCCGTACACTCTATA
    1063 GACAGGGCACACGACTCTAT
    1064 TGCGCGGCACTCGTTCTATA
    1065 GCGGTTGCACTCGTAGCATA
    1066 GAGGCGTGACCAGTCCATAT
    1067 GGACGCTCACCAGTGCTTAT
    1068 AGTGTCCAACCAGACCAGAG
    1069 AGTGCCATACAAGCGCATAG
    1070 GTAGCCTTACATTGGCAGAG
    1071 GTCGCCGCACATTCGGTTAT
    1072 GTTGAGTCAGATTAGCAGTC
    1073 TCGTAGGGACTGCGCTCATA
    1074 CTCAGATGACAGCGACGCAT
    1075 CTCTGAGGACAGCCGAATCT
    1076 CTAGGATGACAGCCAGACAC
    1077 CGTGAATTACATCAGACAGC
    1078 CTGATTATAGCTCATACGCC
    1079 CTAATATGATGACAGTCCGC
    1080 TACTTATGATGACTGCGGAC
    1081 GAACTATGCTGACAGTACCG
    1082 CGATTCTGACCACATACGAG
    1083 CTAATCTGACCACGAGACGA
    1084 CTGTATTGACATCAGACGAG
    1085 CTTCTCAGACATCGGACGAG
    1086 GCACTGTGAATTAGCGAGCA
    1087 GCCTACGGAATTGGCAGACT
    1088 GACCTGGAATTAGCACACGC
    1089 GCCTGCGAATTAGCGGACAT
    1090 GCGATGCTAATGATGTGTAC
    1091 GCCCGTCTAATGAGTGGACA
    1092 GCCTAGCTCATCAGACGGAA
    1093 GCATGGACATCCTACGAGAA
    1094 CGCCTGCCAAGCTGTGATAT
    1095 GCCTGCGCCATCAGTAGATA
    1096 GCACGGCCAATTACTCGATA
    1097 GCAGCGAGACCATGTGATAC
    1098 GCAGCAGCACACTGATCGTT
    1099 GACCCAGCACATTAGCGAGA
    1100 GCTCCTGCAATGTGCGGATA
    1101 GCGCCTGAATTGTAGCACGT
    1102 GCCACAGCATTGGAGAGAAT
    1103 GCCAGGCTAATGGATAGTAA
    1104 GCCCTGCGAATGAAAGACAT
    1105 GCAGCGGGAATTAGATATAC
    1106 GCAGGTGCAATGATTCTACC
    1107 GACCGGGCAATCACTTCAGA
    1108 GCCGGGCAATGCGTTCATAT
    1109 CCCAGGGCAAGCGATCATAA
    1110 GCCACAGGCAGGGCATATTA
    1111 GCCTAATCCTGGGACACTGA
    1112 TCGTCTCGATCTAGGCCATG
    1113 GTGTCTCGACTCAGCCTATA
    1114 GACGTAGTAATCATGTCTCC
    1115 GACTTATACGTCATGCGACC
    1116 ACGATGTAACACAGCGACCG
    1117 AGTCGTGTAACCATGTGACA
    1118 GTCGTGACAGTGATGTACTC
    1119 GTGGAGTGACGTATCTCTAA
    1120 TAGAGGTGACGTAGTCCACT
    1121 GTCGTGCGAGATAGCTCTTA
    1122 GTGTAGAGATATAGCATCGC
    1123 TAGTCGTGAGATAGCGATTC
    1124 CAGTGTGTACGAATACGAAG
    1125 CGAGTGTCACATACCACATA
    1126 CGTATAGCAGACAGCGCAAT
    1127 GACATCGACGACAGGCCATA
    1128 CGAAGCTCACGTAAGTCAAG
    1129 TAGTGCTCACGTAGCCCAGT
    1130 TGCCCACGGTGAGCTAGTTT
    1131 TAGCTGCCAGGAGCGTTCTA
    1132 TCGGCCTACGCTGTGCATTA
    1133 TAGGGTACTGATGAGCACTC
    1134 CTACGGGAAGGTTAGCACCA
    1135 TGGTGATACCTGTGCGCCTA
    1136 GATTAGATACCACTGCCACA
    1137 GGAGTGATACCTCGATCCAC
    1138 AGCTGACGAAATCTTCACAC
    1139 GAGGAGATAATGGTCACTAC
    1140 CACGGAATAATACATCCTCG
    1141 ACAGCAACAAGTCGAGCCGT
    1142 ACGGAGAGAAATCAGCCCTC
    1143 CAAGAGATAATACGGCTGCC
    1144 CAAGTCCTAAGACAGCTACG
    1145 ATAAGCGCAAGACAGGCGTC
    1146 ATCTGAGCACAACTAGGACG
    1147 CACAGGCTAAGACAGGAGCT
    1148 CATAGCGTAAGCCAAGCAGC
    1149 CATAGTCTAAGCCACATCAG
    1150 GACAGTACATGCCAATCAGC
    1151 GCGGTAATCGGTGCATCAAA
    1152 GGGAGTATAGCTGACCATCA
    1153 GTAGGCAGACCTGATCCCTT
    1154 GAGCCAGACCACGCTTGATT
    1155 GGCGCATCACTAGCCAGATT
    1156 GGAGCTACATCCGCCAGTTT
    1157 GGAGTCTACCCAGGGCATTT
    1158 CGCGCTCTACACGATGGATA
    1159 CGTGCCACACCTTGGAGTAT
    1160 CGCGGCACACAGTTCAGTAT
    1161 GCTCGTCCACAGTGCGTTAT
    1162 GCTGACGCAGAGTCCAGTTA
    1163 CCGTAGCGACAATCAGCTTA
    1164 ACGCACCGAAAGTGAGCGAT
    1165 ACGTCCTCAAAGTGCAGACA
    1166 ACGCAGTCAAAGTCATATCC
    1167 CAGAGTCTAAGATCACCACG
    1168 CACTGTCTAAGATACACACG
    1169 CAGCGTACAAGCTATACAGC
    1170 CCGACGACAATGTACGACAG
    1171 GACTAGCGAATCTAATGAGC
    1172 CGTCGAGCAATATGAATGAC
    1173 CTGTCGCGCACTTCATAGGA
    1174 CCGCGACCACGATAGAGAAT
    1175 GGCACACACGTCTCGGATAA
    1176 GGCAGACGACGTTGCATACA
    1177 CGTGGGACACAGTCGATCAT
    1178 AGTGCGAGAACATCGTGTAA
    1179 GGCAGCACAGCTTGTACGAT
    1180 GACCATTGAATATGTCGAGC
    1181 GTACGCATATTTAGCCAGCA
    1182 GGCAATCTGTTCACGACCAA
    1183 GCTGACTAATTGCTAGACAG
    1184 GGTGTCTAATTGTATGCACG
    1185 GTTGACACATTGTTAGCAGC
    1186 TTAAGAGATTAGTCTGCCGC
    1187 TCACGTAATTTGTTAGCCGC
    1188 TGAGTGATAGCTCGGATCTC
    1189 ATGATGATAACTACGTGCCC
    1190 ATGCGAATAACTATGACGCC
    1191 ATGGAGATAACTATGCACCC
    1192 TCGTTGCGACCTATGCGTAG
    1193 TAGTTCGCACCTACTGCTAG
    1194 ATACGTGCAACCACTGCTAA
    1195 ATGTCGATAACCTCTGCTAC
    1196 ATCTAGTCAACCTGAGCTAC
    1197 AGTATAGCAACCTCAACTCG
    1198 AAGACACTAAACTCTGCTCG
    1199 ACGATAATAACAGCTCCTCG
    1200 ATAGATATAACTGACGCGCC
    1201 ACTGTAATAACCAAGCCTCG
    1202 ACTGATAGAACCACAGCGCG
    1203 ATGGCGACACACATACAGCG
    1204 ACGGCGAGAAATACGATGCC
    1205 GACGCGAGATCAATGTAGTA
    1206 CGAGAGTAATCAATCATCCG
    1207 CGAGCAATACATACATCTGC
    1208 CAACATAGTTACACACGCTG
    1209 CAGCTTATAGAGACACACTC
    1210 CCATAGAAGTAGACACCTCG
    1211 CTCAGAGACATGACACTCGA
    1212 ATCAGGTCAACTAATCACCG
    1213 AGCGCAGTAAATAGCTTAGC
    1214 ACTCCACGAAACATGATTGC
    1215 CTCAATATAGACACGATGCC
    1216 CGCATTAGAGACAGATCGAG
    1217 CGCACATGACATAGAGCACG
    1218 CGCACATTAGACAGAGAGGC
    1219 CTAGACTAATGCAGAGAGCG
    1220 GCGTATAGATGCAGAGATCC
    1221 TCACTAGCGTGGAATAGAGC
    1222 CAGACTGAACTCAATGTACC
    1223 CACGATGAACTAGATGTACC
    1224 CGAATGATAAGTATGACGGC
    1225 CGAGATGCAAGTATAGTACC
    1226 GGATAGCGAGATATAGACCC
    1227 GCATAGCACGATGGACGATC
    1228 CTCACAGGACATGCAATCGG
    1229 TATACATGCTTCGATCACCG
    1230 ATATCAATAACTGCGACGCC
    1231 AATACGAAAGATGCGGCCCG
    1232 ACAGATACAAATGTCGCCCG
    1233 ACGAATAGAAATGTGGCCGC
    1234 ACATTACTAAAGGTGCGACC
    1235 AGATTAGTAAATGCTGCGCC
    1236 ACTATGATAACAGCAGCCCG
    1237 ATATGAATAACTCCAGCGCC
    1238 AGACTGAAATCTACAGCCCG
    1239 GTACTGATAATTGGATCGCC
    1240 CCAGAACGGTTGCAGACACT
    1241 GCAATAGTTGGACCCAGGCT
    1242 GGAATAGGTGGACTCACTCA
    1243 GCACAAGTTTCGCGCATCGA
    1244 GCGGAATCTGTGCAGCATCT
    1245 GCGAGAATATGGTGACATCT
    1246 GCGGTCAATTAGTGGACTCC
    1247 CTCCTACAATGGTGACACTG
    1248 CTATTACAATGGTATGCCCG
    1249 AATCATACAAAGTGTGCCGC
    1250 CATGATCTAAGAGTGTAGCC
    1251 CAAGAAGTAAGATGCGTGCC
    1252 CATGTGATAAGATGTGGACC
    1253 AACTTAGCAAACTTAGCGCC
    1254 TCTTCGATATGATAGCGTCG
    1255 GACGTTAATTGATGAGACGC
    1256 GCGTGAAGTTGTTAGCACAT
    1257 GCCGATACATGCTGCACGAT
    1258 CGCCGATTAAGCTGCGACAT
    1259 CGTCATTTAAGTTAGCGCAC
    1260 CTCCATCTAAGGTGCGATAC
    1261 CGCTTATCAAGGTGCAGACC
    1262 GATGACTCAATGTGACTCAG
    1263 CGCTAGTGACAATTATGTGC
    1264 GCTAGGTGACAGTATGCTAT
    1265 GCTGTGCTACGACGTTGACA
    1266 GCTAGAGTAGACCGATGCCA
    1267 GTATATCGAGATCATAGGCG
    1268 GTCTTGGACTATACGAGCGC
    1269 TACTTGTAGATAGCGAGCGA
    1270 GTACTCTGACATGATTCGCA
    1271 TATACTGACCTTATCGGCAC
    1272 TCGTCTTGAGATATGTGGAC
    1273 TCATGTTACGGTATGCGAGA
    1274 TCATCTGCACGTATCGTCAA
    1275 GCGACTGGACAGATTGCATA
    1276 CGGGCGCGAAGTATTCACAT
    1277 GTGTGGGCACGTATTCCATA
    1278 TCCGGGCACGGTGTCATATA
    1279 TGGGCGCTACTGGCTCTTAA
    1280 TGCGCCGCCAGTCTGTTATA
    1281 TGGCCGTTAGAGTCTGCACT
    1282 ATGGGCGCAACCCTGTCATA
    1283 CAGCCCTGAAGACTGCGATA
    1284 CGCCGCTCAAGGCTATGATA
    1285 CGCTCCTGAAGGGTAGTTAA
    1286 GGCCCGACAGGTGCTATTAT
    1287 GGATAGGCAGATGCACTTAT
    1288 GGACAGACGTTGACCAGCTA
    1289 GTAGCGACATTGAGTTAGCA
    1290 GACTACGAATTGAGCATACG
    1291 CTACACTAATTGCAGCAGCA
    1292 CGTACCCGAATGCAGCAGAA
    1293 GACGCCTAATGACGCTGAAA
    1294 TAGCTTGTACTGCGACTGAC
    1295 GATACTCTAATGCCATCGAC
    1296 CGGCGTACAATGCCATAGAA
    1297 CGGATACGAAGGCTATGCAA
    1298 ACGGATCGAAAGGTATAGCC
    1299 ACGGCGCGAAAGCGTCATAA
    1300 CGTGAGGGAATACGTCATCA
    1301 CACAGTGGAAGACGCATCAC
    1302 GAGGTGACATGACGTACATC
    1303 GAGTAGCGAATGCTCAGCCA
    1304 TATAGCACAGTGTCCAGCAA
    1305 CGTATGTCAAGGGCCTGATA
    1306 CGAGACGCAAGGGATTTACA
    1307 GAGACGCAATGTGAATTACG
    1308 GATCGCACAGGAGCGTATCA
    1309 TGCCCAGAGCGTATGAGCAA
    1310 TGAGGGCGAGCTATCTATCA
    1311 TTGTGGCTAGGTATCGCTAC
    1312 TGGTTAGCAGGTATGATCCT
    1313 CTCACTGCAAGGATGGGACT
    1314 TCCTGTAGATCCCTATGCGG
    1315 TCGTTGTCAGCATATTGAGC
    1316 ATCATGTGAACCTATTGGCC
    1317 TACACTGGGACCTATGGGCA
    1318 TACCTGGGAGCATAGCTGAC
    1319 TAGCCCGCAGCATAGGGTAT
    1320 GAGCCTCAATGCTACGGAAG
    1321 GATGTTCAATGCTGGCCGAA
    1322 GACTTGTGAATATCTGTGCC
    1323 GCCGCCGAATTATTGAGCAA
    1324 TGGACTGATTGATAGGCAAC
    1325 TGGCAGATCGGTGTATTCAA
    1326 TATGCGTAATGGGTGTTCCA
    1327 TTAGGTCGATTGATAGTCGC
    1328 TCTGCTTTACTGCGTAGCCA
    1329 TTGACGAGTTTGCAGTGCTC
    1330 CTTGATTAAGTGCTGTACGC
    1331 CTCGGATCAAGGCTTACCGT
    1332 CCGGGCTCAACGCTTTGTAA
    1333 TGTCGCCCAGCTCATGTGTT
    1334 CTGGACCCACAGCTATGGAT
    1335 CACGGGCCAAGAGATATACC
    1336 CGCCCGCCAAGTGATGTATA
    1337 CGCCAGCCACATGGATAGAT
    1338 GCCCGGATACATGCGATTAG
    1339 GCTGGCCTACATCCGTATGA
    1340 AGATGGCGAAATCCGTATAG
    1341 GCAGGGACATTACGATCAGT
    1342 AGCAGGTGAAATCGTACTAC
    1343 GCAGGTCAATCTCTGTACGA
    1344 GCATTGTAAGTTCGGTCAAG
    1345 GCACTGGTAATTCAGCTACG
    1346 AGCATCATAACCCAAGCTGG
    1347 ACCAGTCCAAAGCATAGTCG
    1348 ATCATTTCAACGCAGTGACC
    1349 TCAGCCCTATCGCAGGATGT
    1350 GTCAGCACCAGCCGTGATTA
    1351 GAATTACGCACCCAGCTTGA
    1352 GAATGCGCCTACCAGCTATA
    1353 GAATGGCGACAGCGTACATA
    1354 GGATTGCCACGACTCACAAA
    1355 GCTCATTGACACTGCGCTAT
    1356 GAGCATGGACCACGGCTATA
    1357 CAAATGGACAGACAGCCTGC
    1358 CACTTTGAAGCACAATCACG
    1359 GCTGTTGCAGGACGCATCTA
    1360 TACCTGGCATGACGCGATAT
    1361 TTCGTGGACTTGCGGATCTA
    1362 TTCCTGCGATAGCGGCGTTT
    1363 TTGATCTGATAGCGGGTCTC
    1364 TTGATCGCATAGCGTCTGAC
    1365 TTCGAGGCATGTGGATCTCC
    1366 TTCAGCGGCTAGGCGATTTC
    1367 TCCAGCAGATCGGCGAGTTT
    1368 TTCAGCCGATCTGCCGATAT
    1369 TTCTATCGCATGTCAGCCGT
    1370 TGTAATGCCTGCCAGCCGTA
    1371 TAATTGCCTGCACAACTGGA
    1372 TAATTCCATTGACGGCAGCG
    1373 TTATTGCCATAGCGCGACGC
    1374 ACAATTTCAAAGCCTGACCG
    1375 ACAGGCCCAAAGCACTAGGT
    1376 CGAATGCCAAGGCCAGCTAA
    1377 GATGGTTCAATGCCTGGACA
    1378 CTGGGCCAAGTTCTGAGACA
    1379 CGTGGGCAATACAGTTGAAT
    1380 GAGCTGCGAATCGGTATTAA
    1381 GACCGGCGAATCGAGCATAA
    1382 GACTTCGCAATCGGCACGTA
    1383 GACGCGCCAATCGTGCTATA
    1384 GATCGCTGAATCGTGCGTAA
    1385 GATCACTGAATGCGACGTAA
    1386 GATCGTGCAATGAGGTTACA
    1387 GAGGACTAATTGAGATGCAC
    1388 GACCGATAATTCGATATGCC
    1389 TAGCATTGATCCCATGTCAC
    1390 TTCAGCTTATGCCAGTCGCG
    1391 TGACGGCCTTGCATATCCGA
    1392 GAACGCGCCTTACATCAAGA
    1393 GAATACCAGTTACACTCCAG
    1394 CAAGAACTGTTACACATCGC
    1395 GACGAGAATGGACTACACGT
    1396 TACAGACGCTTGCATAGATC
    1397 TAACGACCTTAGCGACGGGT
    1398 TAACGACGCTTTCCCAAGGA
    1399 TTACCGCTGTTGAGCCCGTA
    1400 TTCCATGTATCGAGCGTCAG
    1401 TATACGCCCTTCAGATCGGG
    1402 CTAAGCCTATGCAATATCGC
    1403 CCAGCTATAAGCATATTGCC
    1404 TACAGCATTGTCATGGACTC
    1405 TAAGCTATTGGACATTGGGC
    1406 TTAGCATCCTGTCATAGGGC
    1407 TCTAGCAGCTTTCATAGCCA
    1408 TCATCACGCTTTCCGAGGAT
    1409 GCATACATTGGACGAGAGCT
    1410 TCTAGCATTTAGCATGGTGC
    1411 TTATGACTTGATCTGAGGCG
    1412 TGTTCGCACTGGCTTAGCTC
    1413 GAGTTGAATGCAGATAGCTC
    1414 TGCAGGCTCGCAGATGCTAT
    1415 TGCGAGGACTGTAGCTTAAT
    1416 TGGGCACTCTCGCCTAGTTT
    1417 TGAAGCGCCTCGACTAGGTT
    1418 TCATCGGCACTGATAGCTCA
    1419 TCATCAGGCATGGAGCCAGT
    1420 TAATCAGCGTTACGTCCGCA
    1421 GAATGTGACGCAAGTCTGAC
    1422 AGATTTGCACAGATAACGCG
    1423 GATTACTGACCAGCATCGAG
    1424 AACTATCGAAACCGCCAGGG
    1425 ATAATACAAGAGTCGCGCCG
    1426 ATAATCATAACCTCGACGCG
    1427 ATTATCATACAAGGCAGGCG
    1428 TATATCGGATCAGCAGGTCA
    1429 TAATTTCGCTACGCAGGGAG
    1430 TAATCCTGTTACGCGGAGGC
    1431 CTTTAGCTCCACGCAGTGTG
    1432 TTCTAGCCGTCCGCAGTTTG
    1433 GTCATGCGAGCAGCAGTCTT
    1434 GGCGTTCGAGCAGTCATCTT
    1435 TACCGCCAGTCAGCGAGTTA
    1436 TACCGCCTAGCAGCATTGGT
    1437 TACCGCACTGCATGTCAGGT
    1438 TGTCTCGATGCAGGTCTAGT
    1439 GCCGCATGACGAGGATATAC
    1440 TACCGCGAGGCAGGATTCTT
    1441 TACAGCAGTGCAGGGCCTTA
    1442 GCAGCTAGAGCAGAGTATCA
    1443 GACAGCAGATCAGAGACTCC
    1444 TAAGCACGTTTAGAGCTGAC
    1445 TAACCGTGTGCAGATCGGAT
    1446 TACTGCGGACCTGGATCTAC
    1447 TCAGGGCTACTCGATTGGAA
    1448 TCCGCAGACTTAGCGTTACG
    1449 TGAGCAGCCTACGTTACTAG
    1450 TGCGTCAGATGCGTATATGC
    1451 TCGTCCAGATGCGGAGTTCA
    1452 TCGGCTATATGCCAGATCCT
    1453 AAGGACAAAGAGCGCGTCTC
    1454 TAGCACCGATGGCGAGCTTA
    1455 TGTCCACGGTGCCGCAATAT
    1456 TGGTCCGACTGCTGCTACTA
    1457 TGTGCCGACTGCCGTCTTAT
    1458 TTCGCAGTATGGATCGGTAT
    1459 TTACGCAGTTGCATGGAGCT
    1460 TTCTGATTAGCTGCGGACGC
    1461 TGGTTATACTTTGCGAGAGC
    1462 TTTGTTAGCTTCGGGCAGCC
    1463 TTGGTCTGATCCGGGCATAC
    1464 TGCTTGGACTCCGGCGATTA
    1465 CTGCTTGGACCAGCCAGTTA
    1466 AAGCTGGGAAACGCACACCT
    1467 AAGCGGGCAAACGATATGCT
    1468 AAATGCCGAAACCATCTCGT
    1469 CCATTCGGAAGCGACTCGAT
    1470 TACATGGGCTGAGAACGCAA
    1471 TATTGGGCACGAGCGCCTAT
    1472 CATCCGGGAAGAGTAGCACA
    1473 ATTTCATGCACATAGCACGC
    1474 ATTGCAGCACAAGCCAGACT
    1475 TTGCTAGGCTCAGTCCCGAT
    1476 TTGGCGAGCTGCGTTCTCAT
    1477 TCCCAGAGATGCGACTGCTA
    1478 TTCGCTGGATCGGCATGTCT
    1479 TTGCTCCTAGCTCGCGTGAT
    1480 TTGCTGCTAGTCCAGTAGGC
    1481 CATTAAGCAGTCGAGAGACC
    1482 CGTTAATGCAGCGAGAATCA
    1483 CGCAAGCTCAGCAGAATTAC
    1484 CCATGTCGAAGCATTCATAC
    1485 CTGAATGTAATCATCGTGCC
    1486 CTTAGATGAATCACTGCCAC
    1487 CTTCACGGAATCTAGGCACA
    1488 CACTCTTGAAGCTAAGCACA
    1489 CCTCTAAGCATGTTGACACA
    1490 CATGCCGGAAGATGCGTACA
    1491 CAGGCAGCAAGATGTACGAC
    1492 CAGTGGGCAAGATAAGATTC
    1493 CCGTGCCCAAGCTAGTGATA
    1494 GATCGGGCAATCTGCGTACT
    1495 TTCAGTGCATTATAGTGCGG
    1496 TTATCTGCATGAGTAGGTCG
    1497 TCGATAATCTTTGTAGCGCG
    1498 TCTTACAGCTTTGCAGGGAG
    1499 TCCTACATTTGCCACGGGAG
    1500 TCTTCATCAGTGAGGCGCGA
    1501 TTTCTAGGATGTATGCGAGC
    1502 TATCCAGCATTACTGCGAGA
    1503 TTATTCTCAGCACGCACGGA
    1504 TGATTCGCACTCGCGGCTAA
    1505 TTTGTATGAGTCGCTCCGAA
    1506 TTCCGATCAGTCGATGCAAA
    1507 GATCGTCAATCTGATGCACC
    1508 AGATCGCTAAATGAGGACCC
    1509 GATGCTATAATCGTATGGCC
    1510 AGGAGCGTAAATTATCAGCC
    1511 GGGCGATGACTATATCTGAA
    1512 CTGGATTGACACTAGCATAC
    1513 CTGCGGATACCATAGACAAC
    1514 ACTGCAATAACATATCCGCG
    1515 AATGACATAAAGTGCTGCCC
    1516 ACATGCAGAAAGTAGTCCGC
    1517 ACAGGCGAACAATGTACCCG
    1518 ACCAGCACAAAGTCTACTGT
    1519 AGAGAGCCAAATGACTGTCC
    1520 TAGTGCATAATTGCTTGCCC
    1521 TGAGCATATAGTATTCGGGC
    1522 TGAGCGTTAGAGCTTGATCC
    1523 TAGGCGCTAGGACTCGTTAT
    1524 TATGGCCGACGATGTGTCAC
    1525 TATGGCTGACGTAGCGCACT
    1526 TCTCGGTTACTGAGTGGACT
    1527 ATAACGGGACAGAAGCTGCT
    1528 ATAGAACTCAATAGCCGCTC
    1529 CATAATACACATACGCTGCG
    1530 CAGTACGCAAGCAGATAGCC
    1531 CAGACGCGAAGATAAGTTCC
    1532 CAGCCAAGATAGCATACTCG
    1533 TCCCATAGATAGCTCGCTGG
    1534 TTCGCATGAGTGCTGAGTAC
    1535 TTCCATATACTGGTCGGCAG
    1536 TTTATGATATGCGTCGCGGA
    1537 TTTCTTATATGCGCGAGCGG
    1538 TGTTGCATATTAGCGGCTCG
    1539 TATATGACATCTCTTGCCCG
    1540 TTGTCACATTTGCGCTCCGA
    1541 GCATCCGAATTGCGACGACT
    1542 GGATCTGAATTGCGCGACCA
    1543 GGCTATGAATTTCGCATCAC
    1544 GGATATGCAATTTGTAGCCC
    1545 CAGCGTATAGCAAGATGGAT
    1546 CGAGCGATAATCAAGTCGAG
    1547 CGCGGATGACACATACTCAG
    1548 CGACGAGCACCAATTCGAGA
    1549 CCGTAGTGACCAATGCAGAC
    1550 GCGATATACATCATTCGGAC
    1551 GACAGTCTAATCACTCGTAC
    1552 GCAGTTATACTAAGGTGTGC
    1553 GCAGTAGTAATGAGTGTCAC
    1554 GCAATGTAGTCGAAGTGTCT
    1555 GCATATAGATACCATTCGCG
    1556 CGAATACTAGACACATTGCG
    1557 CAACTACAGTACACAGCGTG
    1558 AGACACAGAACTACCGCGTG
    1559 ATAGCACAACGTAGACGCCG
    1560 ATACAGTCAACTACATCGCG
    1561 AGTACAACCTAGAATCCGGC
    1562 GAAGACTACTAGATACGCGC
    1563 CGATAATACTACAGACTCCG
    1564 CCGTGCGTACACATAGATCA
    1565 CGTGAGCGACACATGATCCT
    1566 CTGTAGTGACATATAGAGCG
    1567 ATGTCGTCACACAGAATACG
    1568 ATGCTACGAACTACCAATCG
    1569 ATGATAACGTACACACCTGC
    1570 TCGGTCTACGTCTGCTCAGT
    1571 GGCTCACGATCCACTGGTTA
    1572 TGCCTGATACCTTGGATGAC
    1573 GGCCGTGAATTATCATAGAC
    1574 GGCTTGGACGCATTGATAAC
    1575 CCCATCGAAGCATGTGTAAA
    1576 CGGCATCGAAGGCGTTCATA
    1577 GCCAGTTGACCACTTCTGAG
    1578 TCGCATTAGCCATGTGGAGC
    1579 GCAATCTAGTCTAATGGCGC
    1580 CTAAGATGTTCTAATCGCCC
    1581 CCAATAGTAAGTAATGGGCC
    1582 TCATTATACTCTGATGGCCC
    1583 ATGCTAATAACTGATCGCCC
    1584 AGTGTCAACCATGATGAACC
    1585 AGAGCATAACATCATGGCCC
    1586 AGAATCTAACAGCGATGCCG
    1587 ATTTAGACAAGTCGATGGCC
    1588 ATATTAAGAAGTAGGCGGCC
    1589 CATATCAGAATACGATGGCC
    1590 GATATACAGGATTATGGCGC
    1591 CATAAATTGGTTCACACCGC
    1592 GAAACTCCAATTCAGCGGAC
    1593 GAACAATGAATTTAGCGGCC
    1594 TTCCATTAGATGTGATGCCC
    1595 TATCATATCATCTGAGGCCC
    1596 ATCAGAAGAACTGCACGTCC
    1597 AGCACAAGAACTACGCGCTG
    1598 AGCAAAGAACCATGCCGCGT
    1599 TAAAGAGCAATGTGGCGTAC
    1600 TTCAGGGCATTGAGCGTAAA
    1601 TTAATGGGCTTGAGCGTATC
    1602 TTAATGCGGTTGAGATCGAC
    1603 GCAGGGATAGCAGATACATC
    1604 TCAGGAGAGGCATCGCATCA
    1605 TTATCTTAGGGATGCGGATC
    1606 TGTGCTCTAGGTCATCCGAG
    1607 TTGTATCTAGTGCGAGGCAA
    1608 TATTATCTAGTATGCGCGGC
    1609 TAGTTATCAGAGTGACTGCG
    1610 GTTAGATCATAGTCACCGCG
    1611 GTTAGTATAGATTGGCCGAC
    1612 GTGTTTATACGTTGAGCACG
    1613 TTATCTGTAGTCATCGAGGC
    1614 TGATACTGAGTTAGCGAGCT
    1615 GTGATCTCAGAGCGCAGCTT
    1616 CAGATGTCAAGACGCGGACT
    1617 CTGGTCAGACAGCGGAATCT
    1618 CGTGGCAGACAGCTAGATAT
    1619 GTGCCGAGACTCCACTGTTA
    1620 GCGGACAGCTCTCCTAGTAT
    1621 ATGCACAACTATCAAGCCTG
    1622 GTGCTTTACTAGCGGAGCCA
    1623 TAAATATCGTATAGGCGGCG
    1624 TAATTCTACTATACGCGGGC
    1625 TAAATCGTATGTAGCAGCGC
    1626 TCCTTCACTGTAGGCTAGGC
    1627 TCAGTTATATGAGCCGACTC
    1628 TCACGTATATTGACTCCGAC
    1629 TCACCGTATTCGAGGCGACA
    1630 TCGTACTGATTGACGGTGAT
    1631 TCACAGCGGTCGAGGTTACT
    1632 TTCACGCGGTCGCAGTATCT
    1633 TACTTGACGTGACTGCATCG
    1634 CGTCACAGAGGACAGCATAC
    1635 TCACTAGAGCGTCGAGCTGT
    1636 TCTACAGTGTGTCAGAGTGA
    1637 CTACCTAATCGACAGCAGAG
    1638 CACCGATAACTACAGCAGGG
    1639 CAACGTCTAGGACAAGGCAG
    1640 CACTAGCTCAGACAGACGAG
    1641 GACTTTACAGTACGATCAGC
    1642 GACACTGACTGACATCGAGA
    1643 GAGACAGTCGAGCGATCAAT
    1644 GCACTTGTACGTCCAGTCAG
    1645 GTACACGGACTGCCAGCATA
    1646 GTAATACGCTATCAGCAGAC
    1647 CTAGATAGACATCACTCACG
    1648 TAGACTCTCGATCAGCCGTA
    1649 GACTTGCACGTACAGCCGAA
    1650 CTTATGCGACACTAGCTCGA
    1651 CTGATGCTACACTAGGCACA
    1652 GCAGACGCACTATCATATAC
    1653 GCAGTAGACACTTCTCACGA
    1654 GCAGGTACACTGACCGACTA
    1655 GCACATCACTGCACGATAGA
    1656 GCAATGACTTCGACTCCAGA
    1657 GACAAGTCATTTACAGGCGA
    1658 GTAACTTGTTTGACAGTGCG
    1659 GACACTGCATGGACAGCGTA
    1660 GCAAGGACTGAGACATGCTT
    1661 TGCGAGGTAGGTTATATCTC
    1662 TGCGGAGAGTGATATACTTC
    1663 GGCGTGAGAGCATTATATCT
    1664 GTGCTGCGAGAGTATTATCT
    1665 CCGCGTGTACCATATAATAC
    1666 GAGCGTGGACGATATACACT
    1667 GGCCGTGTACGATTATGACT
    1668 GTAGCTTGACGATGCTGACT
    1669 GTGCTGGTACTAGCTGCTCT
    1670 TAATGTGACGTAGCCGACTC
    1671 TACCGAGTGCGAGATGCTCA
    1672 TACCGATGTCGATAGATCCA
    1673 TCTCGTATAGGATGAGCAAC
    1674 TCGTGAGTAGGATGCTTTCA
    1675 TACGTGAGATGATGATCGCT
    1676 TAGTCGGTAGCATGAGTCTA
    1677 TAGTTCGAGGAGTAGTCATC
    1678 TAGGTACAGTGCTGGATACT
    1679 CTGCGTCAAGTGTGTAGAAT
    1680 TGTGCGCTAGAGTCTGTCCT
    1681 GGTGCGTCACGATCTCCTAT
    1682 GTGTGGGTACTATGCCATCA
    1683 GCTGATGTACTATCCATACC
    1684 GCTAGATGACGATCAGGTAC
    1685 GCATCTGTACGATCTCAGCA
    1686 GCATCACGACGATTATCAGA
    1687 GCTACGTTACCATGTGCAGA
    1688 GCGTAGTTACCATGCTCACA
    1689 GCGTGAGCACACTCTATCAG
    1690 GCGTGCGAATTATGTATCAG
    1691 TGTGGACACTTCTTATAGGC
    1692 GCGTGAGTAATTTGACTACG
    1693 AGGTGCGTACAAATGCTATG
    1694 CGCAGCCGAAGTACGCTATA
    1695 CGACTGCTAAGGAGCGTACA
    1696 CGATGTTGACAGACCGCACT
    1697 CATGTAGAACTGACTCACAC
    1698 CGAGCGGTAAGGATCTCACA
    1699 ACACGCTGAAAGAGTACGCC
    1700 GATCTGACAGGTAGCGATAC
    1701 TCTCGTGCAGGTAGCTGTCA
    1702 GCTCGGACAGATCGGTATCA
    1703 GCCGGTATAGCTCGATATGC
    1704 GCTGATACAGTTCGATAGAC
    1705 CCTGACTAAGCTCGATAGAG
    1706 GCTGATTACGATCTAGTAGC
    1707 GAATGCTCACGACGAGTAGC
    1708 GAACTGTCCTGACGAATGAG
    1709 TTACTGTCTATGCGATCCGA
    1710 GTTATGTCATCGCAGATTCC
    1711 AGCTATATCAAGCAAGCGTC
    1712 GCTTATACAGTGCAGTAGAG
    1713 TTAAGTAGGTAGCTGGCCTC
    1714 CAAGAGTAACTGCAAGGCCC
    1715 CACTAAGACATGCACAGCGG
    1716 CCTAGTGCAGACCACATGAT
    1717 TCATGCACGTCGCCATAGGT
    1718 TCTATACGCTCGTGCAAGGA
    1719 TCAAGCCCGAGCCGAGTTTA
    1720 TCAGCGCCAGCATTCATGGT
    1721 CCATGCGGACCAAGTCGATA
    1722 GAATGCCGAGCAATGATCCT
    1723 GAATCGGCAGCAATACTGTC
    1724 GAAGCCCAGCTAAGTGGTAT
    1725 AACAGCCCAAACCGGATGGT
    1726 TAAGCACCTTGCAGGATAGA
    1727 TCAGCCCGATCCAGGGTATT
    1728 TATGCGCCCAGGAGGCTTTA
    1729 TGCCCAGCAGGTCGGATTAT
    1730 TAGCTCGCATCACTGACGGA
    1731 GGTCCCATACGAGTGGCATA
    1732 ACTAACCCAACAGCGGAGGT
    1733 CAGCTCTAAGCAGCACAGGA
    1734 CAGGTCAAGCACATACCAGT
    1735 CTGTGCAATCACGCCAGAGA
    1736 CGGCGCAATAATGTCACAGA
    1737 CGGGACATAATTGACACAGT
    1738 AGGGCCAGACAATACACCGT
    1739 GAGGTCACAATTTGCTACAC
    1740 CAGGCACAAGATTGAGCACG
    1741 ACAAGCGCAAATACTGCCGG
    1742 ACAATCTGAAATAGCGCGGC
    1743 ATCGACCCAAGAATAGCTCG
    1744 ATAAGCACAAGCAGCGCGGT
    1745 AACACTCCAAACCGAGGGTG
    1746 AATCTATCAAAGCGACGGCC
    1747 ATTCCCATAACGCGGAGGAC
    1748 ATGCCAGCAACGCGCTAGAA
    1749 ATGCTCACAAGCCACGAGAG
    1750 ATGCTCCAACGATACATACG
    1751 CAGCTTCAAGAGTACATACG
    1752 CATGTCACAAGGGCATAGAC
    1753 CATGGTCTAAGCCCTACAGA
    1754 ACATGGCGAAAGCACCACGT
    1755 CTTAGTTCAATGCACGCACG
    1756 CGCCAGTTAATGCACGACAG
    1757 CAGCAGCAACTCGACTAGAG
    1758 CCGAAGTCAACTGCGCTAGA
    1759 CCAGTGTCAATAAGAGACGT
    1760 CCAGGCGAACTGATCGTAAA
    1761 CCTGGTACAATCAGTAGCAA
    1762 CTAGTGGCAATCATCAGACA
    1763 CAATGCGAACTCACTAGACG
    1764 CATGGCGTACCAATACCTAG
    1765 AAGTGGCCCAAATAACTGCC
    1766 CAAGGCCCAATACACAGGGT
    1767 GATCTGCCAATGCCGCGATA
    1768 GATTCGCCAATGTGCGCTAA
    1769 GAGCCGCCAATGTCACTAGA
    1770 GCGCCCGGAATGTCGTATAT
    1771 GCCGCGCCAATGTTACGTTA
    1772 CTTCGCCCAATGCGTAGGAA
    1773 TTCCCATGATCGCTGACGAG
    1774 TTGCGGGAGCTGCCTCTTAA
    1775 TTTCCCGGATAGCCGCTGTA
    1776 TTTGCTGGAGTATGCGCTCA
    1777 TTGTTCTCAGCTTGCGGCAG
    1778 TGTGTGGCAGCTTAGTTCAC
    1779 TCTTGGGTAGCATCTGTCAC
    1780 TGGGTGTCAGCATCTACGCA
    1781 TTGTGGCAGGTATGCTCCAA
    1782 GTTGGGCACGGATCTCTATA
    1783 GCCGAGGCACCATGCTTATA
    1784 CGCTTGGGACAATCGCGTAT
    1785 CCGCAGGGAACTTCAGCATA
    1786 TGGAGGGCAGTCTCTCATAA
    1787 CTGGGTGCAAGTTGTATCAA
    1788 TGGCGCACATGGTGTCATAA
    1789 TGGCATCACTGCTGCGGAAT
    1790 TGCCAGTCATCCTAGCGTGT
    1791 TCAGGCCAGGACTGCTTATC
    1792 TTGGCATAGGAGTGCTTCTA
    1793 TTTGCAGACGGTGTGCTATA
    1794 TTGAGTCAGGGTGCCCAACT
    1795 TTTAATATCGTTGCCCGAGC
    1796 TCAGGATGATGAGCATGTAC
    1797 CTCAAGCTGGGAGAACAGTA
    1798 TCAGAAGTGGCTGGATCATA
    1799 TCTCACATGGCTGGAGCATT
    1800 CTACTGACACTGACCAGGGA
    1801 TCGTAGCGACTCTCCAGGTT
    1802 TACGTGTCACTATCGTCGAG
    1803 TATAGTTACGTCTCGCACGC
    1804 TACCGTTACGTCGCTCAGAG
    1805 CACTACAACGTGCTACAGAG
    1806 ATAGGTATAACGCAGTACGC
    1807 ATAGCAGTAACGCATAGTCC
    1808 ATAATCGTAACGCACCGACG
    1809 ATGAGTGTAACGCCTCGACA
    1810 ATGTAGCGAACGTACTCACA
    1811 ATCTAGCGAACGGAACTATC
    1812 GTAGAGTCACGATGCAGTAC
    1813 GTAGTATGACGTAGCAGTAC
    1814 GTACGTCGAGCTAGATCGCT
    1815 GAGTCTGTACGAGGTATCAT
    1816 CGTGTCTTACAGCACTACAT
    1817 CGTGCGCTACAGCAGTCATT
    1818 GTAGCCTAGACGCAGTCGTA
    1819 CGTCTCGCAAGTCGCGTATA
    1820 AGTCGCGCACAGCAACGTAT
    1821 ATCGAGGTAACGCCATATAC
    1822 CTCGTGACATAGCCATAGAT
    1823 ATGCGACGAACGCGGATATA
    1824 CTAGACAGACTGCGACATAC
    1825 TAGTCGTAGAGGCGCTATCA
    1826 CTATCGAAGTCGCGTGAAAC
    1827 CTGCGTATAGAGATCAATCC
    1828 CCGCGTATAGACAGATATGA
    1829 CTCGCTTACGACAGACTGGA
    1830 CGCGGAGGAGACATAGCTTA
    1831 AGCGTCACACACAAGACTGG
    1832 CCTACGAGACACATGACAGG
    1833 CGCCGAGTACACATGCAGAT
    1834 CCGTCGATACAGACTCAGAT
    1835 CTCGTCAGACAGAGCGGATT
    1836 GTCTCGCCACGTATCGGATT
    1837 TCTCGCGTACTTAGGCATCA
    1838 GTCTCGGTACGATGTAGCAA
    1839 CGTGTGAGACAGTAGCATAT
    1840 CGTGTAGCACAGCGACGATT
    1841 GTGTAGCTCAGTCAGCATCA
    1842 AGGTAGATAACGCTAGATCC
    1843 CTGTAGAGACATCTGAATCC
    1844 CTGATACGAAGTCTTATGCC
    1845 CACGCTCGAAGACTAATGAC
    1846 CACGCGATAAGACGTATAGC
    1847 CTAGCAGTAAGTCTATGCAC
    1848 CGTAGTTGAAGTCATCGACA
    1849 CGCGATAGAAGTCAGGACAT
    1850 GACGGACGACATCTGAGCAT
    1851 CATAGACGAATACAGCGGGC
    1852 GATCACGACCTACTAGCAGG
    1853 AGATATAACGAACTCTCGCG
    1854 GATTATAGACTACTGAGGCC
    1855 GAGTTTATACTACAGTGCCG
    1856 GTCACTTACGCTCAGGCAGA
    1857 TCGCTAGACGCTCTGGCATA
    1858 GTACGCTCAGCACTGGCATT
    1859 GACGCGCTAATACTGTCACA
    1860 GCGTGCATACGACTGCCATA
    1861 TGTAGTCTAGTGCATGGTCA
    1862 GTATAGTCAGAGCTGGCACC
    1863 CGTCAGTCAAGTATGGCACA
    1864 ACGAGAGTAAATATGCTGCC
    1865 ATAGAGCGAACGATAGTTGC
    1866 ATCTGACTAACGATGATGCC
    1867 GTTGTAGGACGTATGATCTC
    1868 TTAGTCGAGTCTATGAGCCC
    1869 CGACGATACAGTAATCTAGC
    1870 CTGATACAGGCATAGACATC
    1871 GGTATCAGAGCTAGGACTAT
    1872 TCTATCTCAGCTACGGTCGA
    1873 TCAGTTCGATCTACGGCTAG
    1874 TCAGTGCGACTCAGGTACGA
    1875 GTCACTGCACTCACGGTAGA
    1876 TAACGAGTCTTCAGCACGTA
    1877 GAAGTCGCCTACATAGCCTA
    1878 GAAGTCCGTTACATGACCAT
    1879 GTCAGAGGATCGAGCCACTT
    1880 GCGAGACAGGTCAGTACAAT
    1881 CGTCAGAAGGCTCGCACATA
    1882 GCATACAGGTTACGACGCCT
    1883 GCGATACAGGTTCAGAGATA
    1884 GGACGCATAGCTCGCAGTAT
    1885 GGACGCAGATCGCAGCATAT
    1886 CGGCGTTAATCGCAGAGAAC
    1887 CGCGTTCTAAGGCACGGATA
    1888 CGCGTCGCAAGGCTGTTATA
    1889 CGATACGCAAGGCTACGACA
    1890 CATCTAAGGACACTACACTG
    1891 TATCATCGAGGACTCAGTGC
    1892 CACCGAGCAAGACTGACATG
    1893 CGCACCCGAAGTCAGAGATA
    1894 CGGCTAGGAAGTCAGCATAA
    1895 ATGCTGCGAACGCGCCATAA
    1896 CCGCGTGCAACGTGTTCATA
    1897 GTCGCTGCATAGCATCTCAG
    1898 GTCTGTGCATAGAGCGTCAT
    1899 GTGGTGTCACTGATACGTCA
    1900 GGTTAGCACTAGATCGCACT
    1901 CGGGATCTACAGCATCATAG
    1902 CTGGATATACAGCACTCACA
    1903 ATGCGGCTAACGCCTCATAA
    1904 TCGCGGCGCACTCTGTTATA
    1905 TCGTGCTACTGCCACTGTAT
    1906 TAGGACACTTCGCCACTATG
    1907 TATGACAGTTCGCGCTACCG
    1908 TCGCGCAGTTAGCCCTATGT
    1909 TAGCCACCGTAGCTGATCGT
    1910 GTAACCCGCTATCAGATCGA
    1911 AGAGCGCAACACCACATTGT
    1912 AGGCTAAGAACGCACACTCG
    1913 GAGCCTAGACAGCTTCATAC
    1914 GGCAGTTCACGACTCGACAT
    1915 GGCCTTAGACGACTCGCATA
    1916 GGTCGATCAGCACTGCATAC
    1917 GGAGAGTCAGCACAGTCCTA
    1918 GTATAGGCAGCACGGCTCAT
    1919 GCACGGCGAGCACTATCTTA
    1920 TAACGTCCTGCACGATCTGT
    1921 GGACGCCTAGCACATCTGAT
    1922 CGCTGCACATCACATGGATT
    1923 GCACATCGAGCACATGCAGT
    1924 GCACGACCAGCTCTTAGGAT
    1925 CCCACCAGACAGATAGAGGT
    1926 CCCGACGCACGAATAGATAG
    1927 CCCACGACAGATACATGAGT
    1928 CTTCGCGCAGCTACATAGAT
    1929 CGCTCCGAAGCTGCGATAAT
    1930 CGCCGCGTAAGCAACAAATT
    1931 CGACGCTCAAGGACTCATAA
    1932 CGCACACTAAGGATCATTAC
    1933 AGACACGCAAGAAGCTGGCT
    1934 GCACGCATAGCAGAGGATCT
    1935 GCTACGTCACTGAGCAGGAT
    1936 GTACATCTCGTGAGCAGAGC
    1937 CTACACGACTTGAGACGAAG
    1938 CTAAGTACGTGCAAGCAAGG
    1939 GACACGTAGGACAGCTATGC
    1940 GACATAGTAGACATCTCACG
    1941 GACAGCGTAGACATCGTCAG
    1942 GACTATCACGACATTCAGCG
    1943 GATCTACACGCTACCAGTGG
    1944 GCTTACTACGGATAGATCAG
    1945 GCGTATCTAATGGAGTAGCA
    1946 GCGTATTTACAGTGAGCGAC
    1947 GCGTATATCGAATTGAGTGC
    1948 GCGTTCACAGAGTCCACGAT
    1949 CGCGTATCAAGGTCACGACA
    1950 GCTATTACAGTGTCAGAGAC
    1951 CGTCAGATAAGGTGAGTTAC
    1952 CGTCTGTGAAGGTCAGCTAA
    1953 TATTAGCACTCGTCAGCAGC
    1954 ATGTTATCAACGTCAGCGAC
    1955 GGCATACTAGAGTCAGCGAT
    1956 AGTGCGATACAATACGAGCG
    1957 CAGCACACAGAGTACAGCGT
    1958 CGTAGCATAAGGTCAGCACC
    1959 GTCCATAGACGTTGATACCA
    1960 GCTACGATAGATGAGCCACG
    1961 CGGAGTACACCAGATCCAGA
    1962 GAGCGTATAGGAGATCCAAC
    1963 GACTGTAGAGAGACGATCCA
    1964 CTAGTAGGAAGTGCGATCAA
    1965 CGTAGAGGAAGTGATACTCA
    1966 CGTATCGGAAGTGAGTATCA
    1967 CTATGACGAAGTGAGAGTAC
    1968 GTTCGTAGAGATGATCGTCA
    1969 GTTCTCAGATAGTATGCAGC
    1970 AGTCTGTTAAGATATGCGCC
    1971 AGCACGGAACAGTAAGCCCT
    1972 ATCCAGAGAACGTGAGATCC
    1973 GACAGTGTAATATGAGGACC
    1974 CATAGTAGAAGATTCGAGCC
    1975 TGAGATATAGTATGCGGCCA
    1976 ATGAACATACTATACCGCGC
    1977 TTCTCTATATCGTGCGCGGA
    1978 TGAGTTTACGTGTATGGCAC
    1979 ACGGCATCAAAGTTGCATAC
    1980 ACGGGCTCAAAGTATGATAG
    1981 AGGCGCTTAAATGTGGATAC
    1982 CTGCCGTTAATGGCGGACAT
    1983 CTGAGCCAATAGGCGCACTT
    1984 TAGGCATGATGAGAGCTATC
    1985 TGCCTATGAGGAGTATGAAC
    1986 GGGCTATAATGAGCTTGACT
    1987 TAGGCTTCATCAGCTATCAG
    1988 ATTGCTTCAACGGGCATTAC
    1989 TATGATCCATGCGACTCGGA
    1990 TTGTATCCATCGGCCCAGTG
    1991 ATCAAGGCAACCGCCAGTAG
    1992 TCTCAGCCATCCGTGATAGG
    1993 TATCAGGCATCCGAGCATAG
    1994 TTAAGCTCCTCAGTCCATGT
    1995 TAAGGGCGATGAGCCTATCT
    1996 TAAGGCCGAGGAGCTTTCAT
    1997 TAAGGCAGTGGAGCCCTCTA
    1998 TGGACAGGCTGCGCTCTATA
    1999 CTGGAAGCCTGCGACCAAAT
    2000 TCAATGCACTGAGCCCGAGA
    2001 GATTCACACTGACCCATGTA
    2002 TAAATAGATTGGAGACGCGC
    2003 GCATTAGAAGGTCTGGACTA
    2004 ATTGGCATAACGTATTGCGC
    2005 CAGGACTGAAGATCGAGTAC
    2006 TAGAGTCAGTCATAGCTCGA
    2007 TTTATCGTAGCTGGCTGCCC
    2008 AGGATTAGAACCTACGCACC
    2009 GCCGTGAGACCACTGTACTA
    2010 GACGCTGAATCCTATTGACA
    2011 CGCCTAAGGATCGTGAAGTA
    2012 CGACGACGAAGCTGCATGAA
    2013 ACTCGAATAACAGCATCTCG
    2014 CCCGTAAGCATGGCACAGAT
    2015 CAATACAAGATTACGGCCTC
    2016 GATCAGAATCTATGGTACGC
    2017 TCTGTGTACTGCTCGCCAAT
    2018 ATATTTGGAACGCAGCTCAC
    2019 TGCAGTATCGCAGCGGTTCTA
    2020 GGGCAATGTTTATCCACAGA
    2021 CTGACCGAATCCAGCAGAGA
    2022 GATCGTGAATCCGCGCACTA
    2023 GAGCCGTAATCCGAGCGATA
    2024 TACTCCTGACGACTTAGGCA
    2025 TGCTGTCACTCGGCGTCTAT
    2026 GTACTAGCATATCATCGACG
    2027 TATCGCATAGATCAGTGAGC
    2028 TACGGGCAGCCAGGTACTTT
    2029 GTTCATCACGAGTGCGTAGA
    2030 CATGTATCAAGATGGCTGAC
    2031 GGTCGCGCATTCCAGCATA
    2032 GCACATATCTAGCGACATCT
    2033 ACGCGGCTAAAGGTAGATAC
    2034 CACTGCCCACAAGATGTAGA
    2035 GGATTTACATGGCCTAGCAA
    2036 CATGACACAGAATCGACCGT
    2037 AGAGGCATAAATGAGTCTCC
    2038 TGAGTAGTACGTTACGCCTG
    2039 CGATAGCGAAGGAGTCCACA
    2040 ACACTCTGAAAGACGCGACG
    2041 GTCTTAATGTTGGGCAACG
    2042 GTTATCGACTACGCTGTACT
    2043 TCGTGAGACCGTCGTCAGTA
    2044 GACAGCGCAGTACAGGTAAT
    2045 CGTACAGTAAGTATGATGCC
    2046 TAGAGCATCTGACGCTATGA
    2047 GTCACGATTAGTAGGCACG
    2048 TCGTACCTGTATTCAGCGCG
    2049 TTAATCCGCTGTAGCCCAAA
    2050 TTAATTGACTTCGCTCCAGC
  • EXPERIMENTS
  • Arrays containing probes corresponding to SEQ ID NOS 1-2050 were designed and manufactured using known photolithography techniques. Four probes were designed to interrogate each sequence from SEQ ID NOS 1-2050: a probe designed to be the perfect match complement to the sequence (PM), a probe designed to have a central mismatch at position 10 (MM), and probes designed to be the complements to the PM and MM probes (cPM and cMM respectively).
  • FIG. 2 shows an example of the sequences attached to each of the four array features representing a given tag sequence. The first block contains the cPM probe. The second block contains the cMM probe. The third block contains the PM probe—the probe to which the tag is expected to hybridize with the highest affinity. The fourth block contains the MM probe.
  • FIG. 3 shows the array features from the above-described array. The array was hybridized with biotin-labeled oligonucleotide tags, stained with streptavidin-phycoerythrin, and the data was collected with a laser scanner. Four features, organized vertically on the probe array, represent each tag-probe. For each of the four tag-probes shown, arranged horizontally across the array, the brightest hybridization signal is seen with the “PM” feature.
  • FIG. 4 is a scanned image of the hybridization pattern resulting from the hybridization of 2050 different oligonucleotide tags labeled with phycoerythrin to an array designed as described above.
  • FIG. 5 is a scanned image of the hybridization pattern resulting from the hybridization of 50 sequences complementary to SEQ ID Nos. 2001-2050 to an array designed as described above.
  • FIG. 6 shows signal intensities from two different independent experiments in which 2000 biotinylated oligonucleotide tags or 50 fluorescein labeled control oligonucleotides were hybridized to arrays designed as described above. The frequency of results are shown as normalized (to scale of 0-1, in bins of 0.05) natural logarithms of the net signal intensities. The normalized natural logarithm of the signal intensities obtained are distributed about a geometric mean of 0.8 with a standard deviation of less than 0.1.
  • FIG. 7 shows the PM/MM ratios from the data described in FIG. 4 above. More than 98% of the hybridization's yielded a PM/MM ratio greater than 3/1.
  • CONCLUSION
  • The above descriptions are illustrative and not restrictive. Many variations of the invention will become apparent to those of skill in the art upon review of this disclosure. The scope of the invention should, therefore, be determined not with reference to the above description, but instead should be determined with reference to the appended claims along with their full scope of equivalents.

Claims (3)

1-12. (canceled)
13. A method of analyzing a nucleic acid sequence comprising:
attaching said nucleic acid sequence to a nucleic acid tag to form a sequence-tag complex wherein said nucleic acid tag is a sequence chosen from the group consisting of:
SEQ ID NOS: 1-2000;
the complements of SEQ ID NOS: 1-2000; and
hybridizing said sequence-tag complex to the complement of said nucleic acid tag.
14. The method of claim 13 wherein said complement of said nucleic acid tag is attached to a solid support. _
US11/562,548 2000-04-06 2006-11-22 Tag Nucleic Acids and Probe Arrays Abandoned US20080032408A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/562,548 US20080032408A1 (en) 2000-04-06 2006-11-22 Tag Nucleic Acids and Probe Arrays

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US19558500P 2000-04-06 2000-04-06
US09/827,383 US7157564B1 (en) 2000-04-06 2001-04-04 Tag nucleic acids and probe arrays
US11/562,548 US20080032408A1 (en) 2000-04-06 2006-11-22 Tag Nucleic Acids and Probe Arrays

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/827,383 Division US7157564B1 (en) 2000-04-06 2001-04-04 Tag nucleic acids and probe arrays

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/868,247 Continuation US7541757B2 (en) 2003-07-09 2007-10-05 Motor vehicle

Publications (1)

Publication Number Publication Date
US20080032408A1 true US20080032408A1 (en) 2008-02-07

Family

ID=37592266

Family Applications (2)

Application Number Title Priority Date Filing Date
US09/827,383 Expired - Lifetime US7157564B1 (en) 2000-04-06 2001-04-04 Tag nucleic acids and probe arrays
US11/562,548 Abandoned US20080032408A1 (en) 2000-04-06 2006-11-22 Tag Nucleic Acids and Probe Arrays

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US09/827,383 Expired - Lifetime US7157564B1 (en) 2000-04-06 2001-04-04 Tag nucleic acids and probe arrays

Country Status (1)

Country Link
US (2) US7157564B1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012050925A2 (en) 2010-09-28 2012-04-19 Amylin Pharmaceuticals, Inc. Highly soluble leptins

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BRPI0206747B1 (en) 2001-01-25 2017-03-21 Luminex Molecular Diagnostics Inc polynucleotides for use as labels and tag complements, manufacture and use thereof
US7226737B2 (en) * 2001-01-25 2007-06-05 Luminex Molecular Diagnostics, Inc. Polynucleotides for use as tags and tag complements, manufacture and use thereof
EP2298785B1 (en) * 2004-02-06 2012-07-25 Canadian Blood Services Simultaneous determination of blood group and platelet antigen genotypes
EP1647600A3 (en) 2004-09-17 2006-06-28 Affymetrix, Inc. (A US Entity) Methods for identifying biological samples by addition of nucleic acid bar-code tags
US7842794B2 (en) 2004-12-17 2010-11-30 Roche Molecular Systems, Inc. Reagents and methods for detecting Neisseria gonorrhoeae
US8329884B2 (en) 2004-12-17 2012-12-11 Roche Molecular Systems, Inc. Reagents and methods for detecting Neisseria gonorrhoeae
CL2008001682A1 (en) * 2007-06-08 2008-12-12 Monsanto Technology Llc Methods for plant improvement through the use of direct nucleic acid sequence information.
WO2018081113A1 (en) 2016-10-24 2018-05-03 Sawaya Sterling Concealing information present within nucleic acids

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4359353A (en) 1981-05-18 1982-11-16 Hydrocarbon Research, Inc. Polypeptides as chemical tagging materials
US4441943A (en) 1981-05-18 1984-04-10 Hri Inc. Polypeptides as chemical tagging materials
US5149625A (en) 1987-08-11 1992-09-22 President And Fellows Of Harvard College Multiplex analysis of DNA
US5856092A (en) 1989-02-13 1999-01-05 Geneco Pty Ltd Detection of a nucleic acid sequence or a change therein
DE69028402T2 (en) 1989-05-22 1997-04-17 Hoffmann La Roche METHOD FOR MARKING AND DETECTING SUBSTANCES WITH NUCLEIC ACIDS
US5744101A (en) 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US5527681A (en) 1989-06-07 1996-06-18 Affymax Technologies N.V. Immobilized molecular synthesis of systematically substituted compounds
US5800992A (en) 1989-06-07 1998-09-01 Fodor; Stephen P.A. Method of detecting nucleic acids
US5424186A (en) 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
US6040138A (en) 1995-09-15 2000-03-21 Affymetrix, Inc. Expression monitoring by hybridization to high density oligonucleotide arrays
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5252743A (en) 1989-11-13 1993-10-12 Affymax Technologies N.V. Spatially-addressable immobilization of anti-ligands on surfaces
US5324663A (en) 1990-02-14 1994-06-28 The Regents Of The University Of Michigan Methods and products for the synthesis of oligosaccharide structures on glycoproteins, glycolipids, or as free molecules, and for the isolation of cloned genetic sequences that determine these structures
US6013431A (en) 1990-02-16 2000-01-11 Molecular Tool, Inc. Method for determining specific nucleotide variations by primer extension in the presence of mixture of labeled nucleotides and terminators
US5242979A (en) 1990-10-05 1993-09-07 Hercules Incorporated Organosilicon compositions containing hydrocarbon elastomers
US5384261A (en) 1991-11-22 1995-01-24 Affymax Technologies N.V. Very large scale immobilized polymer synthesis using mechanically directed flow paths
US5412087A (en) 1992-04-24 1995-05-02 Affymax Technologies N.V. Spatially-addressable immobilization of oligonucleotides and other biological polymers on surfaces
CA2124087C (en) 1991-11-22 2002-10-01 James L. Winkler Combinatorial strategies for polymer synthesis
US5550215A (en) 1991-11-22 1996-08-27 Holmes; Christopher P. Polymer reversal on solid surfaces
EP1382386A3 (en) 1992-02-19 2004-12-01 The Public Health Research Institute Of The City Of New York, Inc. Novel oligonucleotide arrays and their use for sorting, isolating, sequencing, and manipulating nucleic acids
US5981176A (en) 1992-06-17 1999-11-09 City Of Hope Method of detecting and discriminating between nucleic acid sequences
US5807683A (en) 1992-11-19 1998-09-15 Combichem, Inc. Combinatorial libraries and methods for their use
US5491074A (en) 1993-04-01 1996-02-13 Affymax Technologies Nv Association peptides
US5631734A (en) 1994-02-10 1997-05-20 Affymetrix, Inc. Method and apparatus for detection of fluorescently labeled materials
US5571639A (en) 1994-05-24 1996-11-05 Affymax Technologies N.V. Computer-aided engineering system for design of sequence arrays and lithographic masks
US5604097A (en) 1994-10-13 1997-02-18 Spectragen, Inc. Methods for sorting polynucleotides using oligonucleotide tags
US5846719A (en) 1994-10-13 1998-12-08 Lynx Therapeutics, Inc. Oligonucleotide tags for sorting and identification
US6013445A (en) 1996-06-06 2000-01-11 Lynx Therapeutics, Inc. Massively parallel signature sequencing by ligation of encoded adaptors
US5695934A (en) 1994-10-13 1997-12-09 Lynx Therapeutics, Inc. Massively parallel sequencing of sorted polynucleotides
US5599695A (en) 1995-02-27 1997-02-04 Affymetrix, Inc. Printing molecular library arrays using deprotection agents solely in the vapor phase
US5624711A (en) 1995-04-27 1997-04-29 Affymax Technologies, N.V. Derivatization of solid supports and methods for oligomer synthesis
US5744992A (en) 1995-12-20 1998-04-28 Vlsi Technology, Inc. Digital phase shifter
US6156502A (en) 1995-12-21 2000-12-05 Beattie; Kenneth Loren Arbitrary sequence oligonucleotide fingerprinting
JP3918028B2 (en) 1996-10-14 2007-05-23 フジコピアン株式会社 Thermal transfer recording medium
US5873105A (en) 1997-06-26 1999-02-16 Sun Microsystems, Inc. Bounded-pause time garbage collection system and method including write barrier associated with a source instance of a partially relocated object
US6607878B2 (en) 1997-10-06 2003-08-19 Stratagene Collections of uniquely tagged molecules
US6269846B1 (en) 1998-01-13 2001-08-07 Genetic Microsystems, Inc. Depositing fluid specimens on substrates, resulting ordered arrays, techniques for deposition of arrays
CA2366459A1 (en) 1999-03-26 2000-10-05 Affymetrix, Inc. Universal arrays
US6458630B1 (en) 1999-10-14 2002-10-01 International Business Machines Corporation Antifuse for use with low k dielectric foam insulators

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012050925A2 (en) 2010-09-28 2012-04-19 Amylin Pharmaceuticals, Inc. Highly soluble leptins
EP3241558A2 (en) 2010-09-28 2017-11-08 Aegerion Pharmaceuticals, Inc. Highly soluble leptins
EP3305315A1 (en) 2010-09-28 2018-04-11 Aegerion Pharmaceuticals, Inc. Engineered polypeptides having enhanced duration of action

Also Published As

Publication number Publication date
US7157564B1 (en) 2007-01-02

Similar Documents

Publication Publication Date Title
US20080032408A1 (en) Tag Nucleic Acids and Probe Arrays
US6287778B1 (en) Allele detection using primer extension with sequence-coded identity tags
US6709816B1 (en) Identification of alleles
US6582908B2 (en) Oligonucleotides
US6342355B1 (en) Probe-based analysis of heterozygous mutations using two-color labelling
US6268147B1 (en) Nucleic acid analysis using sequence-targeted tandem hybridization
US7250289B2 (en) Methods of genetic analysis of mouse
US7138506B2 (en) Universal microarray system
EP1645640B1 (en) Method for detecting chromosomal translocations
US20050074787A1 (en) Universal arrays
US20140243229A1 (en) Methods and products related to genotyping and dna analysis
US20130017966A1 (en) Methods for Genotyping with Selective Adaptor Ligation
EP1056889B1 (en) Methods related to genotyping and dna analysis
EP1169474A1 (en) Olignucleotide array and methods of use
US6638719B1 (en) Genotyping biallelic markers
EP1026258A2 (en) Multiplex genotyping of populations of individuals
US20020042069A1 (en) Long-length oligonucleotide microarrays
Steinmetz et al. High-density arrays and insights into genome function
US20030077584A1 (en) Methods and compositons for bi-directional polymorphism detection
KR100429967B1 (en) Method of analysing one or more gene by using a dna chip
Hagedoorn et al. Chemical RNA labeling without 3′ end bias using fluorescent cis-platin compounds
EP1856284B1 (en) Microarray with temperature specific controls
US20080227658A1 (en) Cdna Microarrays With Random Spacers
JP2009125018A (en) Method for detecting haplotype

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION