CN108624683B - Application of USP48 gene mutation in ACTH-type pituitary adenoma molecular diagnosis - Google Patents
Application of USP48 gene mutation in ACTH-type pituitary adenoma molecular diagnosis Download PDFInfo
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- C12Q—MEASURING 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
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- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
Abstract
The invention provides application of USP48 gene mutation in ACTH pituitary adenoma molecular diagnosis, and particularly provides specific gene mutation in ACTH pituitary adenoma patients, namely USP48 gene mutation, and experimental results show that the ACTH pituitary adenoma patients can be diagnosed by detecting the USP48 gene mutation, so that a diagnosis basis is provided for subsequent specific and targeted treatment. The invention also provides application of the mutated gene as a target point for treating pituitary adenoma.
Description
Technical Field
The invention relates to the technical field of biology, in particular to application of USP48 gene mutation in molecular diagnosis of ACTH-type pituitary adenoma.
Background
Pituitary adenoma (Pituitary adenomas) is the most common neuroendocrine tumor in humans, and is also one of the most common brain tumors (incidence is on the 2 nd position). According to their different endocrine properties, they can be classified into prolactin, growth hormone, adrenocorticotropic hormone, thyroid stimulating hormone, hormone-free, and mixed subtypes. The tumor abnormally secretes various hormones, so that the patient has obvious endocrine disturbance symptoms such as infertility, acromegaly, cushing syndrome, hyperthyroidism and the like. The pituitary tumor is hidden and grows slowly, when a patient has clinical symptoms and goes to a clinic, the tumor usually has huge volume and grows invasively and presses adjacent important anatomical structures, so that the patient has nerve function deficiency symptoms such as hypophysis hypofunction, binocular vision reduction, cranial nerve paralysis and the like, the life quality of the patient is seriously influenced, and even the life is threatened.
Pituitary adenomas of adrenocorticotropic hormone (ACTH) type secrete a large amount of ACTH from adrenocorticotropic hormone cells in the pituitary gland, promote the adrenal gland to secrete a large amount of cortisol, finally cause endogenous hypercortisolism, and then produce a series of metabolic disorders and pathological changes, which are called Cushing's disease (Cushing's disease) and account for 85% of ACTH-dependent Cushing's syndrome. Cushing's disease is a serious endocrine disease, which rarely remits itself and has a high fatality rate if not treated in time. The patients mainly show central obesity, hypertension, cardiovascular diseases, metabolic syndrome, osteoporosis and the like. Although the molecular pathogenesis of cushing's disease has been widely studied, the pathogenic genetic mechanism of excess ACTH production remains unclear. Currently, the clinical treatment of pituitary tumors is mainly surgical resection, and drugs and stereotactic radiotherapy are used as assistance, but only a few patients are cured by the methods. Most of the treated cases show tumor recurrence after a short remission period. Furthermore, it was found that ACTH-type pituitary adenomas can present distinct imaging manifestations and clinical phenotypes: part of the tumor has small volume, and the focus is distributed in a dispersion shape, so that the positioning before the operation is very difficult; and part of the tumor has huge volume and grows invasively to the periphery, so that the full resection of the tumor is extremely difficult to obtain in the operation. For different types of pituitary adenomas, different clinical treatment strategies should be applied. There are no specific molecular diagnostic markers available to make them differentially diagnostic.
Disclosure of Invention
The invention aims to provide application of USP48 gene mutation in molecular diagnosis and targeted therapy of ACTH-type pituitary adenoma.
In the first aspect of the invention, the application of the USP48 gene or a detection reagent thereof is provided for preparing a kit for detecting pituitary adenoma or susceptibility thereof.
In another preferred embodiment, the pituitary adenoma is adrenocorticotropic hormone (ACTH) type pituitary adenoma.
In another preferred embodiment, the USP48 gene contains a gene mutation site selected from the group consisting of:
c → A at position 51169;
c → T at position 51169;
t → C at position 51171;
51174 position A → G;
51182 position C → T;
51198 position C → T;
51206 position C → T;
51207 position A → T;
t → C at position 51239;
wherein the nucleotide position numbering is based on SEQ ID NO 1.
In another preferred embodiment, the reagent comprises a primer, a probe, a chip, or an antibody.
In another preferred embodiment, the kit contains one or more reagents selected from the group consisting of:
(a) Specific primers for the USP48 gene;
(b) A specific probe for detecting one or more of the gene mutation sites;
(c) A chip for detecting one or more of the gene mutation sites;
(d) And the specific antibody is used for detecting the amino acid mutation corresponding to the mutation site of one or more genes.
In a second aspect of the present invention, there is provided a use of an isolated polynucleotide containing a mutation site, or a detection reagent thereof, for preparing a kit for detecting pituitary adenoma or a susceptibility thereof, wherein the mutation site is selected from the group consisting of:
c → A at position 51169;
c → T at position 51169;
position 51171T → C;
51174 position A → G;
51182 position C → T;
51198 position C → T;
51206 position C → T;
51207 position A → T;
t → C at position 51239
Wherein the nucleotide position numbering is based on SEQ ID NO 1.
In another preferred embodiment, the polynucleotide is 8-1000bp, preferably 20-500bp, more preferably 30-200bp, most preferably 50-100bp in length.
In a third aspect of the present invention, there is provided an isolated polypeptide encoded by the USP48 gene, said USP48 gene comprising a gene mutation site selected from the group consisting of:
51169 bit C → A;
c → T at position 51169;
t → C at position 51171;
51174 position A → G;
51182 bit C → T;
51198 position C → T;
51206 position C → T;
51207 position A → T;
t → C at position 51239;
wherein the nucleotide position numbering is based on SEQ ID NO 1.
In another preferred embodiment, the polypeptide has amino acid residue mutations selected from the group consisting of:
M415I,M415I,M415V,Y414H,R411Q,G406R,C403Y,C403S,E392G
wherein the amino acid residue numbering is based on SEQ ID NO 2.
In a fourth aspect of the present invention, there is provided a kit for detecting pituitary adenoma, the kit comprising a reagent for detecting the USP48 gene.
In another preferred example, the USP48 gene has a gene mutation site selected from the group consisting of:
c → A at position 51169;
c → T at position 51169;
t → C at position 51171;
51174 position A → G;
51182 bit C → T;
51198 position C → T;
51206 position C → T;
51207 position A → T;
t → C at position 51239;
wherein the nucleotide position numbering is based on SEQ ID NO 1.
In another preferred embodiment, the reagent comprises a primer, a probe, a chip, or an antibody.
In a fifth aspect of the invention, there is provided the use of the USP48 gene or a modulator thereof for the preparation of a medicament for the prevention and/or treatment of pituitary adenomas.
In another preferred example, the pituitary adenoma is an ACTH type pituitary adenoma.
In another preferred embodiment, the modulator is an antagonist or an activator.
In another preferred embodiment, the antagonist inhibits the expression of the gene or inhibits the activity of the gene expression product (protein).
In another preferred embodiment, the activator promotes the expression of the gene or increases the activity of the gene expression product (protein).
In another preferred embodiment, each of the genes has a mutation site shown in Table 1.
In another preferred embodiment, the regulator comprises: small molecule compounds, antibodies, polypeptides, siRNA, miRNA, and the like.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Detailed Description
The inventor unexpectedly finds a specific gene mutation in ACTH pituitary adenoma patients, namely, a mutation of USP48 gene through extensive and intensive research, and the experimental result shows that the ACTH pituitary adenoma patients can be diagnosed by detecting the mutation of the USP48 gene, thereby providing a diagnosis basis for subsequent specific and targeted treatment. The invention also provides the application of the mutated gene as a target point for treating pituitary adenoma.
Before the present invention is described, it is to be understood that this invention is not limited to the particular methodology and experimental conditions described, as such methods and conditions may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. As used herein, the term "about" when used in reference to a specifically recited value means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc.).
Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now exemplified.
USP48 Gene
In a preferred embodiment of the present invention, the polynucleotide sequence of the wild-type USP48 gene is shown in SEQ ID NO. 1;
in a preferred embodiment of the invention, the amino brush sequence of wild-type USP48 protein is as shown in SEQ ID NO. 2.
Gene mutation
Gene mutation (DNA sequence variation) is a change in the structure of a gene due to the addition, deletion or substitution of base pairs in a DNA molecule.
The site of the gene where the gene mutation occurs is the mutation site herein, and the addition, deletion or substitution of bases can occur at the mutation site.
For example, "chr1: g.22056252C > T" indicates that the g.22056252 site on chromosome 1 of human is mutated from C to T.
One class of genetic mutations is SNV, a single nucleotide variation.
Single Nucleotide Variation (SNV)
Single nucleotide variations, which are variations of DNA sequences in the human genome, are gaining increasing importance in a variety of biological and biomedical applications. SNVs can be used to explore human population evolution history, analyze forensic samples, and thus play an important role in genetics. Pharmacogenetics utilizes these DNA variations to elucidate the underlying genetic factors that constitute different drug efficacies or adverse events.
The present invention relates to the identification of Single Nucleotide Variants (SNVs) of a particular disease, which are specifically identified as being associated with pituitary adenomas, and thus, or prior to the presence of disease symptoms, these individuals may be subjected to interventions such as dietary changes, exercise and/or drug therapy. The identification of SNVs involving pituitary adenomas helps to better understand the disease process, improve diagnostic and therapeutic agents.
As used herein, the term "SNV" refers to a single nucleotide variation at a specific location in the human genome that differs between populations of individuals. In the present invention, the SNV may be determined by its name or by the position located in a specific sequence. For example, SNV "[ G/A ]" indicates that the nucleotide base (or allele) at that position in the sequence may be guanine or adenine.
As used herein, an INDEL INDEL marker refers to a difference in the genome of two parents across the entire genome, wherein one parent has a certain number of nucleotide insertions or deletions in its genome relative to the other parent.
As used herein, the nucleotide sequences disclosed herein include the complement of the nucleotide sequence. In addition, the term "SNV" includes any allele in a set of alleles.
As used herein, the term "allele" refers to a particular nucleotide in the selection of nucleotides that define SNV.
As used herein, the term "at-risk allele" refers to an allele associated with pituitary adenoma disease.
As used herein, the term "haplotype" refers to a combination of specific alleles from two or more SNVs.
As used herein, the term "at-risk haplotype" refers to a haplotype associated with pituitary adenoma disease.
The specific genes and the mutation sites contained therein are shown in Table 1. Unless otherwise specified, the numbering of the loci of the present invention is based on the human genome sequence (UCSC) hg19 version.
Polynucleotides comprising mutation sites
The invention also provides polynucleotides comprising the mutation sites of the invention. In a preferred embodiment of the present invention, the present invention also provides a vector, a host cell containing the polynucleotide.
As used herein, the term "polynucleotide" refers to a polymorphism of nucleotides of any length. Polynucleotides may contain deoxyribonucleotides, ribonucleotides, and/or their analogs. The polynucleotide may have any three-dimensional structure, including single-stranded, double-stranded, and triple-helical molecular structures, and may perform any known or unknown function. As in the following non-limiting examples: genes or gene fragments, exons, introns, mRNA, tRNA, rRNA, siRNA, ribozymes, cDNA, recombinant polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, primers. Polynucleotides may also include modified nucleic acid molecules, such as methylated nucleic acid molecules and nucleic acid molecule analogs.
In another preferred embodiment, the polynucleotide itself may further comprise a detection reagent for detecting the polynucleotide, including a primer, a probe, an amplification product, or a plasmid.
As used herein, the term "substantially isolated" or "isolated" polynucleotide refers to a polynucleotide that is substantially free of naturally associated sequences. Substantially free means at least 50%, preferably at least 70%, more preferably at least 80% or optimally at least 90% free of other naturally related materials. An "isolated polynucleotide" also includes recombinant polynucleotides.
As used herein, the term "hybridizes under stringent conditions" is intended to describe hybridization conditions under which nucleotide sequences that are at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 98% identical to each other typically remain hybridized to each other. These stringent conditions are known to those skilled in the art and can be found in Current Protocols in Molecular Biology, john Wiley & Sons, N.Y. (1989). One non-limiting example of stringent hybridization is hybridization in 6 Xsodium chloride/sodium citrate (SSC) at about 45 ℃ followed by one or more washes in 0.2xSSC,0.1% SDS at 50-65 ℃.
The term "primer" as used herein refers to a generic term for an oligonucleotide which, when paired with a template, is capable of synthesizing a DNA strand complementary to the template from its origin by the action of a DNA polymerase. The primer can be natural RNA, DNA, and any form of natural nucleotide. The primers may even be non-natural nucleotides such as LNA or ZNA etc. A primer is "substantially" (or "substantially") complementary to a particular sequence on one strand of the template. The primer must be sufficiently complementary to one strand of the template to begin extension, but the sequence of the primer need not be completely complementary to the sequence of the template. For example, a primer that is complementary to the template at its 3 'end and has a sequence that is not complementary to the template at its 5' end remains substantially complementary to the template. Primers that are not perfectly complementary can also form a primer-template complex with the template, so long as there is sufficient primer binding to the template, allowing amplification to occur.
As used herein, the term "vector" refers to a DNA molecule that can carry inserted DNA and can be maintained in a host cell. The vector may also be a cloning vector, cloning vehicle, or the like. The term "vector" includes vectors whose primary function is to insert a nucleic acid molecule into a cell, replicating vectors whose primary function is to replicate a nucleic acid, and expression vectors for transcription and/or translation of DNA or RNA, as well as vectors that provide more than one of the above functions.
As used herein, the term "host cell" refers to a single cell or cell culture that may be or has been the recipient of vector or nucleic acid molecule and/or protein integration. Host cells include progeny of a single host cell, and the progeny may not necessarily be identical (in morphology or in total DNA complement) to the parent due to natural, random, or deliberate mutation. Host cells include cells transfected with a polynucleotide of the invention. An "isolated host cell" refers to a host cell that has been physically separated from the organism from which it was derived.
The host cell may be a prokaryotic cell, such as a bacterial cell; or lower eukaryotic cells, such as yeast cells; or higher eukaryotic cells, such as mammalian cells. Representative examples are: coli, bacterial cells of the genus streptomyces; fungal cells such as yeast; a plant cell; an insect cell; animal cells, and the like.
Transformation of a host cell with recombinant DNA may be carried out using conventional techniques well known to those skilled in the art. When the host is prokaryotic, such as E.coli, competent cells, which are capable of DNA uptake, can be harvested after exponential growth phase and subsequently treated with CaCl 2 Methods, the steps used are well known in the art. Another method is to use MgCl 2 . If desired, transformation can also be carried out by electroporation. When the host is a eukaryote, the following DNA transfection methods may be used: calcium phosphate coprecipitation, conventional mechanical methods such as microinjection, electroporation, liposome packaging, etc.
Kit and application thereof
The invention also includes a kit for detecting pituitary adenoma or a predisposition therefor, said kit comprising primers for specifically amplifying an amplification product comprising a mutation site. More preferably, it further comprises an agent selected from the group consisting of: (a) a probe that binds to a mutation site; (b) a restriction enzyme recognizing the mutation site.
It is understood that after the present invention discloses for the first time the relevance of the mutation site of the present invention to pituitary adenoma, one skilled in the art can easily design an amplification product that can specifically amplify the mutation site, and then determine whether the mutation site exists by sequencing or the like.
In general, the length of the primer is 15-50bp, preferably 20-30bp. Although complete complementarity of the primer to the template sequence is preferred, it is known to those skilled in the art that specific amplification (i.e., amplification of only the desired fragment) is also possible in the presence of a primer that is not necessarily complementary to the template, particularly at the 5' end of the primer. Kits containing these primers and methods of using these primers are within the scope of the invention, provided that the primers amplify an amplification product containing the corresponding position of the mutation site of the invention.
Although the length of the amplification product is not particularly limited, the length of the amplification product is usually 10 to 3000bp, preferably 30 to 2000bp, more preferably 50 to 200bp.
One object of the present invention is to provide a kit for detecting a tumor subtype of a patient with pituitary adenoma of ACTH type to be detected.
The kit provided by the invention comprises a comparison card for recording the detection standard and a sequencer;
the detection criteria are as follows:
if the full length of the USP48 gene or a partial fragment sequence thereof in the tumor of the ACTH type pituitary adenoma patient to be detected is not completely consistent with the wild type full length sequence or the corresponding partial fragment sequence of the USP48 gene, the tumor of the ACTH type pituitary adenoma patient to be detected is or is selected as ACTH type pituitary adenoma mutant; if the full length of the USP48 gene or a partial fragment sequence of the full length of the USP48 gene in the tumor of the ACTH-type pituitary adenoma patient to be detected is completely consistent with the full length sequence or the corresponding partial fragment sequence of the USP48 gene, the tumor of the ACTH-type pituitary adenoma patient to be detected is or is selected as ACTH-type pituitary adenoma wild type;
the wild type sequence of the USP48 gene is a sequence 1 in a sequence table.
The kit also comprises a set of primers for amplifying the full-length or partial fragment of the USP48 gene.
Each primer or primer pair or each primer therein is packaged independently, and each primer pair is used independently.
Another objective of the invention is to provide a set of primers for assisting in detecting tumor subtypes of a patient with ACTH pituitary adenoma to be detected.
The complete set of primers provided by the invention consists of a primer pair 1, a primer pair 2 and a primer pair 3;
the primer pair 1 consists of a single-stranded DNA molecule shown in a sequence 3 in a sequence table and a single-stranded DNA molecule shown in a sequence 4 in the sequence table;
the primer pair 2 consists of a single-stranded DNA molecule shown as a sequence 5 in a sequence table and a single-stranded DNA molecule shown as a sequence 6 in the sequence table;
the primer pair 3 consists of a single-stranded DNA molecule shown in a sequence 7 in a sequence table and a single-stranded DNA molecule shown in a sequence 8 in the sequence table.
The application of the kit or the primer set in the preparation of products for detecting or assisting in detecting the tumor subtype of the patient with ACTH pituitary adenoma to be detected is also within the protection scope of the invention.
The third purpose of the invention is to provide a kit for auxiliary detection of whether the tumor of a patient to be detected with pituitary adenoma is ACTH type.
The kit provided by the invention comprises a comparison card for recording the detection standard and a sequencer;
the detection criteria are as follows:
if the full length of the USP48 gene or a partial fragment sequence thereof in the tumor of the pituitary adenoma patient to be detected is not completely consistent with the full length sequence of the wild type of the USP48 gene or the corresponding partial fragment sequence, the tumor of the pituitary adenoma patient to be detected is selected as the ACTH type pituitary adenoma; if the full-length or partial fragment sequence of the USP48 gene in the tumor of the pituitary adenoma patient to be detected is completely consistent with the wild full-length sequence or the corresponding partial fragment sequence of the USP48 gene, the tumor candidate of the pituitary adenoma patient to be detected is not ACTH type pituitary adenoma;
the wild type sequence of the USP48 gene is a sequence 1 in a sequence table.
The application of the kit or the primer set in the preparation of a product for assisting in detecting whether the tumor of a patient suffering from pituitary adenoma to be detected is ACTH type is also within the protection scope of the invention.
Experiments of the invention prove that the USP48 gene mutation is specific to ACTH type pituitary adenoma, and the gene mutation is not seen in other types of pituitary adenomas. Whether the pituitary adenoma is an ACTH subtype can be judged by the aid of whether the USP8 gene is mutated or not, so that different clinical treatment strategies can be adopted in time.
The main advantages of the invention are:
(1) The invention discloses USP48 gene mutation related to ACTH pituitary adenoma for the first time;
(2) The gene mutations disclosed in the present invention have a very high association with ACTH pituitary adenomas and can therefore be used for the diagnosis of pituitary adenomas or a predisposition therefor.
The present invention will be described in further detail with reference to specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Experimental procedures for conditions not specified in detail in the following examples are generally carried out under conventional conditions such as those described in molecular cloning, A laboratory Manual (Huang Petang et al, beijing: scientific Press, 2002) by Sambrook. J, USA, or under conditions recommended by the manufacturer. Unless otherwise indicated, percentages and parts are by weight. The test materials and reagents used in the following examples are commercially available without specific reference.
Example 1
In this example, 22 patients with wild-type pituitary adenoma USP8 (ACTH type) diagnosed in 2010 to 2015 in neurosurgery of warrior, were selected and subjected to whole exon sequencing to obtain a mutant gene profile. Each patient had not undergone surgery, radiotherapy or drug treatment before surgery, and each patient had a definite diagnosis before surgery and was confirmed by the pathology after surgery. All patients entered the study and signed informed consent, which was approved by the ethical committee for medical and scientific research in Huashan Hospital.
Transspherioendoscopic prolapsed adenoma resection
After the patients are clearly diagnosed, they all go through the butterfly endoscope prolapsed adenoma resection, and if the tumor location before operation is not clear, they all go through the nerve navigation location during operation. After the general anesthesia succeeds, the patient takes the supine position, cushions under the shoulders, leans 15 degrees backwards, fixes the head frame, performs navigation, registration and positioning, and performs the conventional disinfection and paving in the operative field. The bilateral nasal mucosa is converged by epinephrine under an endoscope, the nasal septum mucosa is cut about 1cm from the opening of the sphenoid sinus, the fractured bony nasal septum is pushed to the opposite side, the front wall of the sphenoid sinus is exposed, the front wall of the sphenoid sinus is bitten to form a bone window with the diameter of 1.5cm, the position of the saddle bottom is determined under navigation, the bone at the saddle bottom is ground, the bone window with the diameter of 1cm is bitten to form, the dura mater at the saddle bottom is cut through an electrocoagulation cross, the tumor is probed according to MRI and navigation positioning before an operation, the tumor false envelope is firstly stripped, the envelope is removed outside the envelope, the tumor false envelope is completely stripped as much as possible, and the total resection under the endoscope is achieved. Meanwhile, the normal pituitary tissues at the opposite side are probed, so that tumor foci are definitely not seen, and no cerebrospinal fluid leakage is definitely caused. After tight hemostasis, the tumor cavity was packed with gelatin sponge, the saddle bottom was sealed with artificial dura mater, 8cm expansion sponge was packed in both nasal cavities, and the nasal septum was repositioned. If the tumor tissue is not clear during the operation, the pathological section is clear by quick freezing during the operation.
Postoperative pathological HE and immunohistochemical staining
The tumor sample is frozen at-80 deg.c in some part and then pathological specimen is further processed through HE and immunohistochemical staining. The final diagnosis of the pathology was done and consistent by two skilled neurologists, evaluated independently from HE staining and immunohistochemical results. Immunohistochemistry used sections containing more than 90% of tumor cells. Firstly, preparing a tissue slice with the diameter of 5 microns, and sequentially putting the tissue slice into dimethylbenzene and alcohol for dewaxing treatment. After deparaffinization the sections were placed in a methanol solution containing 3% hydrogen peroxide for 20 minutes to block the activity of endogenous peroxidase (HRP). After antigen retrieval, the tissue sections were serum-blocked and incubated with primary and secondary antibodies. After washing, tissue sections will be stained as described in the ABC staining kit (Vector Laboratories, inc.) and tested for HRP activity using the DAB kit (Vector Laboratories, inc.). The sections were counterstained with hematoxylin and finally dehydrated and mounted.
Full exon sample preparation, sequencing and result analysis running software
(1) DNA extraction
DNA extraction was performed on fresh tumor tissue or peripheral blood samples using the AllPrep DNA/RNA Mini kit from Qiagen. For formalin-fixed, paraffin-embedded samples, DNA was extracted using the QIAamp DNA FFPE Tissue kit (Qiagen, usa). The concentration and purity of the DNA was checked by the Qubit dsDNA HS Assay kit with a Qubit 2.0 fluorometer (Life Technologies, inc.) before DNA library construction. A portion of the DNA was removed and analyzed by Mass ARRAY (Sequenom), and compared to the established 48 SNV genotyping sites, again confirming that the tumor and control blood samples were derived from the same patient.
(2) DNA library establishment and on-machine sequencing
And preparing a library for the DNA of the sample qualified for detection. DNA was randomly fragmented into fragments of 200-300bp in size using a Covaris E-220 model sonicator (Covaris) and the fragments were purified using Agencour AMPure XP magnetic beads (Beckman), washed free of impurities and non-fragmented fragments. The two ends of the fragment are respectively connected with barcodes for identification to obtain the target fragment. The adaptor ligation products (200-300 bp) were used with Agencourt AMPure XP beads were further purified and amplified by ligation-mediated polymerase chain reaction (LM-PCR). The products thus produced were pooled into the initial library. Using Illumina TruSeq T The obtained whole exon fragments were captured by an exon enrichment kit of M (62 Mb Illumina). The captured LM-PCR product was evaluated for capture efficiency and for the length of the fragment of interest using an Agilent 2100 bioanalyzer (Agilent). The 22-pair ACTH pituitary tumors and paired blood samples that were completed in the library were sequenced on the computer using HiSeq2500 platform (Illumina).
(3) Results analysis software and conditions
Just after the machine sequencing the raw data first passed through FastQC v0.11.2 (http:// www. Biolin f ormatics.bbsrc.ac.uk/projects/fastqc) A stringent quality control check was performed and the low quality sequences were filtered using trimmatic v0.30 software. Quality control filtered sequences were compared to human genome sequences (UCSC, hg19 version) using the Burrows-Wheeler Aligner algorithm (default parameters) in BWA v0.7.7 software, and the data were compared using Picard v1.110 MarkDuplicate subroutine (see Table V1.110)http://picard.sourcefNet) were subjected to a de-duplication process. Then, the primers Indel reaction and BaseRecalibrator of the genome analysis kit (GATK) v2.8-1 are used for respectively correcting the quality of Indel regions and bases which are prone to mismatching, and peripheral blood is used for comparing tumors to eliminate personal germline mutation. The SNV is detected by MuTect v1.1.5 software, and the specific parameters are set as follows: the contamination rate is less than 10%, and the minimum base mass fraction is 20. Somatic insertion deletion mutations were detected using VarScan v2.3.6 software with default parameters: strand filtration with a minimum base mass fraction of 20, tumor purity of 90%, copy number abnormalities were also detected with this software, with parameters set as defaults. The following false positive site filtration was performed according to the following criteria: (1) the minimum sequencing depth of the tumor sample and the normal blood sample is 10 layers; (2) the sequencing depth of the tumor mutation site is more than 4 layers; the proportion of the tumor mutation sites is more than 20%. The above standards are all written and executed in Perl scripts. False positive filtered sites, then human were performed using visualization tools in conjunction with a genomics viewer (IGV, broad institute, cambridge, MA, USA)The workers check one by one. Finally, all high quality mutation sites were annotated with Annovar software databases such as RefSeq, dbSNV v138, 1000 genes Project, and COSMIC database v79 for predicting changes in the sequence of the encoded protein (such as synonymous mutations, missense mutations, nonsense mutations, cleavage sites, etc.) and filtering the more common mutation sites in humans.
The finally determined mutation sites are shown in Table 1.
TABLE 1
Example 2 ACTH pituitary adenoma detection kit
Based on the correlation between the mutation site of the present invention and pituitary adenoma, primers for the mutation sites in Table 1 above were designed using methods conventional in the art, and amplified and detected using a DNA sample of a patient as a template. The prepared detection kit contains the primers and PCR reaction liquid.
Dozens of pairs of primers aiming at USP48 gene are designed, and through screening, the primer pairs with good specificity and high amplification efficiency are finally obtained as follows:
primer pair 1:
F:TGCCTGCTATAATCCTGGAAA(SEQ ID NO.3)
R:TCAGCAGAACCTTCTAAGTCTCA(SEQ ID NO.4)
and (3) primer pair 2:
F:CTGGAAAACTGCTTTACCTGGAA(SEQ ID NO.5)
R:AGCCCCGCTAAAGAATAAACAAA(SEQ ID NO.6)
and (3) primer pair:
F:TGCCTGCTATAATCCTGGAAAACT(SEQ ID NO.7)
F:CTCAGCAGAACCTTCTAAGTCTCA(SEQ ID NO.8)
and (3) primer pair 4:
F:CATTCTAAAACATTTGCCTGCT(SEQ ID NO.9)
R:GCCCCGCTAAAGAATAAACA(SEQ ID NO.10)
example 3 Pituitary adenoma susceptibility-assisted detection
200 samples of patients known to have pituitary adenomas (100 of the patients with ACTH-type pituitary adenomas) and 200 samples not having pituitary adenomas were randomly obtained using the kit and the general method in example 2. The two groups of samples are mixed, and the existence of mutation sites in all samples is detected by a random double-blind method, and the result is compared with the result of a sample known to have a disease.
The results of the examination showed that 18 samples contained the mutation site of the present invention, and 15 of them were confirmed to be derived from a subject having an ACTH-type pituitary adenoma by a conventional method.
Therefore, the mutant site of the present invention has a very strong correlation with ACTH-type pituitary adenoma, and the use of the mutant site can effectively diagnose, predict and evaluate pituitary adenoma or susceptibility thereof.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.
Sequence listing
<110> Shanghai university of transportation
Huashan Hospital Attached to Fudan University
Application of <120> USP48 gene mutation in ACTH-type pituitary adenoma molecular diagnosis
<130> P2016-1827
<160> 10
<170> PatentIn version 3.5
<210> 1
<211> 104605
<212> DNA
<213> human
<400> 1
ttctgatagg tagtcagatt ttttattttc aaacgtgcca ggtacatttc ccacttttga 60
ataacagcaa aaccggaaga ggatgctttc acacataata aatgttctcc atcctttctg 120
aaatgcacca aagcaaaaag cctctgaagt caaaacatga gacataattc cttgctcatt 180
gcaggagaca tgcaggtgcc ccctccttta cccaatacca agagacagac ggccgggcag 240
gtgtaaggcg ggtggcgctg cagctgacat ggagaagagt ctaaatctga agacactttt 300
ccacacttag gacaagttct tcactttcat gctttattga aagtagaata tgaatcaaag 360
acaggcattg gtaagcaggt tatgtctcta aaattacttt tcgttcagag cagaatgttg 420
tcccatctac ttgatacaat cctttatgga ccaacgcatc tggtatgaaa ctcgagcaag 480
gaaatataac agaactttat tcccctccca cgactataaa tctcatatgt aaacatgatt 540
tactattact gctactaaac ttgttccgtc tttacttgcc ccctcccacc caccaccccc 600
cttaaatata aaattggaaa catttccttc aagtctgatg tccatcagtg caatctgctt 660
tatttgacat aaggcatttg ggacagtcac gtttgaatgg atttctgcct tttggaaggg 720
gcatgtaatg gtttaattct taaatccacc tttgctttaa tgccctaaca tgtcaaactc 780
ctcttcccct ctggtcattt cttagcagtc agcaagtatt caaagattaa tgtccaagaa 840
gaccagtacc tgggaaaaga aacacacgtg gagggatagt tgtgaactac agattaaaag 900
ttcatggatt ccatttacca agaacacatc atcaacaggg agcatcaaat ttaataaatg 960
aacacagtcg caccttggtg tgggaggata agacaaaata ccagcagact ccaggctctc 1020
cgctaaatca catttttgtt gaaagccatg tgcttcctaa gtgtatcttc acacaaacta 1080
accagatttt attgattctt tcatttaatg accattcttc ttttctgaga gtttcactct 1140
tgtcgcccag gctggagtgc agtggtgcaa tcctggctca ctgcaacctt atctcccagg 1200
ttcaagcatt ctcctgcctc agcctcccaa gtagctgaga ttacaggcgc acgccaccat 1260
gcccggctaa tttttgtatt tttagtagag atggggtttc accatgttgg ccagactggt 1320
ctcgaactcc tgacctcaag tgacccaccc gtctcaacct ccaaaagtgc tgggattaca 1380
ggcgtgagcc accatgcccg gccaatgacc atttttcata aagacgtttt ttgctttgtt 1440
ttgaccccat caggagtccc tttgtaatgg tagcatgcag acaacacagc tgcagcaaga 1500
ggaagacttt attttggcca gtagatttgt ctctcatttg ctttagcaag gaatagctgg 1560
tatgtgattc aaagtcattc cttagaaaat cacaacctgc caggggcttc tggagtggcc 1620
agcaaagaat caagacagca acaggaaaat ccgaaaacgt cagaggtctg tatttgatga 1680
cttcttgaat attatcggtg tgcacaacta catggcccag atgtagtacg agcaccaccg 1740
tgtctcctct tgaagtaata atccaacaaa tgccttaatg ctaagtgatt aattaaatct 1800
tttcactgga cttgataaaa cctgacaaat tcttgtgcca ctaattctta atagttacac 1860
actgttttgc tctaggaggg gacttgatag gaagaactgg gaaaaggtta aaaataaatc 1920
ttgaaatgcc actagctaat ttcccaacct cccataaaat gagaaaggga aggccaaatg 1980
gacatctggc aagaaacagt tctaacacaa aagccccagc tgaggcccca tttgaggcct 2040
gagtgttgaa aaagataatg aagaagcttg agtaagaaat gcatttaact aaaattaatt 2100
tcagtcatga gactcagatt ggattaaaat ttaaaatcaa attatagcct tcgctttaac 2160
agaaaattac aggatgactc tgacattcat gaacaaaaca tgacaaatgt aacttacctt 2220
taaacccttc ttctggcata caaactgaaa aaaagaaaaa aagaagaatt ccaaattgaa 2280
aagattgtcg tgacagacag taatatcatt tcaatgctta aagacaaaag tttaaaataa 2340
cttttgatta cctttgtcac ctgtaataat catctttgaa gttacggatg ttactaattt 2400
cagaacaatc tttgtttctg tttttatcaa agcaatacgt atgcatcatt taaaaagtca 2460
aatactgaca ggacaaggtt tgtaactagg gcacacctag tgcacgactc taggagtggc 2520
ctgggaggaa gccatgtaac tgactcctct ggagctgtct ctctcccctt cctcctccca 2580
ttcccaagtt ctggaaggag tcacttttga ctcacacagc agcttcttct ggtatttagc 2640
ctatttctaa ataacatgct tttcataatt ttatttactt tttttttttg agagggtgtc 2700
cagctctgtc acccagaatg gagtgcagtg gcatgatctc ggctcactgc aacctctgct 2760
tcctgggttc aagcaattct cctgcctcag cttcccaagt agctgggatt acaggcaccc 2820
accaccacac ttggctaatt tttgtatttg tagtagagac agggtttcac cacgttggcc 2880
aggctcgtct cgaactcttg acctcaagtg atccgcccgc cacagcctcc caaagtgatg 2940
ggattacagg agtgggccat cgtgcctggc ctacttcata attttagata aaaatctaat 3000
aaattcttca gtgaaggata caaacagctg ttttaccact tacatagcac ctgccccgac 3060
ccatcctcct gatgaagtgg tgtttgttgt tgttaagcca gtctccagcg ctggcattac 3120
tttttacgcc attaatacta gtcacagttg aatgccttgg tgcaccttgg ttatatttac 3180
tacatggtat gacttggtct ttctgggctt ggtaactact gaattactga tgtgtttcat 3240
tttctctgta tttatctcca attcacgtgt aaattcttaa agacctgtaa cctcttgaag 3300
acagtcatca tcccttccac ttttccttgt ggcatccctt cctgaagctc gcatcccacc 3360
actccaatat ggatcaggtg tcttcgctgc ctgctgaaga acagtagttc tgagacttcc 3420
cttcaccatc ttctagggca tcttatccta ggctgatctg ctatttactg ggtccactgt 3480
tgattctttc ttgatttaat gtttaagaag aagaacacat cctcacacag tatcatggca 3540
gacggtgcat gacagatcaa tcttttgaag ccctgaatat gttcaagggg ccatcaggtg 3600
tgagggttac agacttatag attggaactt gctttccctc aggatcttgc gggcactgct 3660
ctattatctt cctgacttca tcctgtgaat ttgactggct ttccctccta cttctagatg 3720
ctttcatgac cctcttaccc ttagtttttt acttactata tcaaacccag ggtaccatca 3780
ttttttacat ttccatgaac tctcttctat gctccaaatg ttccttttat atagttcctc 3840
ttcctattgt ttgctttttt tttttgccat tatttatagg ttattttcca gctttcttat 3900
gcttcctatg ctatttcctc gacatatctt ggtcccaggc tctcattcct caactatctg 3960
actgctcata tttacttaag tatgaggtac taaaaagatt tgtgggccag gcgtagtggc 4020
tcacgcctgt aatctcagca cactgggagg ccgaggcagg cggatcatga ggtcacgagt 4080
tccagagcag cctggacaac atagtgaaac tctgtcccta ctaaaaatac aaaaattagc 4140
tgggcatggt ggcaggcgcc tgtagtccca gctacttggg aggctgaggc agaagaatcg 4200
cttgaaccca ggacggggag attgtagtga gccaagatca tgccactgca ctccagcttg 4260
ggcaactgtg agactccatc tcagaaaaaa aaaaaaaaag atgtctgaaa gctctgttca 4320
gtgggcactg gtgggattga ctaaagggtg cctgggacat gaaccagctt taaaaaaaat 4380
acaaacaagg ccaggtgcaa tagctcacat ctgtaatcca aacacttcgg gaggccgaga 4440
tgggcagatc acctgacgac aggaatttga gaccagcctg gcgaatatag tgaaaccccg 4500
tctctaccaa aaatacaaaa gttagccagg catggtgttg catgcctata gtcccagcta 4560
ctactcagga ggctgagcca ggagaatcac ttgaagccca gaggcggagg ttgcagtgag 4620
ccatactgca cttcagcctt ttgagactcc atctcaaaaa aataaaaaat aaaaaataaa 4680
agccaaacat aatatttgta catatttatg gggaacagct tatattttga tacatgcata 4740
cagtgtataa tgatcacatc agggtattta gttatctcca tcaccttgaa tatttattat 4800
ttcttctttt ttgagacagg gtctcaatct gtcacccagg cttgagtgta gtggcatgat 4860
gacagctcac tgcagcctcc aactccccgg ctcaagcaat ccacccacct cagcctccca 4920
agtatctgag accacaggtg cgagccacca tgcctggctc tttttttaaa atttgtagta 4980
gagacagggt ctcactatgt tgcccaggtt ggtcctgaac tcttgggttc aagtgatcca 5040
ctgcgcccgg cctatcattt ctttgtgttg ggaacattgc attatctttt cttctagctc 5100
ttttgaaata tacaacatat caccctactg tactactgaa taccagaact tattctttct 5160
atcaaattgt atgtttgtac ccattaacca acctcccttc atatggcccc tttcccatcc 5220
actcataact accattctac agccaaaaga tcagcttttt tagctcctac gtatgagtga 5280
gaaaatacag tattgtcttt ctgagcctgg cttatttcac ttaacataat gtcctccagt 5340
tccacccatg ttgctgcaaa tgacaggatt tcattttttt aatggctgaa taatagtatc 5400
ccattgtatg tctacatata aatataacat atcaaggcat ctactgatgg acatgtaggt 5460
tgattccata ccttggctgt tgtgaacagt gctgcaataa acatgagagt gcaaatatcc 5520
tttcgataca ctgatttctt ttcctttgga taaataccac tagtgggatt gctggatcat 5580
atggtagtta tatttttagt tttctgagaa acttccatac tgttttccat aatggctgta 5640
ctaatttaca ttcccaccaa aagtccgtat aagagttccc ttttctctgc atcctagtta 5700
catgttattg tctttttgat aatagccatg ctaactgata agatggtatc tcactgtgat 5760
tttgatttgc atttccctga tgattagtga tgctgagcat ctttcataca cctattggcc 5820
atgtttatgt cttcttttga gaaatgtctg ttcaggtccg ttgcctactg tttaatgaga 5880
ttatattttc tcccattcta caggttgtct cttcaactct gcagattatt tcctttgctg 5940
tgcagaagct ttttagttta atatagtcca tttggttatt tttggttttg ttccctgtgc 6000
tttgaggtct cagctaaaat ctctgtctag accaatgttt gacagcattt cccccatatt 6060
gaattctagc aatttcatag tttcaagtct tacatttaag tctttaatcc attttgagtt 6120
gattttaata tatagtgaga gacagaggtc tagtctcatt tttctgcata tcgatatcca 6180
gttttcccag caaaatctag tgaagagggt gccctttccc cagtgtatgt tcttggtgcc 6240
tttgtcataa attagttggc tgtaaatacg tgaatttatt tttgggttct ttattctgtt 6300
ccattgtcct atgttttata ccaataccat gctgtttagg ttaccatagc tttgtagtat 6360
attttgaaac caggtagcat gatgcctcca gctttgttct ttttgctgag gattgatttg 6420
gctattcagg gtcttttgtg gttccatatg aattttagga ttgtgttttt ctatttctgt 6480
gaggaatgtc attggtattt tgataggaat tgcatttaat ctgcaggtta ttttgggtaa 6540
tatggtcatt ttaacaatat taattcttct gatccatgag cacaggatat ctttccattt 6600
gtttgcatct ttcaatttct tacattagtg ttttgtagtt ttccttgtag aggtctttca 6660
ccttcttggt taaatttatt cctaagtatt taatcttatt tttttttgta gctattatta 6720
ttggaattgc tttcttttct tttttttttt tttgagatgg agtctgtcat ccaggctaga 6780
gagtgcagtg ctgcgatctt ggctcactgc atccactggg ttcaagcaat tctcctgcct 6840
cagcctccct agtaactggg attacaggca tgcgctacta cgcctggtta atttttgtaa 6900
ttttagtaga gatggggttt cgccatgttg gccaggctgg tcacaaactc ctgacttcaa 6960
ctgctccact tgcctcaccc tcccaaagtg ctgggattac aggcatgagc cactgcgccc 7020
agccgctttc ttgatttctt tttcagctag ttcttattga tgtatagtaa tgctgctaat 7080
ttttgtatgt tgatttttgt taggtaaaca tgataatcac tacactacag aaactcactt 7140
tgtacactga tttttgtatc ctgcaatttt actgaatgtt catcagttgt ttaagagtgt 7200
tttggtggcg tctttaggtt tttctacata tataagatca tgtcagcctg gcatggtggc 7260
tcatgcctgt aattctagca ttttgggagg cccaggtggc cagatcacag ggggccagga 7320
gttcgggacc agcctggcca atatgggaaa tcctcatctc tagtaaaaat acaaaaatta 7380
gctgggtgtc atggcacatg cctgtagtcc cagctactca ggagtctgag gcacaagaat 7440
tgcttgaacc caggagtggt ggctgcagtg agctgagatg gtgccactgc actccagtct 7500
gggcaacaaa gactctaaaa aaaaagcatg tcatctgcaa agagggacca tttgacttcc 7560
tcttttccaa ttttgcatgc tttttactta tttatcttgc ctaattgctc ttgctaggac 7620
ttccaatact atgttgaata agagtggtga aaatggccgt ccttgtctat tccagttctt 7680
agaggaaagg ctttaagctt ttcgccatta ggtatgatgt cagctgtggg tctcacatat 7740
ggcctttatt atattgaggt atgttccttc tgtacttggt tttttgagag tttttaccac 7800
gaagggatgt tgaattttat caaatgcttt ttctttgtct attaagatga tcatatgatt 7860
tttgtccttc attctgctga tgtgatgtat tggtttgcat atgttgaaca tccttgcatc 7920
cctgggagaa atctcacttg atcatacaga accagacttt ttacatccac tggttatttt 7980
cttgactagt ttccctggag agaaatccct tcccacctgg gggagggtaa gtaatgggct 8040
gcccgaattt gagcaaaggg ctaagagatg gtctcctatt tggtataggc ttcgttccca 8100
cctttctagt ttaatttttc caagtgtgga aacacataat tctgggtgcc catctgaggt 8160
ccaggtggag atggggaagt gacaaggatg tgaaaggtag agagttgtct aactgcttct 8220
tatacagttt tccaaacaag tatcatgtta tcttcttttt aggctcacaa ttcattccca 8280
ccttcagagg tacctaggcc tctaatttgt gtgtgcctgt ctggggcact gcaatctgac 8340
ttagttttgc ttcttgttga cctcctccac aggcagagct cacatttatt tcagtttcct 8400
caggttagct ttccaagttt ttgtagatat ctttccctcc tttctatgat cttttaagat 8460
aatgtattct actgtaacaa tatgtggaag cttttttcaa ggttcaaagt aaaagcactg 8520
tacactaaag cttcaatatc taaaatccca cctccgtcta aaacctaatc agcagattcc 8580
taaaacaaat tcatctttac cttgcatgac atcatccatt gcagcataat ctgcaattgg 8640
ttcatcagcc tagaaaacaa atgaagacaa ttcaaaacca caagggagag ggagtctgaa 8700
atttgaagta tggcccatga ttcaactact gatattgcta taagacacaa acacactgtc 8760
cagtagataa ctcagtttca gccacagcca gcagcgtcca ggtttaacag cagatgccct 8820
gctggctatg ggtctagagt caacactgca gaagtggtat actgtgtgtg tgaagaggaa 8880
aggcaggggg gactattttc ccattcttaa agacaccttt agacatggaa atgtttagac 8940
accctggggt tactaaagac tgattaaacc aatgtgagct aagatactcg tagtggcagt 9000
gaggggtaca aataaaaagt tatactggtc ctctcagaat accaattagg ttaaaattat 9060
acttttgtcc cacttcacca gcaagaacaa gatacccatt tcctttttag gaggaagctt 9120
atgatgtctg agcttatgat aaggttagct gcaaggataa tgaagccaat gaccagtaca 9180
gactctagct gcccatgtga agtacaaacc gttcaacaat acaggctgtt ttaggacttt 9240
agacaggatc attaggatct agcaactcaa tgtgttttca aaaccatttc acagaaccta 9300
tacttccagg aaatgcagaa tgttaaacag agggaggggt taggtggtgg gatgaggggt 9360
gtgtgtgcat ggatggggta gatatgggtc tgcctcatca ttccagggcc taactttatc 9420
acaccagaac gggggctcca aggtttgaaa agcatacatt tcacagttca aaataaaaaa 9480
cctgaacaat gattctacca catgatgtgg tggtattcgg cacagtaggg attcttttgg 9540
ccaagaagaa acaaaagagg caatgggaag cgactaagtt aggcccttag ggagggtaga 9600
attgggcaaa tgaggctggt tcaatgactt ttctttcttt ctttttgaga cggagtctcc 9660
ctctgttgcc caggctggag tgcagtggcg caatctcggc tcactgcaac ttccacctcc 9720
cgagttcacg ccattctcct gtctcagcct cccgagtagc tgggatcaca ggtgcccacc 9780
accacgcttg gccaattttc ttgtatattt agtagagatg gggtttcacc atgctggcca 9840
cgctggtctt gaactcctga cctcatgatc cacccacctc aacctcccaa agtgttagga 9900
ttacaggggt gagccactgc gcccagtgaa agtaggggct tctaagacac tgtcaaagaa 9960
aagtcactga ggcctggcgc agtggctcac acctgtaatc ccagcacttt gggaggtgag 10020
gcgggcagat cacctgaggt caggagtttg agaccagctt ggccaacacg gtgaaaccct 10080
gtctctacta aaaatacaaa aaattggccg ggtgtggtgg cacacgcctg taatcccaga 10140
tactcgggag gccgcggcag gagaactgct tgaatctggg aggtggaggt tgcagtgagc 10200
cgagattgtg ccactgcact ccagcctggg caacacagcg agactccatc tcaaaaaaaa 10260
aaaaaaaaaa aagaagaagc ccctactttc tacatctact aaatccaaaa ccaatttcca 10320
tgccttggac agaatcccat taagtcgtgt attttgactg ttgtgacaga accttgtgtt 10380
ttacccttgt ttcctagctt ggctggctag tccttttgaa ccaaaaggaa aagaggagat 10440
actttaatac tatgacgtat ggttaagtaa ttctgctgaa ccggaagtta gggaaaaagt 10500
tacagaggag gctgaatcta cttttaacta agaaaaacta tgaaaatctc agcagagata 10560
gattttaaag tataaaataa gttactattt gcattggtca caagtctatc ttctacccat 10620
tttttgcttt ttttttttgt gggggcagca tttcaaatta agttgcagac atcagtatca 10680
ttagtgtggt tttaagaaca gatccatcta gtccaaaaaa aggaaaaaaa aaaaagcggg 10740
gggcgggggg ttggagggca ttggggaggg gacaccacag aaactttgtg acctgagacc 10800
agatcactca gcttgcccct ttggaatgac agtcaatcct cagtgctcag agggccacaa 10860
cccaatatca ctcccttcct cccagtctga ggggaatgaa aactagatct gtatctggag 10920
aagaatgggg gcccttgtga cagaaaatca aatgggaaaa atcaggcgtg gagcttagca 10980
gttgggtgag tgggatttat accactgccc tgccctacca gggaacagga aagtaatgat 11040
gtaccctgat cccacaaagg catagaaact gatctaggtg atccaggaaa ggccaaggaa 11100
agccttcact ttcaccttct cagggtacca gcagttgctg atgctgtggc gtaacatcac 11160
ctactataac acacaagaac aagatagatg atgtcctgac ctcctctaag tctcctgggg 11220
ctcagccaga gttgggctga gctgcaaaaa cccacagcag tcatttatca ctaccctctg 11280
ctaaagaccc aaggcatcct ttaaccacca tttcacacag tttacacata gttatgtaac 11340
atgtaaaacc ttgagttctt cagctaagga gctgtttact taccttcaat aaaatgacag 11400
attcaggaat gacgccaagg gtgcctaggg tggcacagtc atcacttaaa atctttccat 11460
caattgacaa attctggtca aaaggagcaa ctgaaaatgc atgcatgatc tgtgccaata 11520
taaaagagag aaagtccgta taatgcaaaa tactaagact tataccctat ttaaataaat 11580
tatgcatgga ttcttaaaaa aaaaaaaaag gcttcagagt acaaaaccac tattgtttac 11640
agtcagccta cttgttatac tcctactgag gctatcgtcc ctatatatcc gggaacatcc 11700
ttaagaggtc tggtagagta ttaggaaaca attacacata tagatgcgtt tgttccttac 11760
cttaccagct tcccaaggat ggaggtgtgg ggaaataaaa tgaataaaaa gtggggctgg 11820
gctgatggct attctgaggc ttgggcaagg tcatcactgt cacctcatct ttcccaggcc 11880
ccatatcctt tcatcaacaa gtcaagtcca aattctttct tttttctttt tctttttttt 11940
ttgttgttgt tgagacaggg tctcactctg tcacccaggc tggagtgcag tggcgcgatc 12000
atggctcatt gcagccttga actcccaggc tcaagggatc ctcccaccta aggcttctga 12060
gtggctgaga ctacagatgt gtgctaccat gtctggcgga ttttttattt tttatttttg 12120
tagacatgag gtcttgctat gttgcccagg ctggtctcga attcttagac tcaagcaatc 12180
ctcccagctt agcctcccga agtgcagaga ttacaggcat gagccactgc atctggccca 12240
aaattctttc ttaaaaccat ctttaaattc tctcttttgt tcttattcct ttagcaaatg 12300
gcctggggta tgtaattcag cctttggaac tgtcacatat tcttagactg agttttgtct 12360
ctaggaagca aaatatgaat ttctgaaggg tagggaccat atgccccacc ccagttctgg 12420
ccaagtgtta aaaattaaat acagccgggt gcagtggctc tcgcctgtaa tcccaacact 12480
ttgggaggcc gaggtggacg gatcacctca cgtcaggagt tcgagaccag cctgaccaac 12540
atggtgaaac cctgtctcca ctaaaaatac aaaattagct gagtatggtg gcacatgcct 12600
gtaatctcag ctactcggga ggctgaggcc agagaattgc ttgaacccag gagatggagg 12660
ttgtggtgag ctgagaccac gccattgcac tccagcctat acaacaagag cgaaactccc 12720
atctccaaaa aaaaaaaaaa aaaaaaaatt aaatactttc cagatgagtg tggtggctca 12780
tgcttgtaat accagcactt tgagaggctg aggcaggtgg atcacctgag gtcaggagtt 12840
caagaccagc ctggccatca tggcaaaacc ctatctctac taaaaataca aaaatttagc 12900
tgggaatagt gccatgcacc tgtgatctta gctacttggg aggctgaggg aggagaatca 12960
cttgaaccca ggaagcagaa gttgcagtaa gccgagattg cgccactgca ctccagtctg 13020
ggcgaaagag caagacacta tctcaaaaat aaatcataca tacattccaa aatactggta 13080
tacataatat ttaaatgttt ttacaaattc agaaaggttt gttttttaaa ttttatcatt 13140
tctgggtcat gtttacctct ggagggcaag aagaagttgg gctcagacag gcaaacacag 13200
gtaaccttca atgacactgt tttaattctt aactcggtag acaagttcaa gaatattcat 13260
attagtatgc tttttaactt acccataaaa tgcatgctat tacatgtatc ttatattaca 13320
ccaacaccca tgatgtcatg ggaaaaccat tctgcccttt cctgcactct attctttgga 13380
tgtggaaaga caaaacgagc ctcacaaatc aaccttgaac tgtgtgtgta acagggccca 13440
agagcttgac aggccagtgt gatggggacc agaaaagtga ttttaataat cgcaccaaag 13500
acaaataaga acaaggataa cagcactggc ctcctcccta actgctggga cagaatctta 13560
cctggatttt tcaaaagaac atcagcgcct gaaaagcagg cagggatgga ctagccagag 13620
atctgtggct agcaatgaaa agtgcactgg catcatcaat ggtcttcatg aagcaataag 13680
caggagtact gacaggacag ttctatccaa gccagctcag catgcaaaca tcaagcagag 13740
gcatatccag ccctacacca gcaaatgttc cggaaccatg aagattgagc agagctacgg 13800
tggatgtgtg tgatgctaac ttaacatgga taatgtcaca gctgctggac tgtaaaaatg 13860
cttgttcatg cccctaaatg ctaagtgttt ttgtactacc ctatgaaact ggacaaacag 13920
caaatacctc tagacacaag tgccacaact aaggggctga cgttcacaca ttatattctg 13980
agaacggaca agggcactga gatgctgtca acaactaatg aagcatttaa taagaagcta 14040
ccgtgtgtca agtactgttt taggtgttga taatataaaa gtgaataatc ccgccctaga 14100
ggggtttcca ggagtgaggt caaaacaaag ttgtgaggat ggtagcagaa ggtatgtgca 14160
ggatctagcg agcacagggg gacagtcagt tccatgaaag gggccaagac aggtttcaca 14220
gaagggtcaa tatgaaagat gaacacacgc ttctagagag aagatggaac aggccaacca 14280
aggcagggag gcctacggta aaataatcct taaactctaa gtgctaggag aatgcttcag 14340
tataaagaac acgatagagg tctgcttaac aagtagatgt ggcattcctg gtctatggaa 14400
cttaacagga accatgaaaa ccctgttgct atcagggagt ggctctcctc tgcttgcgat 14460
gctgtgtggg gctgaaaaaa gaaaatatag aagcgatcgc ctcagctgcc agccatttca 14520
cttctgtgcc aaaatattct actttctcag gcaggcaata ccacccaccc actaaagatc 14580
tatctttggg aaaatgaaat aatacaacta aacactgcac atcttttgag aaaggaaatg 14640
aacaaattgt acttcattaa cctcatggga tcaaaggtgg atgaattact gattagacac 14700
agcaagcttt gtaatgtttc aagcaaacct tacaaactct gatgctatcc acactgccag 14760
gcaaataggc tcacatctag ttgaagcttc acaagctccc accactatgt agtgagggga 14820
aagaccttct actgcctttt ctttgactct gtttggcccg cagtggtccc tgaagcaaga 14880
gtgggagatg agacagacat tcaggaagag cacctctggg ggctgtgtga acagctgcca 14940
tcttctagca gctcattcgg gcaggtacat gctctcagat ggaagggtta tttctgctga 15000
cttctggttt attcttcaaa aattgtagtc cataataaaa gcagcacagg cttttaaaaa 15060
tgtctttagg cacaggggct ctttctgtaa tttaaaggtt ttgaatgttc gaggtttccc 15120
aatgacaggc agaaagccag tgatagaaac aaggtttctt agatgtaaaa ggtacaataa 15180
cagagtaaag atattatgcc aacacactta ttttcagagc catgggttca accaagggaa 15240
atactgttgt caggacaatc tggaatacat aacaccctca aaggaaggcc tgtacttttg 15300
cctcaattac aatgataaat atcagcaaca agaaaaatgt gtaaccagta aactatgcca 15360
cataaaagta gcaaaggagg aaatttggtc aactttttgg atatctatca gtgactgaaa 15420
cagattaggg gccagaattt tttatggaca tcttgaattt atcagttcct tctgcctagg 15480
gtttgagatt taccactgga atgcttattt atagtacttc agtattgata ccaagaaata 15540
acagtatcat gaaaccattt cataatgcct gcactacagc cgtggaactg atttgtaaag 15600
caatgcatgc tttgaggggg atggagagga catatctaaa ataaatctat ataacaattt 15660
ggaaaacatc aaggtaaaga taattttaaa actctatcaa ggccgggcgc ggtggctcac 15720
gcctgtaatc tcagcacttt gggaggctga ggcgggtgga aaacgaggta aggagttcaa 15780
gaccagcctg gccaagatgg tgaaaccctg tctctactaa aaatacaaaa attagctggg 15840
tgtggtggca cgcacctgta atcccagcta ctcaggaggc tgaggcagag aactgcttga 15900
acccggtagg cggaggttgc agtgagccaa gatggcacca ctgcactcca gcctgggtga 15960
cagagtgagg ctctgtctca ccaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaccc 16020
cctctatcta tcaaatagat ttatctgcca ccaaaaatac tgtgacagcc tagtgaataa 16080
gcaatcacta atcgctaata ataagctgcc ttttatctcc cattaaattt cacagcagtt 16140
cctggtaaca gcctccaata cctattaagt ggtcaaagaa aagcatacag cacaataaag 16200
tgagagaaca gttatcctgg cacaacctca acatgtgaca aattaagtgg ttcccagcgt 16260
ttctcattat tggaaagcta ttgcagaacc agcccaagtt tccagaaccc aaaattcact 16320
ttcatcttca caaaaagatt tttggctatt ttgaaaactt taagtcttct ggaaaaaaac 16380
acagatacat acatatatgt aaatacaggt ggaaagcagg aattcataaa ggccctttta 16440
agtccagagc aaacttgaac aaatgtttcc ctcacctgaa ttttcaattc ttttaacgtc 16500
tgattagcag aaacgagaag tgctttctca ccacgaactt ttctatgtcg catacttcgg 16560
cgaataactt gcttttgata ggctatataa ttttgatggg atatcttttg ccgctttgtt 16620
ccaccattgc tctataatga agattggaaa tgaagaaagc actgaaatta accacaatgt 16680
gacccttgct catgaagttt ttcaggtaaa caaaagctgt ttccttattg gtcccttaac 16740
tatttgaaat tcaatgtaaa caatgagtag aaactaacga gactttctta gcaggctcac 16800
ataaaattga taaaagaaaa taatgagtaa tacacacctc taagtgcatg taagcagttt 16860
aaatgtttgt tacaagagac atttaaggtt tggtgaggag gctcccacct ataatcccag 16920
gagttcaaga ccagcctagg caacatatta agacccatct caaccaaaaa ttagccaggc 16980
gtggtggcat gagcctgtag tcccagctac ttggaggctg aggcaggagg atcatttgag 17040
cccagtggtt ccaggctgca gtgagctaca atcgcaccac tggactccag tctgctgaca 17100
gagtgagact ctgtctcttt tataaaaaag accttacatc agaaaaacat aataaactga 17160
aaatcttgag gattacaaaa cttagttcat gaacaacctg aattttaaac attttcttct 17220
cttcttgaga atgacatgga aactaagtat aaactgttgt gaatttaaaa ataaaatatg 17280
gaacattaat aaaaaaaaat caaacttagt ttgactaaaa acaagacttt accacttgtc 17340
ctaatggcaa aatatacaga ctcactcata aaatattctt gcaaaaatgt tatactggaa 17400
tgtaatcaaa catttacgcc cacctttcaa tttacagaaa ttggaatata ggggatatat 17460
aaataaatta aaataagtaa cataaagaag caatcagcca aatacagaac atggaacaat 17520
ctaaaagaaa tcaaactggt ccaagttcaa tgtcaagaag gcaaagagcc tggcatggtg 17580
gctcacgcct gtaatcccaa cactctggga ggccgaagtg ggcagatcac ctgaggtcag 17640
gagttcgaga ccagcctgac taaaatggag aaacccccct ctctactaaa aatgcaaaat 17700
tagccgggca tggtggctca tgcctgtaat cccagctact agggggccaa ggcaggagaa 17760
ctgcttgaac ctgggaggcg gaggctgcgg tgagccgaga ttgcgccact gcactccagc 17820
ctgggcaaca agagcgaaac tctgtctcaa aaagagaaga agaagggaaa gaaagcgggt 17880
gcggagacag agtaactgtt ccaaattcta agtctaaagt gatacaaaca acacatatcc 17940
taattacata ctgatttgag aggaaaaaac tgttcaagac atatctgagt atgggtatta 18000
gaggacatta gggagttttc gttagttttc ttatttatga gcacattatt agtattaggt 18060
aggacactgt ctttattttt agaggggaaa tgtcatgatg gccatgacta cctaaaggtg 18120
ctgtaaaaag gatgcccctg ggtgtgcatg atacatgcgg taccagtcaa gaaaaaaata 18180
gatgaggacc aaatgtcctc tacagtactc ctataaatcc ctcatcaaga ggttaatgat 18240
cagaggttaa tgatcaagat tcttttgctt tttgtaccaa aggtggtggt ggtggccggt 18300
gggggcggtg ggggatgggg ggtgagtgag aggcgcaggg gagattcttc tgctaaccag 18360
gccagggaat aaaagaagca ggatttttaa gaaaatcttt tcccctggtt taattaaatc 18420
tggatgaggt aacctcaagg ccctggctct ggtttccaca gtcgtcactg aatgtcagcc 18480
gtgtataagc aaagtggttt aacggtcatt atagacacag atgccacata ctcattactc 18540
atgggctcca cagtttacaa agcagaaggt gatcaagacc caaacacaga agagcatttg 18600
ttcagggtgc cgaccactgg cgagacactg cctgaggata gtttagctct agccctgaat 18660
ctacataggc aactgagtga ttctaagatt cacgagaaaa agttaagtgc acatgtgagt 18720
taaaaagaaa aaaaaaaaat gaaacccgat gaaacatttt tctcagtctc gactgttgaa 18780
agaaaaggtc aggccaggcg tggtggctca tgcctgtaat cccagcactt tgggaggcca 18840
aggtgggcgg atcacaaggt caggagattg agaccatcct ggctaacatg gtgaaacccc 18900
gtctctacta aaaatacaaa aaattagccg ggcttggtgg tgggcgcctg tagtcccagc 18960
tacttgggag gctgaggcag gagaatggcg tgaacccggg aggcagagct tgcagtgagc 19020
tgagattgca ccactgcact ccagcctggg caacagggca agactccatc tcaaaaaaaa 19080
aaaaaaagaa agaaaagaaa aggtcaaatt gaacccaaat tctacaatca ggaatataaa 19140
gaaaaataac tacatcaaca tataatttta ttttagaagt acaaaacaca accaaaaacc 19200
aaaaccctga gcatcaagca agacagattt tttaataact ctgattttaa atggatctaa 19260
aggcttttcc tggaattatt tctttcttaa tctggagaat ttaaatccaa cttaactgac 19320
aaaaaaaccc agcccactgg ttttagaagg ctttcaatta cctaagtgat acccaatacc 19380
gagtatatta ttaacctaaa tttttagatg aagtcaaagg agttgggttg atctagctta 19440
gagaaaagag gaaaagggat ttgtttatct ccactaagga caagcagaaa tgcatcattt 19500
tttattacag ggatttaaag cagcaattac agaagctatc tttgtactga gatatgtgat 19560
gaggagggtg acattttgaa aatgctgaac atttttcagg gactatctat tcttttccaa 19620
agaggaaggt tacacttgag attttttgtg agccaaaaat tttttgtgag aaagcaaaat 19680
gtaaaacatt ttagagtatt acaatatcca aagaaggaaa aggaagacag aagaaaatta 19740
taaagtataa aaaataatta cagtataaaa agcaatgttc cccaacattc tctatcatat 19800
ttataaacgt gaaatctgtt gtcatccaca actaaggaga gtgattccac atacactttg 19860
aaaaaattgc tgtggtcatg accacaatga ataaaactag accaccaaaa aaaagttagc 19920
tttctaaaat ctaaatcact tgaaaatgta gatagtttct aaataactct tagggtgaaa 19980
agcaaagctt aaaataacaa actaaagaca gtaagaacat tgtgtcaagt ttaacaaact 20040
aatttacaaa gttaaccaga gaacagataa ttagtgacag caggcaataa aagatttgat 20100
tcccccatcc tggatatcac ggtgaaaccc cgtctctact aaaaaataca aaaaattagc 20160
tgggcgtggt ggcgggcgcc tgtagtcccc gttactgggg agcctgaggc aggagaatgg 20220
cttgaacctc ggaggcggag cttgcagtga gccgagatgg caccactgca ctccagcctg 20280
gacgacagag caatacttgg tctcaaaata aaaaaatttg attcccaact gattattaag 20340
ccatactacc aagtgataat aactaaaaca tacggtactg ccagccaaac agacaaaaga 20400
gaatggagtc ctgaatcggg atggatatgt acacccatac acccaaatgc atgtacatgc 20460
acagagtctt gctctgtcgc ccaagctgga gtgcagtggc acaatctcgg ctcactgcaa 20520
cctccacctc ccaggttgaa gcaattctca tacctcagcc tccccagtac ctgggattac 20580
aggcccacac caccacacct aatttttttt tttttttttt ttttttgagg ctgagtcttg 20640
ctctgccgcc caggctggag tgcagtggcg agatcacggc tcaccgcaag ctccgcctcc 20700
tgggttcacg ccattctcct gcctcagcct ctcgagtagc tgggactaca ggtgcccgcc 20760
accacgcccg gctaattttt tgtattttta gtagagacag ggtttcactg tgttagccag 20820
gatggtctca atctcctgac ctcgtgatct gcccgcctca gcctcccaaa gtgctggaat 20880
tacaggcatg agccaccgtg cctggcctaa tttttgtatt tttatttatt tatttatttt 20940
tgagacggag tctcgctctg tcacccaggc tggagtgcag tggcgtgatc tcagctcact 21000
gcaagttctg cctcctgggt tcatgccatt cttctgcctc agcctcctga gtagctggga 21060
ctacaagtgc ccgccaccac gcccggctaa ttttttttgt atttttagta gagacgggtt 21120
tcactatgtt ggccaggctg gtgtcgaact cttaacctca agtgatccac ccgcctcggc 21180
cttccaaaat gctggaatta caggcgtgag ccactgcgcc tggccacaca cacacacaca 21240
cacttttaat atatcaactg aaaagcacac aatcgagttt gcacaaatgt ggctcgaaag 21300
atggcttgta tagaccacag agatgtcccc gccacagaga tggggacatg aaaacagagt 21360
tgacaacagg gtaaagggcg gcagcaaagt catgtctgca aacgcttgtg gagacatatt 21420
agtagagtca actaatatgt ctccacaagc gtttgcagac atgactttgc tgcccttctt 21480
taccctgttc cttatgccaa ggagcacaag atgtatatat gcacacagag tttaataagg 21540
gcatcactta ctatagaaaa atatcccctt taaactgaaa acctgcattc tcatcaagtg 21600
tacagatttg gttagcactg aagcaaaggg ccctccagtg ttgactgact gaaatacaga 21660
ctgggaagga caacttaaag agtggctgat cactgtcaca aactgcatga ttttgcttct 21720
tcacaggtgt tttgaggtta ttttatgagc gccaataagc cacggaaaac aaatgctgac 21780
atccctttac accggttggg aaaccacaag taacatttat tttgggcaca ccaagattca 21840
aatcaagacg gcttttcaga ctctctcaat caatgttaaa aatgaagtaa cagtatcaac 21900
atgcagacag gccaacaagc ccagatacct ctgccctgtc acagatattg cagatggcta 21960
ttgtaacact ttcattcttt cagggagaac accatccaca atttcactac actattttag 22020
tagtaaagaa agaaaacaaa catctcatct gttaaaaata aaactttgag tagaaaatcc 22080
atgagtttaa agtacaaaat atcctccaat gtgggggtct gactttttga gaagctgaaa 22140
cttatctcca cctacatcaa ccatattccc acgatttcct gttctcaaaa gacaatttat 22200
gggccggatg cggtggctca cgcctataat cccagcactt tggaaggcca aggcgggagg 22260
atcatgacat caggagttca agaccagcct aggtgaaacc ccgtctccat taaagataca 22320
aaaaattagc caggagtggt ggcgcatgcc tgtaatccca gctacttggg aggctgaggc 22380
aggagaatca cttgaacctg ggaggtggag gttgcagcga gccgagattg tgccactgta 22440
ctccagcctg gttgacaagg ctaggatcca tctcaaaaaa aaaaaaaaaa aaaaggccgg 22500
gtgcggtggc tcctgcctgt aatctcagca ctttgggagg ctgcggtggg cggatcacga 22560
ggtcaggagt tcgagaccag cctggccaac acagtgaaac cccgtctcta ctaaaaatat 22620
aaaaaattag ccgggtgtgg tggtgggcgc ctataatccc agctacttag gaggctgggg 22680
caggagaatc atttaaaccc aggaggcgga cattgtggtg agctgagata gtgccattgc 22740
actccagcac aggcaacagt gcgagactcc atctcaaaaa aaaaaaaaaa agaaaaaaaa 22800
agaaccaata tcccatacag ggtacagaga catggccagg ggcttcgagt ggctgctcta 22860
taagaacagc agaaagtata acaatgaaaa gcagcttcaa cacatacttg attaaaatct 22920
ggatcttttt ctccatctgg tttagcttct tccttgtcct cctctgtttc agaactactc 22980
acattcagtt ccggagccga atccttcatc acctgaatgt gccaggacaa caaagagaag 23040
taggtcagac cctaggaagg caggctatgg aggatgtggg ggctgggacc ggcaaccttt 23100
atcaagacga ggaacacctt tatcatggtg ggattataga ctggagagtg gatcaagaat 23160
caagccttca cggttttcta tgctctttta acatgttagt tttttaccct atgacttatt 23220
cttgtagtat ttaatgtgct caccatacat ttaagaggtc tctgcagagc agttattatt 23280
atcagtcttg tacaatgatg ttattttgca gaagttcgaa ggtgcttgac accttcccga 23340
gcacactgat tgccaagcct tttcaagttc tcaaactatt caagtggcag gagttacatg 23400
ctctttaaga attgagaaaa cgaaagatgg aagaagcgct ctcttgcaaa cactatgaaa 23460
tactcttatt aaactgaata atgaaactac atctaaattg gataatattt tataccagag 23520
aacaaaagat ttaagaaaat tttacaggga gaaacagaga catttatact cattaacttc 23580
attttctcgg caaattagga aatgaaggcc ttagtttatt tagcttgtaa agcagaaccc 23640
ttggcctcca gggcataatt ataagttacc cttctaaaaa atgtgtttgg aaacaagcat 23700
caaataaaat gtattccatt ttgtctttaa tcccagaaag catggaatta aataaattaa 23760
taagatatct agagatatgg gtcaggatct acccaagagc catccctaat ataataaaaa 23820
tgcttggaaa tccaatccaa gcaagtatta acacctccac ttcccaaaca tatccaatca 23880
atttcaccta tccttgcagg tcaatggaag aggctctaac tgacctctct tatttctgtt 23940
atgccctcac agcaattcca aacactatag ccagggtgat tttttttaaa ctataaatca 24000
gatcatatca tgaccttgct tgaaactctc caggggctta tatctacact gggaataaac 24060
ccaaatcctt ggtatgatgt ataaaacctg atagtgtatg gtcgttcatt ccatatcatg 24120
atcccttctt ggaataaatt tcattctaga ccagcaatag ccactagggt agccattagc 24180
cacatgtagc tatttaattt taaatcaact aaaactaaat tcctcagtca cgctagccac 24240
atcgaatgct ccacagccac acatggccag tgactactgc agtgcgcagc acagatacag 24300
aacctagaac ctgtctatca ccacaggaag ctctattgga cagcactgtt ctaggtgcaa 24360
tggttttcac tctgttgcat aagcacatta ggcttatcct tttgaccttt gtttcctttg 24420
tctggaaaac acttcccagg ctgcatccct gacagtgagg gcttgggtaa aaacaacttc 24480
tccaagacgc ctctcctgtc tactccctgt ctcacactaa cctccacttg accctgctaa 24540
agttccttca aaacaatcat ttctgtgtga aatcatatga atttatactt tattcctgat 24600
cttcctcact aggtgcctat aattttgaga gaaggtatta tacctgcctt ctttatcact 24660
gtatccccag cacctggacc attcctggaa cacagctgac attcagtaaa tatctatgca 24720
tcaattaata acaaactaaa ttctcatata atcacataac tgttcatttt caattattgt 24780
ccaatttcaa ttctgatgcc aaacagctct gaaggaacaa aaatgcagtc ctaggcagac 24840
cctcagtgca aatacaacag caaatcaagc caaagagcac gcttgatcat tactagtcat 24900
tgccacaaga gggaccagta cctttttatt atccacaact ttatggacat agatggtggc 24960
ttgagtgtat tcacgcaggt ccctctgctg ctgacacaat aagccttctc tgcattctgg 25020
acagagttct ttgggggaaa aaaaaaaagg gaaaacagaa gtggctgagg aatcattgtt 25080
aaagaatcaa agatctaaaa acatatgtca aagttactag tgaatattca ttaaactctt 25140
agtaacattt tctttttttg agacaaggtt ttgctgtgtc acccaggctg gggtacagtg 25200
gtatgaacat agctcactgt agcctcaagc ttctgggctc aagccatgct cctgactcag 25260
cctctcagcg agtagctcaa gactacagat atgtgctaca tttttattat tttgtagaga 25320
gaaggtcttg ttatgttgct caggctggtc tgaaactcct ggccttaagc aatccttcca 25380
ccctagtctc tcaaagtatt aggattatag gtatgagcta gtgtgctggc ccaaactctt 25440
aataatattt tctattaacc actatattct attacatgca aatgataagg aaatccattt 25500
actgtccata aataaacgta caaataatgg gatgattata atgagagttt ccacctaggg 25560
agttgggacc gccgcatgat ctttaacttt aagcagacaa cactgacaca ccctttcttc 25620
ttaaaatgtc agctcttaac tatagaaacc gaaagcaata tgaaaactta ctgggctcag 25680
aaatatactg tgtttctgaa gggtttacat ctcccacttc aattctcgtg attttaatta 25740
catgatccac aacaaagagc ttttgtatca tttgccactc actgggccat atgagagcta 25800
tactgtgcaa aaaaaaaaca caacatgcct taagacacat ggaaattaag agaattaaca 25860
taatccatta gtctgctaaa ccaaaaccat taacactaac atttaatcca aaggaattag 25920
agagaaaaga tacgtatcat caacaaagaa tagtttttca tacaaaggaa tgttaccaca 25980
gcagcgaaac taaatggact gaaattacat gaatcaacat ggttagatct caaaaacata 26040
attgagtaaa ataagttagt tgcagaagta taaatacagt atggtgccat ttatataaaa 26100
agttttaaat atgcaagaca ttatgtgcgt gcattttttt tttttacaga atactttctg 26160
agacagataa actctaaatt cagtacagtg gttagtgtga gaggaagggt gggagaaaga 26220
gaagtagcaa cagaaggata agcactgtgg ggcctttaat catatttgaa ccatttaact 26280
tttaaactga atggtaacac acatttgctt actggtgtat tttcctggaa gtctgacatt 26340
tgcaataaca acgacaggaa gaaagggagg gaggaaagag aagagagatg cacagcgaga 26400
gtgagagagc aacagggaag gcgggatgca gagagggagg gagagaaaga ggagggagaa 26460
aatgtagaga atatataaac tttgaactcc cttaaatgat gttaaagtac tgaaatatga 26520
ataataaaac tctagcttaa ccccaagggc atttttattt atgtgttcca atttcctttt 26580
cctgattttc tgacaatgtt ggaagcattc taccttctcg tatatcacga tttttggtaa 26640
aatcgggaga aattcacaga tgaacacctc tggaagtact tgaagcatgg aataaaattt 26700
gggttctaag accctagaat tccagatgac cagtgcagtg gctttgctct gccaccctgc 26760
tagcctcctc ctttaattgt ctgaagcctg gccatggcag aacaaaacct ataaccaaga 26820
ccatgttgat tctgtgattc tggaaaagag gtctcagcac tggtcaccag cagcggggga 26880
agagaaaggg tggctgtgtt gtcttcaaga gggacaagga aagagcaaaa agacaaatag 26940
cctcgggcag cctcttgtct ttcctggaga agcagtcttc ttctctttta aaaggggaaa 27000
aaaaaacccc acaattcagc aaaggactaa attcttaaaa cagactatgt cagatgagaa 27060
atttcctaaa catattttat taatcatcaa aaagagaaaa gaagaaaaaa aaatcacatg 27120
aagagaagga actcacagtt tagaatcttc tttggtcatg gaagcaaatg taaacatgag 27180
gcccccgtgg ggacacaaaa gagcactgtt cccaactgat gacacagggc tgcatcttgt 27240
aggctttcta ctcaaatgag acaaggagga gaaatatacc taattactgc atgacgaaag 27300
agaagatttt aaaataatta tttcaaaatc agagatatat ttaagaaaat attagtaatt 27360
caatgtgttt cttaggctta ttcatttaat taatagaaaa gaaagctttc agtgtatgct 27420
ggtgaaagta accatgaagg aagggtacaa caaacagaat ccacgatatc ttaaaaaata 27480
ccagagtcaa ccaaatcagt aacaataaag gaaataaaac atattttgtt tctacctaac 27540
aaatttccgc cactcttcta caaagaactg agacacgatg tagaggacat ccgtatccta 27600
gaacacaaaa atcacaaaac agtatccgtc aattcaccgc ctgcttaaca caaattcctt 27660
ataatatact ttggttgtcc ttattcaagt tttataaata aaatgaaaac acagtcctct 27720
accaaaaaat agcaggctgg agtaaatccc ctggttagat aactaaacaa atgagaatat 27780
gagaagttct gggttgttct gaaatagctc actgggaatt tggcaagggc tttaaaaaga 27840
aaagatgcat tctttctttt gtgggaatca ttatacctct ggccagttac tgagacacgg 27900
tctgttttta tcctggaaca aatttgggag agaagtcttt tgctcgtttg caatcatctt 27960
atgtaaggct tcattttctt ccccttctct ttctaaaatc tgaaagagaa tgaagcaatc 28020
aactgtctcc tgctgacagc acatgacctg cctcctccct acacccccgt cagaagtaca 28080
gtgttaattc ccctgggaag tcaacccagg gaggtggcat gccatttccc cagatgtcag 28140
tagcgttcag taccttgcac tgtgaacagc actctttgta acttggaaac tcaggagcct 28200
ttggaaagta ctgctgcagt ttgctccaag cctctttaga aacaagcctt ctttcatttt 28260
cagatatgca taactcacct gagtttaaaa aaatatattt ggaaaaaaaa aaaacagctg 28320
aaaaaaagtc attatctatt tcctatttct taaacttaag aaaaatccac aggtacgctt 28380
ttcttgcttt gctaaagttt ggtatttcta gctctctttt cttgttttca aaaacttctg 28440
aatttccgat ttcattttaa ttctaaagga ggtagccatt aacctcaatt ttacgtcctt 28500
aatctaggtc tgtgattgaa aaaaaaatca tgagataaaa acaaacgtac aaagctaaaa 28560
ccgtgcattt tctttctcct tgcaaggaag gaagtagtca aaaatgggat tccaggagtc 28620
ctgggacctc tgtgccatgg caagcgctgc ttaacaaaat tacatctact cccacactca 28680
aaggttatca tttcctgcag actttattgc ctcccatttg actaatcttg aaatcacact 28740
gcattaaaat aatattttgt aagctgtgtc cagccatcac aagaccactg ccttaagtta 28800
tcaattcaaa gttatcaatt caaacagaag ataaagcaat ctactgctca atctgaaaac 28860
catctccagt caagcaccaa cttctttgct atttgcaatt tattttgaag atccccttca 28920
atcttcaaaa atcccagaag atataaaaaa ataatactag tcaccgccac cctgccagga 28980
cctttctcct ctggctctac ttgtggttat acttactgtt gtttcagctg ttcccaagca 29040
gtaagttagt gaacttcact tatctaccca tatcggtcat tacccagaaa actatcttta 29100
aatttctaaa gtcatatgtt tgtttctgca cccattggca aggtacctac agatttatta 29160
agagtaataa agccatgagc tttctaaata catactacac tttccataat aaatgaattt 29220
agaaagatga atataaccag gcagagtaca gctagtgagt aataaagctg ggatacgaaa 29280
ccaggtctat aggccaggca cagaggcttg ctcctgtaat ccccagcact ttcggaggct 29340
gaagcaggtg gatcacttgt caggagtttg agaccagcct ggccaacatg atgaaaccct 29400
gcgtctacta aaaataccaa catcagccag gtatggtggt gcttgcctgt agtcccagct 29460
actccagagg ctgaggcaag aggactcctt gagcctagga ggcagaggtg gcagtgagcc 29520
aagataacca ccattgcact ctggcctggg caacagagag agacgccatc tcaaaaaaac 29580
aaaacaaaac aacacaaaac aaaacaaaca aaacaaaact aggtctgagg ctgggcttgg 29640
tggttcacac ttgtaagccc agcactttgg gaggctgagg ggagcagatc acgaggtcag 29700
gagtttgaaa ccagcctggc caacatggcg aaaccccgtc tctactcaaa atacaaaaat 29760
tagccaggtg tgtggcaggc acctgtaatc tcagctactc aggaggctga ggcagaagaa 29820
tcgtttgaat gcaagaggca gaggttgcag tgagccaaga ttgtgccatt ccactccagc 29880
ctgggcgagg agcaagactc tgtctcaaaa aacaaaaaca aacaaacaaa caaacaaaca 29940
aacccaggtc tatagctcat tcgaacccca taatatattt taaaatttat ttatttattt 30000
aatagaaaac aggccggggg cagtggctca cgcctgtaat cccagcactt taggaggctg 30060
aggtgagtgg atcacaaggt caggagttca agaccagctt gaccaaaatg gtgaaaccct 30120
gtctctacta aaaatacaaa acaaattggc cgggagtggt ggtgtgcacc tgtaattgca 30180
gctacatggg aggctgaggc aggagaatcg cttgaacccg ggaggcagag gttgcagtga 30240
gccaagatcg caccattgta atccagcctg ggtgacagag caagactccg tctcaaaaaa 30300
aaaaaaaaaa aagaaagaaa agaaaagaaa agaaaagaaa acagagtctc attctgtccc 30360
ctgggctgga gtacagtggc acgatcatag ctcactgcag cctcgacctc ctgggctcaa 30420
gcgatcctcc tgccttagcc tcctgagtag tctggctaac aggcatgagc caccatgccc 30480
gcctaatatt ttattttgta gagagggagt ctctcgaact tctggtttta agcaaccgtc 30540
ctacctcagc ctccagaaat gctgggatta taagcatgag ccactatgcc tggtccctat 30600
aatttataat acctcagaat gcaacttaac ttctacccct cacctcttct ggatctttga 30660
ataatcccca aaagattatt ttgctttaac agacttgtta ccagagaaat ggggtcagaa 30720
tgtaaacatg tatttccttc tgggtgggct gttaatttaa atttcccgtg agtctatgaa 30780
aacttattct aacgtgccca tcctcagaca caattaggga atttattttt aaaaatgaaa 30840
gaaaaaggtt aattggatta tcaaacctta acttagtaag tccttatgtg aaatacaacg 30900
taaccataaa aaagattaag gtagatttcc atgacctgat ttggaaagaa ctccacggca 30960
actacaatat ttaaatggtt tcctttttat gctttaaaaa aaaaaaaaga gagcttcttt 31020
gtgtgtggta taaccccatg tggttatgag gaaacaataa tgggaatgca cacacaaact 31080
ttactattaa atgagcagag gagaccacag acactgtggg tgcacggctt cattctgatg 31140
tgggggtact tttaggtagt gactggcttt taagtgggat gagtgttttt catatgacaa 31200
ggaaagaaca acccaaattc atttctgaga tcagaataat attaaatagt cattttactg 31260
tagtctagtt ggtaataaaa atatatagtc cttcactcta cttgttagct gagtttctaa 31320
atataatttc ctattattct aataattact accatagtag ttgttaatat atcattaata 31380
ttaactatga atattaatac aattaattaa attaatgtaa tgaatgataa tgaagtaaat 31440
atacttgaat attgtctatg acctcaaaat agttaaataa atttgggttg ctcttttcac 31500
tgggacacat aaattgttag aaattaaact tgtatcctgc aatgaaacat gttatttctt 31560
aaattttaag agaaagccaa tcaactaaat ccattctatg agcaatacct cccaaaacaa 31620
gatcaaagca gtcaagagag attcaattca gtaaacataa ctagaatatc taaaactcaa 31680
agattctttg gtaaaaagag aaatctagtt aacaatgaat ttagatactg gataaatgac 31740
cctcaacccc tcaccctcaa tctagttcaa actgtatata atactttggg cctcaggaca 31800
tctcaagaag tactttcaaa ataacaaaac aaaacacagc ccatcgtcta agcaaactag 31860
gtgtaataaa caaggtaagc tataggaagg ttattcactt aaaggaataa aaagtaaaat 31920
gggtaagaaa gcttgatata tataatatct gtattataaa gcttgttata taatatctgc 31980
aacaaatact gaactctagg atagtaaatc ttccaatgga atataatcca atgactaatt 32040
cacacaaaac ctgtgataca ttaaatacat acaacacgtt agaaatatat aggggttttg 32100
ttataaaaat atgaaaattt aaatcaagga ctttccaggt taaaatgatg tttaaaactg 32160
catttacttt aagtgcctca tgaaacatca tcaaatcaca ataaagaatt aaaaaaaaaa 32220
aaacttttat ttttagagac aggatctcac tctgtcaccc aggctggagt gcagtggcgt 32280
gatcatagct cactgtaacc acaatctcct gggctcaagc aatgctcctg cctcagtttc 32340
ctgggcatct aggactacag ccgtgtgcca ctttgcctaa tttttatttt attttttaaa 32400
tagaggtggg gtctcactat gttgcccagg ctgctctcaa atgcctcagc ctcttgaagt 32460
gctgaggtta tagatgtgaa ccaccacacc aaaggaatta tttatatata tatataaaag 32520
acatacagtt ataatgatga agacaacaga ggcaacaaca gggataaaaa ttataagggt 32580
ttaaaagaag gttaatgaga cacaataaaa attaactcta agttggcgaa agtcaagaag 32640
tagccagatt tgctacactg cagtactgtc ccacagaccc aaaaactggg tcctcatgaa 32700
gtaaaggtag ggatttacaa aaaatgagag aagggatgga aagtctattt aagaagtatg 32760
tagttagatg ctcagtcccc ttctctgccc ttgagatcac tgccccctct agccacaaaa 32820
gactagatgc ttattctagg acaacaaaac ctaaggcccc tgaacagggg acacaaaaca 32880
cagagacaaa tgaagtgaca agctgagaca gggataatta aacctttcca ctcttcaatg 32940
cagggactcc taagtcctct tctttctaca gcttccgaag agcgacagca ggtctgaatt 33000
ttccaggcag gcaaataaaa gatacttacg gaaaaacctt agtggcccaa tagcagacag 33060
tgccattggg aatttcccag tgaaacaagc cagctggggc tccgaactag tgaagctcag 33120
tcaccaagcc cctccaaaac acacctggct tccacagagt gcctagcata ataaatgaac 33180
ccgtacaaca ttggggacaa agatcttaca agcctaccag aaactgaagt ggagaaaaat 33240
taccaagaaa caatggcttt ggacttctga atggtacgtc cagagcacta ccacaaaagt 33300
ctcttaaatt ttcacggaaa aaatatttcc aacagacaac taaataccta ggcaaaatta 33360
tccattcagt atggtgatcc tagacaggtg actcttgcct ctctgtgcct cagtttactt 33420
actcatcagt agaatggatg tgataatata ctgatagcac agagttgtta taagattaaa 33480
tgagttggat gggcatgatg gctgacgcct gtaatcccag cactttggga ggccaagaca 33540
ggcagatcaa ctgaggtcag gagttcgaga ccagtctggc caacatggca aaaccccata 33600
tctactaaaa atacaaaaat taactgggag tggtggcaca tgcctatagt tccagatact 33660
tgggaagctg aggcaggaga atcacttaaa cccagaaggt ggaggttgta gtgagccgag 33720
actgcaccat tgcgctccag cctgggcgac acagtgagac gccatctcaa aaaaaaccaa 33780
aacaaaatag ataaaatgag ttaatattta taaatgtgga aaactacagg caaatggtaa 33840
acattcaata attgcccact ataatcctcc tcttaccaac atcatcagca cacctccaga 33900
aagtggtttt aacagaaact taatgagtaa agtggatttc taagtaaggc tgggtatcct 33960
ataccagaaa cattttaccc tggacgcatg gtatgctggc agataacgta acacaaaaac 34020
aaaggtagaa aactatcctt tttttttttt ttttttgaga cagggtcttg ctctgttgcc 34080
taggctagaa tgcaggggtg ccatcttggc tcactgcaac ctccgcctcc tgggttcaag 34140
caattctcct gggtcagcct cccgagtagg tgggattaca ggcgtccacc atgacatcca 34200
gctaattttt gtatttttgt agagatgggg tttcaccatg ttggccaggc tggtctcaaa 34260
ctcctgacct caactgatcc gcctgcctca gcctcccaaa gtgctgggat tacaggcgtg 34320
agccaccaca cccagtcata ctatccttta aaatattaga gaacaaagta tggcatcaaa 34380
acactagagt tacagatcaa gacaacagcc taaaaaaata acccttgtat acaatttctt 34440
cctctctccc tcactccctt tctcattccc tccctccctc cctttctttc tttctctttc 34500
tcactctctc tttctttttt gttttgtttt gagacaaggt cttgcttggt cgcccaggct 34560
ggagtacagt ggcacgtgaa tatggctcac tgcagcctcg acctcctggg ctcaggtaac 34620
cctctcaatg tagcctttca tgtagctggg aaaactgatg catacgatca ccacccctgg 34680
ctaatttctt gatctttctg tagagatggg gtcttgccat gatgccaagg ctagtctcaa 34740
actcttggac tcaagtgatc ctcccacctt ggcttcccaa agtgctggga ttacaggtgt 34800
gaagccactg tgcccggcct cttatgtaca atttctgata ggctggggag tggagtatgt 34860
gtcctgaagc aacattcggc tttgccatgc tttgtattca aaactgtcag tactgaaatg 34920
acatgataag aggtgggaag gcagagcaaa ggtcagtgag ctaaggagca cgagggcaat 34980
ctaagttcca gcactgtttc aagtggtagc accaagcatg acacagtatt ttgccacaga 35040
tgcttcaact ctcaatatgg aggcaccaat cctatgtcca catctatgct gtgaaggtta 35100
gaaaaggtga tatgagagta tcactggaaa aatacactcc ttttggctat tcacccaaac 35160
ttccttcccc tgtttatttc ctcgtgctat tcagcactca cgaggtcaac tcatcttctc 35220
ctgctgtgca cctgtagtgt aaaagaccaa ccagtagaca gatagggtga tacgatggaa 35280
agaacagagg aacttgggac tcacagagac caagacccaa acacacaccc caggatggcc 35340
ccttcctagt tgtgtggcct gtaaatggga atgccactca cttcgcaagc taaagtgcag 35400
tgagataatc cagaatgcta gtactactct agtggcaacc accatcacta gtatcatcaa 35460
gggcacttca tataaaagtg ccaatgtgca tcagggataa gaatgagaca tcatccactg 35520
gttcacagtg aactgatgaa acaagaacta cagttaggaa ttcattagga tcaacaggag 35580
tcctaaatat tagcaataaa ttaccacata acaagaaaca catgaacatg ggttaacaaa 35640
atgaaccact gacaagccaa cttttctgtg tcaaatttat tgtcctattg attttatttt 35700
aaagagatgg ggtatcgcac ggtcgtccag gctggagtgc agcgtcgtga tcatagctca 35760
ctctagcctc aaactcctgg gtcaagtgat cctctcaccc tcctgagaaa ctgaaactgc 35820
aggcacatac caccaaaccc acttaatatt tttttagaga cagggtcttg ctgtgttgcc 35880
cagactggtc tcaaaatcat gggctcaagc gatcctccta cctgagcctt cctagtagct 35940
gggattatag gtgcaagcta cagcactcag tgctcagact ctttggaggt gggaagggga 36000
acttatgaag tagaaagctt tgagaaacag acacctgctt gactttcacg gtgctattag 36060
aatagaaaat tatgcctaat atatgatgaa tcccttgcac gatcatcttg taaaagctac 36120
ttgttagaag taagcattca ccaagaccaa gtaaagaaat acatgaacca atacatagga 36180
ttaaataagg atttagaatt tagcttttta aaaaattatc tagcacatag tacacagcag 36240
ctggtcaata cacaaacaag aaactaaacc aagccgagcc cagtggctcg tgcctataat 36300
cccaccacta tggaaggcca aggtgggagg caaatttaaa aattagctgg gtgtgatggc 36360
gcatgcctat ggtcccagct actcaggagg ccaaggcagg aggaacactt gagcccagga 36420
tgttgatgct gcactaagct aggacagtga cagtcagaga tcttgttgca cagataaaaa 36480
aataaataaa aaaccataga tagccctaac aagatgaaga agaagaaaca tacgagcact 36540
attctcaaag tgtttaactt ggacaatgac agtcatggga aacaactgaa attcaatact 36600
tcaaattcaa aagcacttca atggaacaag tgacaagaag tttcttttcc aatgatttcc 36660
tctaaatatg gggaaattct attaaaaaaa atttttccca ggtaagatgt gagagatact 36720
ggcatgaaag ccaggcagta gaagctaaaa gtaaaaaaaa ggacaataaa acagaattca 36780
tttatgcttc tagcttacca tgtggacaca gaatatcttc attaaaattt aattcctcct 36840
cttcttttct ttcttccttt gattcatcta atcaaaagaa atacaaatga tatctgctgt 36900
ggttattgtg tacttaaagt tgaaagtagc agatatacta ctctgcacaa tttggaacaa 36960
agaaaacttt aaaactctga aaattagacc catgtgattc ctacacagtt ctgctaaaaa 37020
gtgttatatt tctttccctt aaaaggaaag aggaacatct caatgacagt taacttttaa 37080
agatttaggt tatgcaagaa aatgtgcttt tttaaattca aaaaatggaa ttcttctatt 37140
aattctagtc aaagtatcga gaatactgtg tcataaacca agttaatcat ctacatgtca 37200
tgtcatggca tgtcattttc acctacctac actttttggg ggtgaacaca aagcattaaa 37260
ggcaaattaa ataaggactt aacctttatc atcaaacaga gtactccccg ctgatcagtc 37320
agggcatatg ttctaagacc ctcaatggat gcctaaaacc taccaccgaa ctcaataaac 37380
atccattggc acatttctgt tcatgtcttc cacccacaag tttaatgcct tttccatctt 37440
aactcacact gtggccataa cttacagttt gtagtgtgac agcaaaacta gcatgaattt 37500
ttttccttct taatctcaca gacagatttg ttcctataga tcttagtaac ctcagcatat 37560
gatttttttt ctttccttat ttaaatcaag aacttacttc caccgttcca cttaaaggaa 37620
gcactttgtg gcttcttttt gacatacctg aattgccaac attaccactc ttccactttg 37680
agatcattat taagtaaaat aagggtaact tgaacacagg cactcctaca gtcaatctga 37740
gcaccaagag ggttgctagg tgaccagtca gtagcatgta tagcacagat aagctggaca 37800
cagggaaaac tcatgtcgca ggcaggatga agcaggaggg tatgagatac aatatcatca 37860
tgctactcag aacagtgtga aatttaaaac ttatgaattg tttacttctg gaagtttcca 37920
tgtaatattt tcagactgca gttcactgca ggttaactga aatcatgaaa agcaaaacct 37980
tgcataaggg tggaccacta tataataaaa actttgcttt tgctgttaac atttctcttc 38040
cagtatctgc ttttcttact tttttacact gtgtcactat caatttatag ttgtatatac 38100
tgggaacagg atcaaatgaa gaatccttaa gtatgattaa aatcattatc catgggggcc 38160
aggcgtggtg gctcacgcct gtaataccag cactttggga ggctgaggcg ggtggatcac 38220
gagatcagga gatcgagacc atcctggcta acacagtgaa acctcgtctc tactaaaaat 38280
acaaaaaatt agccaggcat ggtggcgggc ccctgtagtc ccagctactc aggaggctga 38340
ggcaggagaa tggcgggaac ccgggaggca gagcttatgg tgagcccaga tggcgccact 38400
gcacgacaga gcgagactcc gtctcaaaaa aaaaataatt atccatgggt tttccaggtt 38460
aagaacttca cacattttta ctacaattaa tacaaaaaat atctactaat cattcaaaaa 38520
ctgaagtaga ggccaggcac agtggctcac gcttgtaatc ccagcacttt gagaagacaa 38580
aggcaggcag atcacatgag cccaggagtt caagaccagc ctgagcaaca tggcgaaacc 38640
ccatctctac aaaaagtaca aaaattatct gggcgtggtg gcacgcacct ggggtcccag 38700
ctactcagga ggctgaggtg agaggactgt ttgagcccat gaggtggagg ctgcattgag 38760
ttgcaattgc gtcactgctc tccagccagg gtgaaagaga gagatcctgt ctaaaaaaac 38820
aaaacaaaac aaacaaaaac aaaacaaata aaaaaaaacc caaccaacca aacaaacaaa 38880
aaaaccccac aaaaatcaag taaaaaaatg ggcaaaggaa ggatacaacc agataattct 38940
gtctcctctt tttctctctg tcacacacac aaataacttc tcaagcctaa gaagatggtc 39000
aacctcaatg acattttgaa aaacattaag cctcaacact gctaagtcta acttcctata 39060
tcaggctgat aaaaactgat gtgactgccg ggcacggtgg ctcatgcctg taatcccagc 39120
actttggagg gctgaggtgg gcagattaag gtctggagtt caagatcagc ctggtcaaca 39180
tggcaaaaac ctctctctgc taaaaataca aaaattagcc cactgtgctg gtgcatgcct 39240
gtaatcccag ctactccgga ggctgagccc aggaggtgga ggttggagtg agccgagatc 39300
acaccactgc actccagact gggcaacaga gggagactcc gtctcaaaaa caaaacaaaa 39360
caaaacaaaa ctgatgtgac ggatgtattc tttatgttga caaaagcatg caaaaatgaa 39420
gcccctaata tgcatatatt gaagaaaatt taccaatatg tgtcagtatg tggcaattgt 39480
aagtatttat aattctctga tccagcaatt tctaggaact tatttctcag aaataatcgg 39540
aaaattctgt aatgatgtaa gtacaggaca caaaaggacc ctcactgcat ctgtgtgtac 39600
atagtcatgt aaaaaattaa aatagaatca gataaacata atggatccac aaaacaaaat 39660
gcaattaatc aataaaaagg gctgtatgtt ttgacaggga gagatgtaca actgtgccca 39720
tatgagctgt attataaaaa gccactattt acagtgattg tatctggtgg gaaggctttg 39780
aagttctact ttgtcacatt tgtgctgctt gaagcttttg aaatgtttta atgggggaag 39840
gagaatagag acatattact ctgaaagcaa catgaaaaat acttttaagc tatgccaaca 39900
tgaaggcact ttctattatg gcatccaatt ttactaaaaa tgaagggaca ctgatatata 39960
aagaggcctt tttctttttt ttttttgaga cggtgtcgtg ctctgtcgcc caggctggaa 40020
tgcagtggtg ccatctcagc tcactgcaac ctcctcctcc cggattcaaa tgatctcctg 40080
cctcagcctc ctgagtagct gggattacag gtgcatgcca ccacgcctgg ataatttttg 40140
tatttttagt agagaagggg tttcaccatg ttggtcaggc tgatctcgaa cttgtgacct 40200
tgtgatctgc ccacctcggc ctcccaaatt aaagaggttt taaaaagcag taaataaata 40260
tttaacacta agtcacatgt tatcattaaa attatagtac ggtttttcaa atgacaggat 40320
actagaactc aaattgatgt taagttcatg aattatatag cacaataaaa cattttaatc 40380
aaaagtaaaa actcagctgg gtgcagtagc tcacacctgt aatcctagca ctttgggagg 40440
ccaaggtggg cagatcactt gagctcagga gttcaagacc agctggccaa catggtgaaa 40500
ccccatctcc actaaaatac aaaaattagc cgggcatggt ggcacatgtg taatcccagc 40560
tacttgggag gctgaggcag gaaaatcact tgaactgggc ggagggacgg ggggcggggg 40620
ggcagaggtt gcagtgagcc aagatcatgc cactgcactc cagcctgggg gacagagtga 40680
tattccatct caaaaaagta aaaaaaaaaa aagtctcaaa aaagaaaata aaagtaaaaa 40740
ctcttcaagt ttgaaaatgt taatcacagc tcaaagagtt taaaactaat actgggttgg 40800
ttttcccaaa aagtaaggta gtgagatagg aagatcaata ccaaataaaa taaatataat 40860
ataaagtgac agaaatgggc gaggctcagt ggctcacacc tataatccca gcactttggg 40920
aagccaaggt gggaggatcg cttgagcaca ggagttggga gactagcctg ggcaacatag 40980
tgaggcctta tctctagaat ttaaaagaaa taaaaactgg tcaggcacgg tggctcacgc 41040
ctgtaatccc aacacttttg ggaggtcagg agttcaagac tagcctggcc aacatggtga 41100
aaccctgtct cttctaaaca tacaaaatta gctgggcgtg gtggtgtgca cctgtaatcc 41160
cagctactcg ggaggctgag gcaggagagc cgcttgaacc caggaggcag aggttgcagt 41220
gaggcggaga ttgcagggag ccgagactgc gtcactgcac tccagcctga gcaaaaagag 41280
caaaactcca tctcaaataa ataaataaat aaaataaaaa cttaaaaaat aaaaaataat 41340
gatacaaatg atatgaaatg cttgaatgca gaaaatacag aatatttcaa taaaggtcaa 41400
gaacattaaa gtaataaatt tccttgacat cttatgaacc actgattata gaattaaatt 41460
tagtgtttgc tttaaaacaa cataatttct gatttgaaag cataggaaac tcagaggaat 41520
ttacaaggaa aaagctattt aaaagctgcc ctctctattt gatgaaagat aaagaagtac 41580
aagctcattt acttgacaaa ggcagtgtgg cagataatcc aaaaccaaaa tgtactgagc 41640
atacaatata ttatgccaat ttgcagtaga cttaaccttt cttgaaactc ttagcctaga 41700
acagaattaa tattaatttt gcatgtgatt aactagagag agcttgagcc cgaagcatga 41760
taggttataa aggaaaattt cacatgtgag ttgctgagtc cttgctgaat ttcaatagct 41820
taaaaatctt ttatttgctc tgagctactt gtgagagctt gtagtttaat aaaagttgtc 41880
tttaaaatta catggatggg tatgaaacca attttgctca ttttttgggt ttttcttttt 41940
cttttttttt tttaagagac agagtctcgc tctgccgccc aagctgcagt gtagtggcgc 42000
aatcttgggt catggtaacc tacaactcct gggttcaatc gattctactg cctcagcctc 42060
ccgagtagct gggaccacag gtgtgcaaca ccactcctgg ctaattattt ttgtattttt 42120
agtagagacg gggtttcacc atgttgctca ggctggtctt gaacacctga cctcaagtga 42180
tcaacctgcc tcggcctcct aaagtgctgg gattataggc atgaaccacc gcacccagac 42240
taaaattgtt ttttagggaa acagggtctc actctgttac ccagactgga gtgcagtggg 42300
gctggcacaa ccgctgggct caagtgatct gcccgtctga gcctcccaag tagctgggac 42360
tacacgaatg agccaccgtg cctggcccac ttatattttc atggtatagt ttcacaatga 42420
tctacacata ggtttaaagt gttaccttta tttaaggtgc taccgttcat ctttccgttg 42480
ctttgttctg catcaccatc ttgctcatcc agctgttcaa gagctagctg gcgccaactc 42540
cgcaaggagg acttccccac ccaaaatcca tcgctgctgt ggaacagaga gaatgttaaa 42600
tcatataagt aatatttcca aacactgtcc tcccttcttt gcctgtaaaa acaactaaag 42660
tgaattacaa acactcaaca tcagctactg tacatgtaat tgattttaac ccacttccta 42720
atttcggtca ttttctctgt tcactattga actgcaggga tctaatattt tgtttccatt 42780
ctaaatatta tcctgctttt cctaccttca agccaatcac accaatcaaa tggtaggatg 42840
gaatacagtg gcaaaggcta tctgactcag cagttttctt tatcgttgcc acaggggcag 42900
tcattgcaaa atttactttt gatctggctc taccatccac tttatcaccc ttcttctaaa 42960
aatcccaact tcctattttt aataaataac gagatgcttg gttatgacct cttgaaaact 43020
tcttagttta tcattaacaa tgtacactgt gcaacatacc cctttactgc tgctttcagc 43080
agattattaa cagttttata atcttcattt agttggttct tcagacgcaa tatgcgacaa 43140
cgttctacta cacattcctt acacagggct ttcactacag gcaagaaaga atgaaaggaa 43200
atatatttca ttcaaacaga cttcctgtta ggaaaatgtt ttcagcactt cacaaacaca 43260
gacacattct aaaccaaagt cacaaatgtt ggcaatatgg caaattggta tataccctaa 43320
attattttac taagacaatt agaaaccaag acggcaatac tgttatctga ataaagaaca 43380
atgagagaca aaatgttgta ttacattaaa agtatctaaa tacagtatct gacaaggttt 43440
acatgcaatc tttacaagat gataatcaaa tcactgaggt tctaaggtgg gggggttaaa 43500
tatagctgat aattataaat aatgatcttc atgtgaaagt gatcttcaaa gcacactaaa 43560
aggaaaagca aaatgaaggg cctggtttaa aacacaaaga agttttagga atcatctaaa 43620
atgtgaacgc tcttcctatt gcatggttta ttcattgtga attaagaaca gtggcaggta 43680
tagtggctca taccaccaag agctttggga agccaagcag ggagggtagc ttgaggacag 43740
gagtttgaga ccagcctggg caacatagtg agaccctgtc tctacaaaaa gtgtaaaaat 43800
tagcaagcca tggtgatgtg tgcctgtagt cctagctact tgggaagctg aggtgggagg 43860
actgcttaag cctagaagtt ctaggctgta gtgcactacg attccaccac tgtactccag 43920
ctggggcaac agaataagac tctgtctcag agaaaaaaaa aaaaaaaaca ggggccagat 43980
atggtggccc attcttgtaa tcccagcact ttgggaggcc gaggcaggtc aatcacttga 44040
gcctaggagt tcaagaccag cctgggcaac atgatgaaac accatctcta cagaaaatac 44100
aaaacttaac caggcatggt ggtgcatgtc tgtggtccca gctacttgga agactgagac 44160
gggagcctga ggaggttgaa gctgcagtga gctgtgattg caccactgca ctccagcctg 44220
ggcaacagag tgagacactg tctcaaaaaa acaaaaacaa aaattcccag aaatttagga 44280
agcaaaactc cagtcgtgtt taacagaagg cctgcagcat gtagttaaat atcaagtttt 44340
atgcaataag ttgtatacca ttagaaaaca gcacttaatt acagaaaaag tgtattgggg 44400
agggaggtgt catgtaattt cctacagcct catctgaaaa ttggagggag gattgtgttg 44460
gcagctactc atgtaaaaag aaaaatgttt caaggaggca caacagaaag gcagccaaaa 44520
caaaatacta tggttgggta ctatgtggtc atatatagct ctatatttaa gggagaatca 44580
agtagcttcc attcataaac taagtaacca tctacagctc acacactgtt agaagtcacc 44640
atagctgggc gggtgtggtg gctcttgcct gtaatcccag cactttggga gggcgaggtt 44700
gagtggatca cttgagccca ggagtttgag accagcctgg gcaacacagt gaaaccccgt 44760
ctctactaaa aatacaaaaa ttagctgggc atggtggtgc gcacctgtaa tctcagctac 44820
tcgggaggct cgagaatcac ttgaacccag gaggcgaagg ttgcagtgag tcgagattga 44880
gccactgcac gccagcctgg gtaacagagt gagactccat ctcaaaaaaa aaaaaaaaga 44940
agtcaccata acatggaggc acaaacttgc aattaaccag acaagggctc aagtacctta 45000
aacagtatta cacagagtaa caaactacta ccagacagtt ttcttaaaag ggtcctattt 45060
tgtctgcttt gagaggggtt aaaagaaaca aaccaaaaaa acaaaccaaa aaaccccaac 45120
caaccctcta tgaatagcat cagttgctta acttctactt tatttagcaa atcctttgtg 45180
caaagtgtaa ggaatatttg gtctagcata gtttgggtca aatcatcata agccacactc 45240
ataaagacca taagatgaag atttaatgag ctgctctttt ttaaacagag aggacatctt 45300
gaattaccag ttagtcttgg acctcctcca tatctactat agaaaatgtc agctgcatat 45360
tcagatatcc tcttcataat tgatatttta tccgggtgaa gcttgtcatg ggaacacagg 45420
caagcgtgat tatcaatagg tttggtaggt gttgattcat ccaaccactt ttgcagccat 45480
tccagagaga caaactcata gggctctgag aaagcaagca tcggaaagag cctatgtatt 45540
tttacagttt tttgactaag tgatacattc atttttctca aaagacaatg caaactctgt 45600
ccagagttag cagaatcaga agaatcattg tctgggggaa gatgtttgat gagtacgaca 45660
caaagctcca gttaagtgcc actcctatga gttcaaggag ctgtgcacca taatgctgag 45720
tctgcacagt gccctatgag atcggctggt attattaacc acattctaca agaggcatcc 45780
acatagagtc ttgccgaata gcacagcaga gctttgatca ggacacccat gtttgttgac 45840
tacaagtcat gctccattgc tgcctcacaa ataacacaac ctcatgccct actgtgttta 45900
tttcataaat tatttttgtc agtacttttc acatatatgt gatatacatc tgaaaattaa 45960
aatgagaagc caaactgaaa taaacctcac cgactatgac cacacttcag aagacgcttt 46020
taaccactga actttcttca tccaagatga tactgatggc aattttgaaa aggtatttaa 46080
ttcccccacc caaatccaag tcatgatctc ttcattatat tattatttat ttcaagaaag 46140
taacctattt taaacaagtt cgaggataaa gtacactaga actgagtcat caattttgaa 46200
gttgcaaaaa ttaaaagaca aaaccaaaca cctcaaaatg agttttaatt tggggaaagg 46260
aagtccctag aattccctaa aagccaaaat caaagataaa gggccagctt tgattactta 46320
caaagatctc cagtgagtcc cagcataaaa catagaagaa aacatacaga ggttgaattt 46380
atatttttgt attatatact ccttctgatg agatctgagg gacagatact tcaacgcaaa 46440
gcccattgtg accagtttta tactccccag agagttacat gtctagaaaa ctaactccca 46500
ttttaatttt acagtaaacc atctcaattt ttatgaaaac aaaatttggc actgtacatc 46560
atcaactaag agccttctaa ctggtcaagt cgaatgtggc tccagaggaa gagcacagga 46620
ctgtgagtcg aggtcacggt ctaatccaag ttctgctacc aagaaaatga acctgaacaa 46680
gtcacttaaa ctttctatgt ttccagtctt ttatttgtaa aatgaaggta ataatacctg 46740
ccttctacct acctcatggg aatgttgttg agtataaaag ataagctatg tgaagcattt 46800
tgagcttttt ggaagaaaag agatatggaa aagttaatta tacatttacg taaacttaat 46860
atataaaaga ggagaccttg gctgggcatg gtggctcacg cctgtaatcc tagcactttg 46920
ggaggccgag gcgggcagat cacctgaggt ccagagtttg agaccagcct gaccaacagg 46980
gagaaacccc gtctgtacta aaaatacaaa aaattagctg ggcatggcgg cacacgactg 47040
taataccagc tattcgggag gctgaggcag gagaatcact tgaacccggg acgcggaggt 47100
tgtggtgagc tgacattgca ccagtgcgct ctagcctggg caacaagagt gaaattccat 47160
ctcaaaaaaa aaaaagagga gactttaaga tgcagtatat gtaacacagc tgcagcactt 47220
tacagtatat catggtatgg ctaattacat tcaaaatgcc tcccgacttt atttgccatt 47280
tatcaagctt aatctgccag ggatagagta cactgggtat ctggggaatg caaagataaa 47340
tgatcccttt ctgaaagcaa gatcaaagtc ttagcatact ctcatctttt cccaaggaca 47400
gtcaattaga ttaaaatggt aagcaatatg aaggctatca aaggagaaaa aacaggattg 47460
tgataaagag caacattcaa gaataagtca ctaggcatcc tagtttcccc agcagctggg 47520
gaggagtgga cagacagcag tatctgttat tgctaactga aagaaaacac cctaagaatc 47580
ctggccctca caatgaaagg aatctaggaa agctcaaaat gcacaaagcc ctccttgcca 47640
ggggatgtct gcaggaattc aaagcctagg gtgactgtgg ccctgactgt ccagcaacaa 47700
tgtggctcaa aggcaagaca acattttcca atctcacaga aaacttccaa ggaaagcttg 47760
ttgttttggt ttttgaattg ttcaatataa atttaatgta agatacaatg attagaaaaa 47820
ctatgtacgg ttttatagta agaggaggaa gacagaaagc agagaacagg cctataattc 47880
taatctaata ccatgcttac tactaacagc aagttctcca gatttcactt tagtgcgctg 47940
tgggctccat gaaggaagag tgactatggt cacagaagtc tgtctttctt tccattttca 48000
gtctctatca tcataaagag ttgcactgac tctgccaaga gcttgcctga gaatacaagt 48060
ggagcacaag tctcatagtt aaggcagatt ctgtttgtgg caaagttttt acactacaga 48120
tgtttctgca ctagaaaaag actctaagta ggcccctcaa atatattccc tagtatttgt 48180
gattcagtaa actacaagca ttgctttcca aaggccatgg acataatcaa ctccaaatga 48240
gggagaactc tcctattatc aagctggaga taccggacta tatgaaacct cagcatttga 48300
tgaggaaagc aaaatattaa aatatttacc acagggaaat atacattttg gttcaaagtt 48360
ctttaaaaag aaaaaaaaaa acctggattt tgaacatgac acattttctt tggaaagtta 48420
taaagtctag aacaatcaca gcatcaaaaa catctgaaac actttaccta gagataattt 48480
aagtatattt caatggaaat aaaaagggcc aaaagcacgt tcctactgag gcttagattt 48540
tagggtaagt gatctttgtt tttttaaata tgttcacaca caaaaataag atttagaaaa 48600
tgcataacaa aagacttctc ttgccagcac aaaaccatgc tcattaactt tgagattcta 48660
cataatttta cagcgtggac tgtctacaat ataagtttac tgcaaatgga aaagaattat 48720
atagctcata attggtaaaa gtataaataa cacagagaaa tactctaaga acataagcat 48780
attctaagaa cataaggttc ctatatgctg aatgaaaaca gccaaaggaa gcacagtgct 48840
aacttgacac ataacatctt tgaactctat agttctaaag agtggttcaa atgagtattt 48900
cactttagac ccagttaagt ccctttctct tgcccagtgg acacaggaaa ccgtgaataa 48960
agtttggaaa atagatttct aggtcccaac acctttgaac aaagacctat aaatttagag 49020
atctgaatca tgggttcatt tccaaatcat ttccagttac attaaggtca gtttaattat 49080
ttagggtaat cccaaccctt ggacagagtt aaagtaacag attacaaaga agggtcagaa 49140
ttgaattaaa atttagttaa aatatattct tatagacttg gcaatttttg tttacatttt 49200
gcttaaagtt atactagtaa tggaaaatta agatattaaa aagacaaacc acaagtacaa 49260
ttatgcttaa gtatttattt tctaaagtaa ggactaaatt gtctctcttc cttaagtagg 49320
aattaggctt ggggaattca tgtctttaaa atgacaaaga taacttaata caaatggcac 49380
atcagccttt aaaaaggctt aatttggttt cattttgaga catcaggtaa acctgaataa 49440
acatatacag aaaagggata agctggatta tgtgggatat ttctaagaaa tcaggggtca 49500
gcagaaagct tttctactct tagcataata tttggtatta aacttcaagt taatctaata 49560
gtatcaaaaa aactgtattc atataataga atgtctgtta aaactgttag gtcacaaagt 49620
atgcaaagaa acagaacagg caagttgctt tttccatagt aatccaatcg gatttttctt 49680
aaacaagtta atatctcaca aaatataaat atctacaata ctcatggatg cagagtgctg 49740
acctaaatgt tataatttat taacagcttc ccatttttag gagtacaacg taatgaaata 49800
atatggaatg ctacacatca agttattgtt ggtttacaaa gtacttttag agtgtttaag 49860
ctggctttag tgggttatta gaaagagtaa gtttgagaaa gtttcttcat atacatttgt 49920
gaacataaaa aaacaaggca cttaatggca acagtgctgt cccagaatat cttacagacc 49980
agctccagca ggtaaccttt ggtacagctc cttaacctct tcgtgttttg cttttccttt 50040
atccacactt tgcttacgca tctcagccat ttcaatacac cactcctcaa atttggaatt 50100
atcccgatct accagctctt gaagaaaggc tattcaaaac agaaagacaa aaaacaactt 50160
tattcttgtt ttcacatata gtgaaccatg ctaatctcta aatcatatca aatactgatt 50220
aaaacattgg cagaaattcc aactatggtc tccctgtctg ctagaaacct ccaaactgaa 50280
ggcagaagta aaagtgaaga cagccactgg aataatccta aattgattcc ccccacctag 50340
ctctccatga catcatcagc ctcccagaac aatcgaatgg ctcaaaatca ccactttaga 50400
atagatgacg ccaggcgggc gcagtggctc atacctgtaa tcccagcact ttggaaggct 50460
gaggcgggtg gatcgtgagg tcaagaattc aagaccagcc tggccaagat ggtgaaaccc 50520
catctctact aaaaatacaa aaattagctg ggcgtggtgg cacgcacctg taatcccagc 50580
tactcgggag gctgaggcac agaactgctt aaacccagga ggcagaggtt gcagtgagct 50640
gagactgcac cactgcactc cagcctgggc gaaagaatga gactccgcct caaaaaaaaa 50700
aaaaaaagaa agaatagatg atgccaccaa gcttagaaaa gtgctgagta aaatgattca 50760
gactcagact gtcttcaggg cagcaacaac tctacctttt atattatgaa gtctagaata 50820
tctatagata attaaataaa attcacaaat actctataaa ccgaacaaaa taaaaccaaa 50880
ttatacttta aatacatgtt ttgattactt tctgattttt taataattgc attgctttat 50940
ttcagaagct cctttcttaa aagtaaattt gcaattaata tttactttca ccaacattca 51000
ccttatggaa tcaatttatc atagtaacta aaagcaatcc attacttatc attaatcttt 51060
gagtatggca ttctaaaaca tttgcctgct ataatcctgg aaaactgctt tacctggaac 51120
ttgaacagta gtgttgggct tttcttgagt ttgcagtcta taaaccaaca tatatgcatt 51180
tcgagagcaa tgagttcctt tgccacactt gggtttacgt gtctgagact tagaaggttc 51240
tgctgagata gagaaatcaa aaggtacctt aacttaagtg cctagagttt gtttattctt 51300
tagcggggct atagaaaaca atttccaaaa tatacaccca agacacatta acaccaatct 51360
aaaacattca aaggccatag aaatttggca ggctctttag ctttaatatt taaaaaagtt 51420
tactaccact attgcctgcc acattctatt ttttaaaggt aaaaagaaaa tacatttttc 51480
tggggaacaa acctagaaca acaacaaaaa aatcactatt gccataagct gatttttatg 51540
ttagtcttaa attacaaaaa ttaactgaag ccgggcacag tggctcatgc ttgtaatcat 51600
agcactctag gaggccaaga tgggcagatc acttgaagcc agaagttcaa gaccagcctg 51660
gccaaaacat ggagaagccc tgtctctact aataatacaa aaattaagca ggtgtggtgg 51720
tgcgcacctg cagtccacct acttgggagg ctgacacaag tgaatcgatt gaacccagga 51780
ggcagaggtt gcagtgagcc gagatcacac tccagcctgg gtgacagagc aagactctgt 51840
ctcatgaaaa agaaaaagtt aaattaaatt aaattaaaaa ataaaaacag gccaggtgcg 51900
gtggctcaca cctggccaac atggtgaaaa cccatctgtc taaaaacaca aaaattagtc 51960
gggcatgttg gcacatgcct gtaatcccag ctattcggga gcctgaggca ggagaatcgc 52020
ttgaacccag gaggcagagg ttgcagtgtg tcactgcact cctgtctggg ggacagagtg 52080
aaactctgcc tcaaaaaaat aaataaataa aaatcaagac tgatgcaatc actaaaggga 52140
atatgggact tcaactctac tggaaatatt tttattcttt tttttttttt tgagacagtc 52200
ttgctctgtc ggcaggctag agtgcagtgg cgcgatcttg gctcactgca acctctacct 52260
cctgggttca agcgattctc atgcctcagc ctctcaagta gctgggatta caggcacgtg 52320
tcaccacacc cagctaattt ttgtattttt agtagagaga agatttcacc atgttggcca 52380
ggatggtctc gatctactga cctcacaatc tgcccgcctc agcctcccaa agtgttggga 52440
ttacaggcgt gagccactgc acctggctga aatattttta ttctcaatga ttgcttggta 52500
cacaagtatt tgttttaatg ttgtttttta ataaaagtat atataaaatg tatatgtaca 52560
gtttgaaaaa taaaaattag ctcagtaatc attttagtaa acagattttc ttcaatttag 52620
tcaaaataat acaaataaat ctagacttaa ttgcccaaat aaataaaata gcatattttc 52680
ttttcttttt ttgagacaga atttcgctcg tctcccaggc tggagtggaa tggcacgatc 52740
tcagtgtact gcaatctctg cctcccaggt tcaagtgatt ctcctgcctt agcctcccca 52800
ttagctagga ttacaggcgt gtgtcaccac gccagggtaa tttttgcatt tttagtggag 52860
atgaggattt accacgttgg ccaggctggt ctcaaactcc tgacctcagg tgatcctccc 52920
tcctcggcct cccaaagtgc tgggattaca ggagtgagcc accccaccca gcctaaaata 52980
gcataatttt taaaaatgaa atgaaatggg ccaggtgcgg tggctcatgc ctgtaatccc 53040
agcactttgg gaggccgagg caggtagatc acctgaggtc aggagttcga ggccagcctg 53100
gccaacacag taaaagcccg tatctactaa aactataaaa attagccagg ggtctgtaat 53160
cccagctact caggaggctg atgcagcaga atcagttgaa cccaggaggc agaggttgca 53220
gtgagccaag atcacgccac tgtactgcag cctgggtgac agtgagactc agtctccaaa 53280
aagaaaaaac aaaaggaatg aaatgctaac aaccagaaac attagccact aatctctatg 53340
acgtaaacag caactggaaa acatgaagtg tttcagatgg caactatagc acatgaaaac 53400
gattttcaaa ttgggtttca gcgttccagg taactttccg agaggtaagg gattatagcg 53460
gcggatcatt tgagatcagg aattcgaaac cagtctggcc aacgtggtga aaccccatct 53520
ctactaaaaa tacaaataat tagccaggca tggtgacgcg cccctctaat cctagctact 53580
tgggaggctg aggaaggaga actgcttgaa cccagaaggc ggagattgtg gtgggccaag 53640
atagcaccac tgcactccag cctgggcgac acagtgagac tctgtctcaa aaacaaaaaa 53700
agaggttatg ggcagttcta aggaaatcca gttaccagat cctcaattca ccacgtgctt 53760
ttctaaaatg gatctgcctc aacactgagg tcccacgatg gtttctacct ctcttttcac 53820
aatcagttga ctcccacgtc acaaaagaaa gatataacct ctcagccagt gacagaaaaa 53880
ggtctcatct atcacattga gatatattta caaaaaaagt acatttacag taaaatttta 53940
ctgtttaata aaatttataa catactttca tgagttttat caattatgta gtaatattca 54000
taattttaaa aacagcactc tatccagaag tactttttaa ctatttagag ctttacagtc 54060
acaaaaaact tactatattc cattagaata aaattctgta gggtaaacat aatggaaata 54120
gtagtacaga agaaaataga attgttaaaa atgcctacta taaaacaaga cctgttcagt 54180
tatccttgaa aaggatgctg gtggatataa aacctctatg gtatttaata taatctggac 54240
attcttaaaa gagtgatgtc acaatttaag tttcagtatt cattatgtca taaattatag 54300
catttggagc tacttaaaat ttatgatgaa atttgttaga ttttaaaatg tgcaaagaaa 54360
aaaaaagttg ttcaactttt tttgttttcc cttgcaccta tgcttggatg ttaaacattc 54420
ttacagacaa cgcctgaaca aaaaaggttg gaagatcact gtactgtcac agggaattaa 54480
aataccagga acatgcacag gtaagaggag gttagtcatc cattcctaat taagagtacc 54540
caaggctggg catggtggct cacgcctgta atcctagcac tttgggaggc cgaggcaggc 54600
ggatcacttg aggtcaggag tttgaaacca gcctggccaa catggtgaaa ccccgtctct 54660
actaaaaata caaaaaattg gtcaggcgtg gtggcacgtg cctgtaatcc tagttactca 54720
ggaggctgaa gcaggagaat cgtttgaacc tgggaggtgg aagttgtagt gagccgagat 54780
cgcgccattg cactccagcc tggccgacag aggaagactc tgtctcaaaa caaaaaaaag 54840
agtacccaag atttaagatg ttaatgattt tgtataagat ggaatataaa atgattcata 54900
aaacttcagg atacaacata ataatgaatg tctaatgaaa tttaaaaata ttttctattt 54960
ttgatttaaa agatgaaagc taaaatatat gctgcataaa atagtgagtt atgaaaacac 55020
tggaatgaga taccaatggg tgttaagtat tttcttgaac tgttttaaaa tctaggacta 55080
cccatatata agacagcctt aacaatgctt ttaatcctag aatgtagata gattttaaaa 55140
aaacccagta aaaaacagtc aaataaaacc aagacataat ttttcacaat ttaaagttct 55200
tttttttttt cttttttttc agacaaggtc tcactccgta gcccaggctg gagtgcagtg 55260
gtgcaatcat ggctcactga agccttgatc tcctgggctc aagcatcctc ctacctcagc 55320
ctcctaaagt gttgggatta tagatgtaag ccacctcgct caacccagtt aatgtgctat 55380
ctcaattttg ttcctagtaa gaatgtcata atgaaaacat acactgtata agcaaatgtt 55440
gagaatttga gttttactta ggtaaaatgg gagcgagatt gctgaagttc tataaacaca 55500
gaaatgttat ttaaaagtag aaaacaggtt gggcacggaa gctcatgtct gtaatgccaa 55560
cacttttggg aggccaagtg caaggatcgt ctaagggcag gaattcaaaa gcaacctggg 55620
gaacccaggg agactctgtc tctgtaacaa attacaaaat tagccaggtg tggtggatca 55680
cacctgtggt ctcagttact tgggaagctg aggcaggagg attatttgag tccaggagtt 55740
cgaggctgca gtgagccatg ttcatgccac tgtactccag cctgggcaac agagcaagac 55800
tctgtctcaa aaaaatatat aaataaaagg aaagaaaata aaatttaaaa gtgaaagaat 55860
gacttctcca agctacatga atggagttaa caaacgatta tctgtagaga tgatgcatat 55920
gcctcgaaag caaatctcaa ctgctatgtt cctgcctact ggacaccttg aataaatgtc 55980
tctgacctat taagaaagaa gagtggcagg agacacacac ttactcccat ttcttttctc 56040
caattcagat accatagtct gaacctcatc caaagctgtt tagcactttc ttgtgaaatg 56100
atatgaccac acttgtgagt ctgcatgtgt catctcactg tgctgtgtgt tagatttcca 56160
gaacaaagta tgtgcccttg gacaattgcc tatacctgtc tgacagacaa tgggaagaaa 56220
gtgataaaca gctcaggaga tggagctcag gagatggctc caactagaaa aactgtccat 56280
tcctttggaa aataaatggg tacttaggcc caagacaact gaggtgatga aagtacatac 56340
taggatacta ttttaagaag tagtctttat ggcagacctc actactacac agtagcaacc 56400
agctcatttt ccacagaagc actgctcaag gatttgggta agatacttaa aggaaggaga 56460
aacaaagttt acctgctaga attagttccc caaaataaat ttcctgaccc aaggaaaata 56520
attacaaatc ctactacatt aaatctacta ttcatcatca ctaacttaat gcccatgatc 56580
ctcccctacc cacttaaata aacctggtaa ttaaaaactg atcatttgcc ttcaagcttt 56640
actgaaaaca tgacattatg aaaaccatct ctggaacaaa ataattgtaa atttttttaa 56700
ctaaaatttt aaaaagcaag cattgctacc tgggcgtggt agctcatgcc ttgtaatccc 56760
aacactttgg gaggccaagg cgggaggact gttaaactca ggagttcgaa actagcctgg 56820
gcaaccaggt aagaccccgt ctccacaaaa aaattgtttt aaacattttt gccaggttgg 56880
ccgggcatga tggttcacac ctgtaatccc agcactttgg gagttcaagg caggcagatc 56940
actggaggcc aggaactcaa gaccagcctg gccaacacag tgaaaccctg tctctattaa 57000
aaatagaaaa aattaaggcc aggtgcagtg gcttacgcct gtaatcccag caccttgggg 57060
ggccaaggca ggtggatcac ctgaggtcag gagttcgaga ccagtctgac caacattgtg 57120
aaaccttgtc tctactaaaa atacaaaatc agccagccgt ggtgacacat gcctgtaatc 57180
ccagctactt gggaggctga ggcaggagaa tcacttgaac ttgaaaggta gagtttacag 57240
tgagccgaaa tctcgccatt gcactccagc ctggacaaga aggcaacaag agcggaaaaa 57300
aaaaaaaaaa aaggaaagag aaggaaaagg aagaattagc tgagcattgt ggcacatgcc 57360
tgtaatccca gctactcagg aggctgaggc acgagaactg cttgaaccca ggaggcagag 57420
gttgcagtga gccaagatgg tgttactgca ctccagcctt agtgacagag taagactctc 57480
tcttactgaa aaaaattttg acaaaatttt tacctgacaa aaaaaatttt gtcaggtgtg 57540
gtggcactta tctgtaggcc cagctactag gaagggaagg ctgaggcagg aagatcactt 57600
gagcctagca ggtttaggct gcagtcagcc atgactgtac cactgcattc cagcctgggc 57660
aagagagtaa gaaccggact cgaaaaacaa gcattgctaa tacaagatgt tcagtgattt 57720
tacatgtgtt taagaaatgc aaatatcctt gatagtctgt aacataacaa tcttgagcca 57780
taataattta tcacaaatat ttctagtaaa ataaatttat attttaaaag ggcactcaca 57840
acttaaaggt tttacctaga tcttcctcaa tccctagttg taatttcttc ccctccatct 57900
tttctatgtc ttcatcatta aacttatacc attcaccaga ctgtggatct ttcacgtggg 57960
cgatgtagtg gccagaataa gcactcactc ctctgtgtat gaggactgcg ctgagttcat 58020
acacgtagga cccacctgga gagaaaggga gaaagtaaaa gaaacgttgg ataacagtta 58080
tttcttatat cctgagcctg aattgtaatg attacgaatc tttacacatg tggtataact 58140
aaaaacatgt cacctaaaat ttttacaaat tagttttaca aaataatgta taattacact 58200
cccttaacac tctcttagac acactctgaa cagcacactg tattaattct ccaagcctct 58260
gcaaaataca cggatgaaaa actacggcct cctgggcact cagggaatat aagctactct 58320
actacacacc gtgctcttca gcacacacta gcgaggccac acgcttccca agaatcggct 58380
gttcatactc tctgtgtgtt acgaaactta aaacttatac aaaccaggga gacacgaatg 58440
tcaaatgaaa aggctattgt ttatagaaga gaagataaat gctttggcaa aaactgacgg 58500
caagtcatga aaatttgctc tcaaaacagg tgtaggcatt tgtccaaggg cacaaacttt 58560
gatctggaga tctaacaccc agcgcgttga gatgacacat gcagactcac aattgtggtc 58620
accatttcac agacacatgt atcatcacat tagcaccttc agatcaaagt ttcatttgcc 58680
aagtctacct cattaaagct ggaaaaaaat aaaaataaaa acaggtgtag gccaaacagt 58740
tggaaaatat agggatgaaa acttaaaaaa tctagaatga tactgcactc agatttcttc 58800
gtattttaag ttcctatgct attttaatta aataaaatct acaaatcata gcctatattt 58860
tacacggtat tcaaaaagaa aaggctttat acatacatca aaatattgac aataaatgaa 58920
catttacatt tcaaagtgaa ctaaaatgtc ttaaaatttg agaaacatct tgtaaagatc 58980
ctcaacttaa agcaattatg gggaaaatgt gttagaaaag atcacttcca ctatacatgt 59040
tctgttattt actggaaaac aaaacaattc attaataaac ccacataacc acaattaata 59100
ctgaaaccta cagttttttt ccaacaaata atatcttttc acatcattat tcttctaaaa 59160
attacttata atgactatat ataattacca taatatgcct aaccacatcc acattaatga 59220
acacttattt aaactggtaa tgtttgaggg cctttataag caataataat tatctttaca 59280
gtacaaatct ttgcacagat ctttgacaat tttttttttt ttccctgaga cggggtcttg 59340
ttctgtcacc agactagggt gcagtggcac aatcatagct cactgcagct tcaacctcct 59400
gggcttaaac aatcctccca cctcaacctc caggagtagc tgggatgaca ggtgtacatt 59460
tttatttatt tatttattta ttttgagatg gagttttgct catgttgccc aggctggagt 59520
gcaatggcgt gatctcggct cactgcaacc tctgcttcct gggttcaagt gattctcctg 59580
ccccagcctc ccaagcagct ggggttacag gcacacacca ccacacccgg ctaatttttg 59640
tatttttagt agagacgggg tttcaccatg ttggccaggc tagtctcgaa ctcctgacct 59700
caggtgatcc atctgcctcg gcctcccaaa gtgctgggat tacaggcata agccaccacg 59760
cctggccttt tttttttttt ttgagatgga gtttcactct tgttgcccag gccagagtgc 59820
aatggtgtga tctcggccca ctgcaacctc cgcccccctg gggtcatgcg attctcttgc 59880
ctcaacctcc caagtagctg agattacagg cacccaacat catgcctggc taagtttttg 59940
tatttttagt agagatgggg tttcaccacg ttggccaagc tggtctcaaa ctgcaggcct 60000
caagtggtcc atctgcctcg gcctcccaaa gtgctgggat tacaggtgtg agccaccacg 60060
cccggcccat tttttttttt tatagacagg gtctcattgt cttgcccagg ctagaatttg 60120
actatttcat tgctataatt tccttaaaaa tgcaaaagag tacatcacag cagagtatag 60180
ccaatcactc attagacaaa cagtaaacat actggacacg gtttcaggca tgaaggatac 60240
agcagttaat taactaaagg aacagagtcc ctgcattctt gaagcataga tggggaaaca 60300
gtaatgcaga ttaatacctg ggccaaaacc cactgaactc accccagctg aaaacactga 60360
agatactggg taagataaaa atatttttaa atctttctaa atgcattgtc aagaaaataa 60420
gaattatcag aagcccaata ccatgtgaag gcaataagcc atgtagtaag gacaacagag 60480
tttccctctg cgagtgttag gggaacacta tgatcgactt gaactctgtt tttccgtatc 60540
tcaaagggct tacgggatca gagacaacag ctaaggttca taaaaggtga ggagtctaac 60600
aggggactcc caccaggaaa ctaaggtttt tttttaattg acaaacaggc tgggcgcagt 60660
ggctcacacc taaatcccag cactttgtga ggctgaggca ggcagatcac ctgaggtcag 60720
gagtttgaga ctagcctggc cagcatggtg aaaccccctc tctactaaaa atacaaaaat 60780
tagtcaagca tggtattgag tgcctgtaat cccagctact caggaagctg aggcaggaaa 60840
actgcttgaa cccgggaggc ggaggttgca gtgagccgag atcatgccat tgcactccgg 60900
cctggaaaac aaggcaagac tccgtctcaa aaaaaaaaaa aaaaaaaaaa aaaaagacaa 60960
ataatatttg catatattta tgggtacaat atgatgtttg atatgtttac atcatggaat 61020
gattaaatca agctaatata tccattttct gtggtgagaa cacttaaaat ctgttatttt 61080
agctatttca aaatgcacaa cgcattatta actgcagtca ccatgctatg caataaagct 61140
ccaaaactta ctcgtcctgt tgaaccgaag ctttgtactc tttgaacatc acctccccat 61200
tcctcatcgc ctctgccatc caccacctcc actccctggg ttctggtaac caccattttc 61260
ttctctgttt gtacgtgttt gactttttta gattctatat atagtatcga tgagatcatg 61320
cagtatttgt cttttttttg agatggagtt tggtcttgtt gcccaggctg gagcgcaatg 61380
gcgctgtctg ggctcactgc aacctccacc tcccaggttc aagtgattcc cttgcctcag 61440
cttcccgagt agctgggatt actggcatgc gccaccatgc ctggctaatt ttgtattttt 61500
agtagagacg gcgtttctcc atgttggtca ggctggtctt gaactcccaa actcgggtga 61560
tccacccgcc ttggcctccc aaagtgctgg gattacaggc atgagccact gcgcccaggc 61620
cagtatttgt ctttctgagc ccggcttgtt tcacatagca caatgtcctc cagattcatc 61680
catgtgatca cacatgatag agtatccttt ccatttaagc ctgaatagta ttccattgtg 61740
tatatatacc acattttctt tgaaactaga attctttggt ttagaagatt atcaaaatga 61800
atctgctctc cacaggaaat ggtaagagaa aattatctgc cttatactta tattttggga 61860
cctaggggta aaaatcaaaa accaaaagga aatctccatt acaacttcat aagaagctag 61920
ccctcaaaaa gatttcttta ctatgatttc acactaccta tgaagtcaga aaaaccccaa 61980
gccaagagtt ttgtttgatg tggtcctggg acgagtgaca atcctaagga atgagtacca 62040
tcaaaacaca cacatgtcac atcacaagtc actctaactg caaggcagca aacagcaaca 62100
aaatcaaact ggtgaagatt ttcacctcag tcagtggaaa tagcaaatac ataaataaaa 62160
ttttaagtat gtttaaagaa ataaatgatg aaattaagag gaatagagat tacagaaaat 62220
gaaaatcaaa tgacgaagaa ccaaatcaaa ctccgagaaa tggaaatcac agtcaccgac 62280
agtcaaaact ctataaatgg tttaacctca gatcaggttg acctgaacag agaacgaata 62340
aagtacaagg tagagctgaa gaaattatgc agaatgcagg acaaatgaat gaagagttgg 62400
gcgacatgca acatagagta agaaaatcta acacatatct aactggcatt ccagaaggaa 62460
agggagaaga gaaaaagcat tcagaggtaa tagttggaaa attttcagat gccctaggtg 62520
agaataataa atcaattaaa aatcaaacca agtgttacag ctcttttaga atttgtctag 62580
caggttttcc tactagaaaa ccagaaaaga tttttaaaga atcaaaatta aaaaagaaac 62640
caaaccaaaa ttggtcacag tgacactgca agataccaaa accaaagaag aggtcttaaa 62700
attagacaaa acaaaacagg cctcttgtag agacaagaat tagactgcaa ccaacttttc 62760
aacagcaaca acggatgccc caaggcaaca gaatgctatc ttcttcaatg atatcttcaa 62820
tgagtgaaag taaccaccca tgcttagaga aaatgaattt cgcaaggaca aaatagacac 62880
tttcagacaa taatatgtga aaagaatctt tcacccacag acccttacta aaagaatttt 62940
gtaagctcta attcaatagt ttaaaactct tccagatgga aggtctagaa tgcaaagaat 63000
gataaacaaa ggaggtgggt aaactaaaca ccaagattcc tatataagat agtctgtaag 63060
tttctttttt aaaaaaggta gaactaaaat acatatgaaa aataggccag gtgtggtggt 63120
tcacgcctgt aatcccagga ctttgtgagc cgaggcaaga ggactgctta aggccgtaag 63180
tccgaaacca gcctgggcaa cacagagaga cccagtctat aaaaacttaa aaaattaacc 63240
agacatggta ctatacacct gtggtcccag ctactcagga ggctgaggtg ggaggattgc 63300
ttgagtctgg gaggtcaagg ctgcagtgag ccatgatcgt gctacactgc actccagcct 63360
cggtgacaga gcaagaccat cttaaaataa tttaggagag tgtcgattgc ttaatgtttt 63420
gagatcattg agggtaaaga tgttatctag agagttaaga atacatgtta taatttctag 63480
ttaattatta gtattagctg gcccaggcta ccctaggggg cattttcata ctccaatttt 63540
agggtttact tggaatcacc ctccactgtt ctttctactg cactgcactc tccccgttac 63600
ttcatgttaa aggtgagcca gaaaaagcct atcttcctaa cctcagggaa ccataaagag 63660
aactcctggc tgggcacagt ggctcattca tgcctgtaat cccagcactt ttggaggctg 63720
agacaggtgg atcacctgag gtcaggagtt cgagaccagc ctggccaaca tggtgaaacc 63780
ttgtctctac taaaaatacc aaaattagcc aaccgtggtg gtgcacactt gtaatcccag 63840
ctacccgaga ggctgaggca tgagaatcgc ttgaacctgg gaggcggagg ttgcggtgag 63900
ccaagatcgc ggcactgcac tccagcctgg gtgacagagc gagactctat ctcaaaaaaa 63960
aaaagaaaag aaaagaaaaa gaaaaagaaa aagaaaagaa aagaaaagaa aaaaagaaaa 64020
agaaaactcc tgagtcctga acagagcggt agaaataaaa aggagggaga tgtgatggtc 64080
ttagattgcc cataccaggt tcttccagtc tgtgtaagcc agggaacctc aagccttgaa 64140
ctctgtaatc atacctaacc agcagaggcc ccaaatgcct gacagaaata aacctaaagg 64200
gctttgtgga ggagatggca tgtatcctag ccctagggga atccccataa ataattctct 64260
atgtgcaata accagcatgc agtcaaagac aaccatgaac agaagcaaca aaacaacact 64320
gctataacca gctcgggtag agagatcagc ctgaacaata ttccaacatg gtcagtaatg 64380
gattataaaa actgggtgtt tttaacgttt aaagtggttt aaaaattttt ttttaatatt 64440
ctggatacct ttaatacatt tatgaacaaa tactgatgac aactcatttt aaatatatca 64500
ataactgaga aaggtgatat atttcttttt gtggctctat tgaccctaat tggtcaaaag 64560
cacctcattt tgcaggctgt gggtaaggaa gaggggaaga gaaaaggaaa ggaggctgaa 64620
gaggaaccaa agcccaggat tctctagaaa tgcgtcatcc tccagagtat gggagcacat 64680
tgggtcccag caacctcagc gggacctact tctcagaaac acaagagtgt ccaatggatg 64740
aaacctcagc tgaaaacata taaatgtcca aagacattgc agggtctggg aggaacaaag 64800
tatgataagg ttgttaacta tcacggactc agcaggatct gggggcatca ccagtggggt 64860
tcctctccca ctaccttcaa taacccaggt gaagaagcag gggcagcaga gtaagattta 64920
attatgggtt acgctgtggc tggcaatatc ccaggagaaa aaagagtaaa ctaagctatg 64980
tttagggatg catgcttata tagtaaaatg ctaaagaaga aaaaaaataa aagaagcatt 65040
ccacatgaaa gtcagataag tggttacact taaggggagg aaggtggttt taactgtgca 65100
actgggaggg gcacaaaagg aggcttccgg ggtaccagaa atatttttct ttcttgatct 65160
ggggagtaca cataattcat aattcactaa gccatgcatt tttgtgtttt gaacttttag 65220
gaatatgata tatttcaaaa tttaaaaaga aaaaactaaa atatgctgag atacatgaaa 65280
cttcaactat agaaggacaa ggcaaggtaa ggcactgagt aagggctgag cgagggtgga 65340
aggcaagatc actaaaaaaa agaagttgct actgggtcag ctggaaggag cgtctacaaa 65400
agaatcttaa tagtattccc tatatcatta atgaagacaa taatccacag gtatcagcag 65460
tagctgtctt tattaccaat agacagcatt aaaaatgttg acattaccat tcttgcagat 65520
aacctggatt tatattcatc aattcattga actaatcaat tttaaaatta aggccaggcg 65580
tggtggctca cacctgtaat cccaccactt tgggaggccg aggtgggcag atcacctgag 65640
gttgggagtt ctcgagacca gcctggccaa tatggcgaaa tcccatctct actaaagata 65700
caaaaattag ccaggtacga tggcatgcgt ctgtagtccc agctactcga gagactgagg 65760
cagagagaat tgcttgaacc caggaggtgg aggctgcagt gagtcgaaat tgcaccactg 65820
cactccagcc tgggcgacgc aaaattctgt ctcaaaaaaa aaaacagaaa aagaaaaaaa 65880
cttcagaatt aacatagttt ttaggccagg tgcggtgggt cacgcctgta attccagcac 65940
tttgggagga caaggcgggc agatcacttg aggtcaggag ttcaagacca gcctggtcaa 66000
cacagtgaaa ccccgtctct actaaaaata caaaaaatta gccaggcatg gtggcaggcg 66060
cctgtaatcc cagctactcg gaaagctgag gcaggagaat tgcttgaacc caggagatgg 66120
agggtgcagt gagccgagat catgccactg cactccagcc tgggcaacag aatgaaactc 66180
tatctctaaa aaaaaaaaaa aaaaaaaaaa aatgctaagc ttttaagtcc ccaaggaata 66240
tggcaagact tgagtttgag agtcaggggc taatgttcaa aaatgaggat ccctcattct 66300
aaagatgtct gcatatctgc agtctcacca tttaaagaaa caggtggatt ctccttttaa 66360
caacagatct tcttttggat ccatcttttg agctttgcat ggatatgtgt gtacagattt 66420
gtgtggttat gtgtgggtac gggaaaatat aaatactaat tatctggatg acaaaattac 66480
atatggtttg tatttctttt ctttatgctt tctgaatttc ccaaattatc tagaacaaat 66540
cctatgcaat taacaaaagt taattgtttt tagtcttcta cctatataag gtacagcaag 66600
cattacgaca gcgtgtaaaa gacaagccta taactataaa ccactagatt gcttttacca 66660
gtcctaacaa ttctaaaatg agtagataat atttatttat ttatttattc attcatttat 66720
ttaaaaatta aggagacaaa catggtggct catgcctgta atcccagcac tttcgggagg 66780
ctgaagtagg aggatcacta gagcccagga gttcaagacc ccgtctctaa aaaaaaataa 66840
ctaaaaatta gctgggcctg gtggaatatg cctgtagttc cagcttgagc ccaggaggct 66900
gagtccgtga tgagccgtga tcacatcaat gcaatttata gcctgggcga cagagccaga 66960
ccctgtctca aaaacaaatt aataaaaaat aaaaaatact atatttagta aaccaacata 67020
ccaaaattaa gtatttctac aggttttgat ctaacacgtc cttttgataa atattttctt 67080
tatagcataa actgggcaaa tatataataa acttagtaag tagtaatagt aacaattcaa 67140
actcatccag tcaagtcaag caaagtgctc atttcacatc tcctaagttt ctggactggg 67200
aagccactaa cccattagat tttcctcaat ttcaattgcc tgaacaaagg aggcaggaag 67260
caaactacta cataaagtga actatagcta agtttattta ttcaacaaaa tttaacaatc 67320
taacattgaa gtccaaaact gaagttgaaa acagtttcct tgttccacag aggtacaaat 67380
tttaaagtac agtactgaag agtatcatac atttgaaagc ttacatattt atttagcaca 67440
ttcctcccca actttcccaa tcatgtctct taaaggtttt tacagcttgc ttccattgta 67500
agctgcctcc agaaatgtct cttaaaggtt tttacagctt gcttccattg taagctgcct 67560
ctagaaattt tttatttttt tggaaagaga tagagtttat aaaataattt ctacattaaa 67620
aatttcaggt tgggggcagt ggctcacgcc tgtaatccca gcacttaggg aggtcaaggc 67680
aggtgtccca cttgaggcca ggagtttgag accagcttgg ccaacacggc aaaaccctaa 67740
agtgcaaaaa ttagctgggc tcccttgtag cctcccagct acaagggagg ctgaggttgc 67800
agtgagctga gatcgtgtca ctgcactcca gcctaggcaa cagagcaaga ctccgtctca 67860
aaaatacata catacataca taatatttta taagtactac aatcaacctt aaagggaagt 67920
aaaacagtcc tttctctagt aagactcaac ctgtttggta ggatgaagac taccaaaaga 67980
aaaaagcagt acttatttct tgttaaaaca atgatagcat cctagggcgt atcagtagtt 68040
gcagatatga aaaatgaaag cataaatact ggaattatgc cacctaatgt ttctgggaca 68100
acgtttttaa aaaagtgaat agaggcgctt ggagactgtt agttttgaga aatgataaat 68160
aatagtattg aaactaaggt ggcaagtgcg ggttcagaaa cagtaaaata cctttttcat 68220
tttttacaaa ttatttttat acccttaatt ctgtacatat cgatgaacca cctcatcttt 68280
gctatatgct tactcacaca aaatggaatt aacatcttgg ctctcctaaa aaagtctttg 68340
ttcccagaca gaggttccca gagagagatt agcaaacaaa aattggcaat tgactgctat 68400
tctatattaa tcacaagccg atcacaagtt agagtctctg agcattataa tgtttactcc 68460
tcagtaaaaa tattaccttt atgttccaca taaggctcca tatccaaaat ttctgagaag 68520
ccaatgtagg tattcagctt tttcttatgt ccagtttgcc taaccaagag gaaagctgat 68580
tatatttaca tttaaaacaa tcataataca atatataagc tctattagct attttaataa 68640
actcaacagt agctagcttt cacttcacaa tcttcctcca aaacatgtac aattagaagt 68700
aaacagaata ttgttttata gctggacaaa tatgaggtta aaaaatgtga atgcgaagtg 68760
ctgattccaa acacagctta ttttccagaa gtttcaactt aatcacaaaa cagattatcc 68820
tgctttacag aagacatgca catgtgcaaa cattgccttg attttaatta taaaatgaaa 68880
aatacattcc catggcgggg gtgtaatgag tacaaaattt attctattta aaataaagga 68940
caatacagaa ggtcagggta attcaattac ttgcagtttt tctttctttt tttttttcca 69000
agacagagtt tcactcttgt tgcccaggcc ggagtacaat ggtgcaatct cggctcactg 69060
caacctccgc ctcctgggtt caagtgattc tcctgcctca gcctccccag tagctgggat 69120
tacaggcgcc tgccaccacg cccggctaat ttttgtattt ttagtagaga cggggtttca 69180
ccatgttggc ccggctgatc tcgaactcct gacctcaggt gatccacctg cctcagcctc 69240
ccaaagtgct gggattacag gcgtgagcca ccgcacccgg cccttgcagt ttttaatact 69300
ttcttagaat aaaaaaagta aggatttttt acttttctag ttatcattta tatatggttg 69360
gcttctttaa aattttttat gataaaatca tgaaatatcg acatttcaaa atgacagcct 69420
ccatctataa ctttcatcct caaatctaga gtttcaaatt acaaccattt tatcatctca 69480
tctatggtaa agtctgtaca tagtagacca caatgaacaa caaacactaa tatttgcaca 69540
catttacctg tcaaagacaa aacgcattag ctgcaagttc agagtgcaag gaaggctaag 69600
aagtcgaatc tttcttgttg cattctgttt gctttgacag ttctcgcaaa aatagcgatt 69660
gtctccttct aatttttctt cctgatcaag aataagacat attaatttta aaaagaagat 69720
gggtttaaaa caagtgataa aacccttgat gtaaagtata atttcatttc agttaatagc 69780
tctcacttaa gctacttaaa aacagctact ataaataatg gacacacaaa agtaatggga 69840
actgttcagc agtgacatta tcaatttgaa tacactgata tttaaaactg atgtgcctat 69900
ttcccaaatg tatgatatta aaaatacttg ttttaggttc tttgtcctgg taatcccact 69960
tctgggaatt ctaaagtaag ttttaaaaag aaatgtcaca tgtattttga tgcaacattc 70020
atttaaagac agcaaaaagg ctgggcaaca tggctcacgc ctgtaatccc aacactttgg 70080
gaggccgagg tgggtggatc acttgaggcc aggaattcga gaccggcctg gctgcccagg 70140
tgaaaccccg tctctactaa aaatacaaaa attagccagg catggtggta cacacctgtg 70200
gtcccaacta ctcgggaggc tgagacacaa gaatcacttg aacccgggag gtggagcttg 70260
cagtaagctg agatcacacc tctgcactcc agcctggaaa caaagcgaga ctctgtctca 70320
aaaaaatgaa gaaaaaaaca ggagggagga gggtagtgta aaaacgatat atgggcacca 70380
gaatacaaaa ttatatacat atttgtttaa aattactgaa acatattcat gagacaaagc 70440
taaaaagaga cgtgtagaaa aatcaaacat tttagctgat agtggtttct ttttaaaatt 70500
tgcctttata tttctataaa gctaattgca gccaatcata gctaaccgaa gactcaaact 70560
cctgagctca agcttttgta ccatattgta cttaccatat tgtaagtaat gcaatactgg 70620
taccatcatc tcttcacttg gcttccagga taccacactc actgacttgc ctcctaattc 70680
actggcattc ctccagggac tcctgtgcca gctgctccta cctccctgat ccctaacatt 70740
tgaatgtccc aggcctcagt ccttgtctct ctcccactcc cttggggatt ttatccagcc 70800
acgacttctt cctggaacta tacctctcaa acgtaacatg ctcaaagcca aactcctaat 70860
tcctctcaac cctgctcctc ccaggtcctc cctatctcag ttagagcaac tccattcttt 70920
cagttgatca ggccaaaaac cttagtaatc cttgactccc ctcttactct tactctccac 70980
atccagtctg caaattaaaa aaaaattttt ttttcattat tttattttta cagacagggt 71040
cttgctctgt caccaaggct ggggtgcagt ggtccaatca tagctaacta cagcctcaaa 71100
ctcctgagct caggcaattc tccagcctca gcctcctgag tagctgggat tatggctgtt 71160
caacaccaag cctggttaat ttttttattt tttgcaaaga cggtctatca ctatgttgcc 71220
taggctggtt tcaaactact gttctcaaat gatcctactg tctcagtctc ataaagtgct 71280
gggattatag acatgagcca ccacatctgg ctccggcctg caaattttat ctgctcttag 71340
aaaatatatc taaaagccaa atggtgctta tcacctcttc agttaccccg tggtccaaga 71400
caccatgcac tcccatctgc cctcaatcca tcttcagcct attctcagca cccatagtta 71460
tcccttaaaa cagactgtac cactcctacg catatgaccc tgatgccatc tcaacctcac 71520
acagagtaaa agtcaaactt ctgacaaagg tttactaggc cctctctgat atggcccttg 71580
tgtcacctcc acgactttat cttctatcat ttactcactt cggccacact aaccgccccc 71640
cacccaggct gttcctcaat ccaccaggca agacacattc tcattttggg ctctgcactt 71700
gctgtttcat ctacccagaa cactcttctc cttgtttcta acggggctca ccccttcacc 71760
ttcaatcatt ttatttcaaa ctccaccgac tccagcctac tccccagcac attgcccagc 71820
gccacattcc ctgctttctt cttctccaca gcccttattg tagttgaccc actatatatt 71880
cgcactttat tttactgtcc ctcccttgtg cctacaccac tactttgtag gctccataaa 71940
ggctaatccc caacagctga aacactgcct gacacagtaa gcattcaata aatattcatt 72000
ggccaggcgc ggtggttcac gtgtgtaatc ccagcacttt gggaggccaa ggcaggcgga 72060
tcacctgagg ttgggagttt gagaccagcc tgaccgacat ggtaaaaccc tgtttctact 72120
aaaaatacac acacaaaaaa aattagccag gtatggtggc ccgcgcctat aatcccagct 72180
actcaggagg ctgaggcagg agaatcgctt gaatccggga ggcggaggtt gcaatgagcc 72240
aagattgtgc cattgcattc cagcctgggc aacaagagag aaactccatc tcaaaaaaaa 72300
aaaaaaaatt cagcgaaatg aattcaatga ctacttcagg catgcccatg gatgagctga 72360
ggaagtaaga aagcacaaaa aatatctgaa gacagctagc tagctagcta gataataagc 72420
ttgtctatta cactatgtat acattcatgc ttgacaacaa agggttcctc ttagcagttt 72480
tccactcaga acagaaagga atcactgaat tatctccaca tgaatctaaa tatacagaaa 72540
gcagaatgac catatcaatg taaaaaagtt tcatatttag cacattctcg ttttcattag 72600
acaacaaggt aaaatacctt tatgataact cagcatagag ttctttcaat accccactac 72660
ccacaatcac agaataatat cttctcacac atacataact ttacatataa aataacttga 72720
aataagcaaa attattttta agacacaggc tgctttggta cttcataaag tgtcttctgg 72780
atcattacag atgcttctta tgtagaaaaa gctgacacaa taaaagctct agccactaaa 72840
tcaaaacaga atagcattca gaacagcatt taactgttaa tgggcaggaa caatacatac 72900
accaaaattt gaataccttc aaaaattccg agatacaatc tgttaactgt ttgtggcctt 72960
ggatatttaa ctccagctca taaaattttg acaaaagctt agactctctg ccacactggt 73020
tgcaactata ataaaacaga acgacaaaat tcagatcaga gtgtgaaaag caacaaagtt 73080
atattgtatt acatcctaga aagatggaaa aaagcattta taactttcat tagttctcct 73140
tcacagaaat tatgtatact aaaaatgaaa tataatccca gcattttggg agaccaaggc 73200
gagtggatca caaggtcagg aattcgagac cagcctgacc aacacggtga aaccccatct 73260
ctactaaaaa tacaaaaatc agccggatgt ggtggcgcgt tcctgtaatc tcagctactc 73320
gggaggctga ggcaggagaa tcgcttgaac ctgggaggca gaggttgcag tgagccaaga 73380
tcacgccact gcactcatcc tgggcaacag agcaagagtc catctcaaaa aaaaaaaaaa 73440
aaagaaaaga aataaaaaca aagtgcctgg tgaagctaaa cattcgttgg gaaactttct 73500
taaaataaat gttaagaggt acaagtgcag ttttgttaca tgaatatatc gcactgtggt 73560
gaagtctagg ttttaatgta accatcaccc aaatgttgta tattgtactc atgcacattt 73620
ttttaacagg cattttacat ttacttttag tattctagcc agttccaatc ttactcttta 73680
gctcacacca cacagccata aagcaagagc agactgcaag agctcaccca gacaccgttc 73740
ctaacacctg gatgggtgca actgcaatta ccaactcact tgtttatatg ttcccatgga 73800
aatgtattac tataaatatt tcaggtccca tgataaacca ctaaagctac aacctggaac 73860
tgcactgaaa aatagttaac atatgagcaa ctgtcttaga ataaaatgta ccatgaaaaa 73920
gttgaaacag acttacacag ttacataggc atattctcca cagaactgct gttgaacaat 73980
attgcgcaca tctggattct tttgtttaga caaagtatct tccaatagag acataaagag 74040
ctttgaaaat tcttgagcat cctacaagtt taggttaatg aaaagaaaaa tcatatcttg 74100
cttttcaact tctactacaa atagtaatac attcaacatt ccagaaacta cctatacttt 74160
caacttagca ttttcaaaca ggggctacag ctatgttcaa tcagtttgtg cccccatatg 74220
aatttccata aatggaatca agtataatgt gtaaactatt ggacagtaaa taaaggtttt 74280
cattcaaaat agaaaaaatt taatttttaa aaagcattct acttcatctc cctttataaa 74340
catgcttagg atgtttgggt acctctgaat atttaaaaaa aaaaaaaaat tcagttctta 74400
cctgctgttg tccagtgtcc aggcccaagg ctttaacaaa tcctgatgga tcaatgtatc 74460
gcctattact gttttgcaac aaggcaaaca agtactggag atgctcacaa attgtttgag 74520
gctcataatc tattaaaaca aaaatataga tttggggttt tttaaggtgc tacttttctt 74580
tccaaaaaat ggtacttcct cttcacatga gaacataaac atctctacat ccaaactaga 74640
ttaatacttt attatcattt taaaacttta aaagaaatag gctgagcacg gtggctcatg 74700
cctgtaaccc cagcactttg ggaggccaaa gcaggcagat cacttgagat cagaagcttg 74760
agacaagcct ggccaatatg gagaaacccc gtctccacta aaaaaaatac aaatattagc 74820
cgggtgtggt ggtgcacaca tgtaatccca gctacttggg aggctgagac acgagcatct 74880
attgagcgcg ggaggaagag gctgcagtga ggtgagatcg ccaacaaagt gagactctca 74940
aaaacaaaaa acaaggctgg gcacggtggc tcacactcgt aatccccgca ctttgggagg 75000
cagaggcggg cgaataatct gaggtcagga gttcaagacc agcctggcca acatggtaaa 75060
accctgtctc tactaaaaat acaaaaagta gctgggtgtg gtggcgagca cctgtaatcc 75120
ctgctacttg ggaggctggg gttcaaggat agcttgaacc caggaggtgg aggttgtggt 75180
gagcagagat catgccactg cactccagcc tggatgacag agcgagactc tttaaaaaaa 75240
aaaaaaaaaa aaaaaaaact ttaaaagaca gggctggcgc agtggctcaa ggctggaagc 75300
agtggttcac gcctgtaatc ccagcacttt gggaggccat ggctggcgga tcacaaggtc 75360
gggagttcca gaccagcctg gccaacatgg cgaaaccccg tctctattaa aaatacaaaa 75420
attagtgggg catggtagta cacgcctgta atcccagcta ctcgggaggc tgaggcagga 75480
gaatcacttg aacccgacag gcggaggttg tagttagcca agattgtgcc actgcactcc 75540
agcctgggca acagagtgag actccatctg ggaggaaaaa aaaaaagaaa tagaattagc 75600
aaccatgttt tgtggaagtc atgaggcagc caggactgtc catatacact ccccaaaggc 75660
aagagcctac ctgtattaaa gcaacaacag caatcatgac tacagtgtct agtcatgatt 75720
ttttaaagtc cagttaatgt ggacttggga tctcaagcac agcaattcac acttaagtga 75780
agaatacaaa accgtagaat tttagagttg aaagttttaa tgagctagtg cagggaatgg 75840
aagcagaaag catggatatt gagagcccag aagacagaag tcttatcttc tttaagttat 75900
taacttattg cttctcagct ccaaatctac ccttctttgc ctgctcagtg atgagagatg 75960
ggctctgcaa atacttctcc tttgccagtt atcaagaagg taaggcttct cagtgaaggg 76020
cactgcaggg tttggttgtg cctctgtcac cagcctgctg cagatcagct tcctccaggg 76080
ctccaggttc ctgcccctaa cagtagtcag cagcttaccc agcacctctt ctgatagctt 76140
cacagtacag tgcctccagt gaggcatttc ctctcgaatg accaccctgt gaatggcctc 76200
ccggacactc tctcaggtga ctctgtaggg ggttccaggg cccagcacct tctcatggac 76260
agtttctagt agggattccc agggaggcat ctcagcacct tttcagccac ccagtgcatc 76320
ccagcagtgt ccaaagaggt ctggatctca agcctgggcc atgggggtga cagactatcc 76380
gttggatgtt ctctttcagc cccagggata caggttgttc cctgtatctg ctgtccttgt 76440
attctttaaa atcctcttta atctttaact cttattaatc aattcctcat ttctctaatt 76500
aattctgtta ttaattctca actttccctt ttcaaattat tctgtagctt ctgtcttcta 76560
actggactat atttatctcc ttactaccaa ctgtggcttt cagcaagtca atatatcatc 76620
ttcaaaataa agataaaata ttactccttg gcctgcaaaa gcattgcagg ccagtaaaag 76680
ctattcaagg ccaggtgctg tggctcatgc ctgtaatccc agcactctgg gagaccaagg 76740
aaggtggatc gattgaaccc aggagtttga gaccagcctg ggcaacatgg taaaatgctg 76800
tctccaaaaa aaacacaaaa attagcaaga ggtggtggtg catgcctgta gttccaacta 76860
ctcggggggg ctctggcagg aggattgctt gagcctggga ggttgaggct acagtgagct 76920
gtgctcgcac cagcctgggc gaaaaagtga gatcttgtct caaaaaacaa acaaacaata 76980
aaaaaaaacc ttttctgttc aaattattgt gtagcttctg tcttctaatc agactctgaa 77040
tatttgtatc cttactacca attgtggctt tcagcaagtc aatataccat ctgtaaaata 77100
aagataaaat attactcctt ggggtgcaaa ggttttgcag gctggtaaaa gctattcaag 77160
gcctggcacc atggttcatg cctgtaatcc agcacttttg gagaccgaga caggaggact 77220
gcttaaggcc agaagttcaa gaccagcctg ggcaacagag caagacactg tctctataaa 77280
aaaaataagt ttaggccagg cacagtggct cacacctgta atcccagcac tctgggaagc 77340
cgaggcgggt ggatcacctg aggtcgggag ttcaagacca gcctgaccaa catggagaaa 77400
ccccgtctct actaaaaata caaaattagc cgggcgtggt ggtgcacgcc tgtaatccca 77460
gctactcggg aggctgaggc aggagaattg cttgaacctg agaggcggag gttgtggtga 77520
accgagattg tgccattgca ctagagcgtg ggcaacaagt gtgaaactgt cttaaaaaaa 77580
taataataat aataataaaa taagtttagg ctagacacag tggctcacac ctgtagtcgc 77640
agcactttgg aaggccgagg cagccacatc acttgaggtc aggagttcga gactagcctg 77700
gccaacatag tgaaacgctg tctctactaa aaatacaaaa actagccagg cgtggtggcg 77760
ggcgcctgta atcccagctt ctcaagaggc tgaggcagga gaatcgcttc agcccaggag 77820
gcagacgttg cagtgaaccg agatggcgcc acttcactct ggcttgggaa acagaggaag 77880
actcaaaaaa aaaaaaaaaa aaaagtttaa aaaaatgttc aggaagagag ctctccccca 77940
cccctttcca cccacctttt tcttcttgga tgccgtctcc cagcatgtag tcactacaag 78000
tgcttggaca taagtagagt gcctgccgaa gctccaagtt gagaaaccac acttgaagaa 78060
atgtgttgac ataacaagtg gctccaaggt tagtcaggcc cacaaatgag ttctacaaaa 78120
atacaaaatt cataattata aaacccattt tcctttaaac aaccaatttc taagcattat 78180
tcttaaattt tcagattaaa aatgtgtaag accgtcacaa ccaacatggt atagccacct 78240
taagtttctc ttggctggag gtggggcata attttcatga aagccccatt ttgggttgac 78300
cacaggagtg aaaaagactt cggacggcat cactgctcat ctctagcata tcgtcttctc 78360
cagccactta aatctaaaat tagaacagtg gattctagaa aagatcggtt ttgaacaagc 78420
gtatataggt tttatgtttt ctgtatttct aaactgccag cattcagcag aatgacaaag 78480
taaaacttat gcagaaaact tcctttatat tctagagatt ttaaagattg gcggtggtag 78540
agggaactgg ctgcaacttt ttccaaagat aaggttggga attcctgacc ttacaaagaa 78600
ttattatttt attaaaatat ctatatataa caaacttgga tatttcgtga atgctaagat 78660
ttatgtctag aaaatttaat gtatattttt aaaaagcaaa attatatata aaatacaagc 78720
cctagaaagc aaagtgctat catcatgagt ttgttccctt gaattaccat ctcctttaaa 78780
gaggcgttaa gatttcaaaa taaaacatgc aatgttaaag caaacataga atcagcattc 78840
aaactaaaac tattatttaa aggcttactg aattacgcag ctgcctgttt taaagcatat 78900
cattaagaag tgttccaatt caagtggctt agagtcttaa gttctactgc ttatcttaaa 78960
gctgcacagg ttacctgaaa tcagtagagt tttctgatca caggcccaaa acaaaagcaa 79020
aaacaaaaac aaaaaacagc atatagcaat cgcttaaaaa atgatggttt accttttttc 79080
tcctctcaca gttgggatca tcgatgttat gaaaactatt ttcatctatt tctcctaacc 79140
aaatatgctc accaatacca accaagcaat tcggatttcc tttgcagttt cgtctaaggg 79200
gaaaaaaaaa acctttaatt tttaaaagac catagtttca tgagagacaa acaaattaaa 79260
actaaaatga gataccactt ctcatctata aattagcaaa actgagaaag tataagacac 79320
tcagtttgtg agggtgtgga gaagaaagca tgcatatact gctggtagaa atgcagtcac 79380
taacaaaact acatagacaa ctacctttag acctagcaat ctcatttctg aggatttact 79440
gttccttagg ctatacctcc aacaatgcaa aatctcactc ataaggttat tcattacagc 79500
actgtctgtt aattgcaaaa tattggaagc cacccaaatg cccaaaaata gacaatatgg 79560
tacatctata tggcagagta ctatgcaact gtaaaacaca cacacacaca cacacacaca 79620
cacacacaca cacagcatga aaaagatatc tatgaacaga tataaggtaa tttataaatc 79680
caggacacat tattaagtaa aaaaagcaaa atgcaaagga gtatctctag tatactgtta 79740
tgtgtaagaa atatataagg aaaatataca tgtacatatt tctgctcatt ttgtacaaaa 79800
agaaatacag aaaggaaaaa caagagacta atgaaattgg ttacctacag agcatgagtg 79860
ggaataaggt taaaagaaaa tacacctttt cggccggaca cagtggctca cacctgcaat 79920
cccagcactt tgggaggctg aggcaggcgg ataacaaggt caggagttcg agaccagcct 79980
gaaaccctgt ctctactaaa aatacaaaaa ttagccgggc gtggcggtgc gggcctgtaa 80040
tcccagctac ttgggaggtt gtggcagaag aatcccttga acccaggaca cggaggttgc 80100
agggagccga gattacacca ctgcactctg gcctgggcga cagagcaaga ctctgtcttg 80160
gaaaaaatga atgaatgaat gaatgaatga atgaatgaat gaaaaggaaa tgtacctttt 80220
catataatga acaatttggg accatgtgac tgtttctcac actacttcac gcatgcacac 80280
aaacaaaaat aaatcaactg gctaggcgtg gtggttcacg cctgtaatcc tagccctttg 80340
ggaggccaag gcaggaggat cacttgaggt taggagtttt gagaccagcc tggccaacat 80400
ggtgaaaccc tgtctctact agaaatacaa aaattagcca ggtgtggtgg tacacgtttg 80460
taactccagc tacaggctga agactggagg ctgatgcagg agaattgctt gaacccagga 80520
ggcggaggtt gcagtgagcc aagatcgtgc cactgcactc cagcctgggc aacagagaga 80580
gacacggtct caaaaaaaaa aaaaaaaaaa aaaaaggaat caacaaggat gacaggaacc 80640
ctaaattcaa aacagagaaa acatatttca actaaataaa agatccagac tgaagggaag 80700
gcaggagtgg gggagggaga gggagggggt gtgactgacc aaagtaactt aaacagttat 80760
caagctcatt tactagtacc ctctggctaa agacaaaagg aacaaacagc caactctaat 80820
tagtaggctt cttttccata gagacatggg ttaataattc tgaaacacag atcctgactt 80880
ctaaatatta cccactaaaa gaatcccgtg ctccttggag aaataactgg ctgattccaa 80940
ggccagggca gtgaaattag aaaacgaacc tacatcttac tgtgccctaa aatgatgtac 81000
tgaaagatgg tggagacatg tcaaaagagc acaagagttg gctggaaggg gaggtcccac 81060
tggtcaaatt tggcaacaaa atttagcaac aaaatgagta ataggattat aacctactga 81120
ataaagtaag aatccatcat ttcatggtga gatggatgga agaaaaatct cttcccttta 81180
gaagaaaacc aactatcaaa gtggaaggaa tgacagaatt aaaaatctcc atttggcata 81240
catcagattc agaaaggaat gaggcaagga tcatcacgga tgctaacgta ggcaagttgg 81300
agaaataaca atatttacaa tgtctcaaag tatctcagaa aaagttaatt acaaagggaa 81360
agataataac tttcagtgga gaaacttgac agacaccacc ttaaccaaat gcttaaattt 81420
aacacaccca gtaatgaatc taattgacac cacacacctt ctggtataat gcacaacaca 81480
gaatcacttc tgtgatgttc tggccaaaga tgcatggcct taattgaatc atgaggaaac 81540
atcagaccaa accaactcaa gggactttat acaaaataag tcagtgtcat gaaatacaaa 81600
gaaagattca ctaacagttc cagattaaag gaaaccaaag agacacaact gaatgtaaca 81660
taagcttagg ttttcttttg ctataaagga acattacagg acaaagttct gcagatttct 81720
gtaggatacc cactaaagga ttactgataa cagtaaaaga ctggaaattt atatggaagt 81780
aacaaaataa attacaatat aaccaaacaa caaaaactac tgctgtcaaa aaataaaaag 81840
gtaggccggg cacagtggct cacgcctgta atcccagcat tttgggaggc ccaggtgggc 81900
ggatcacaaa gtcaggagtt cgagaccagc ctggccaaca tggtaaaacc ccatctctac 81960
taaaaataca aaaattcgcc aggagtggtg gcgggagcct gtaatcccag ctacccagga 82020
ggctgaggca ggagaaatca cttgaaactg gaaggcggga gggtgcagtg agccgagatc 82080
gtgccactgc actccagcct gggcaacaag aacaaaactc tatctcaaaa aaaataaaaa 82140
taaaaataaa tttaaaaaaa ggtagggaaa gcttttaatg ttgtgatata taacgatatc 82200
attagttgaa aaaaggaagg tgggccaggc acagtggctc acgcctgtaa tcccagcact 82260
ttgggaggct gaggcaggcg atcacctgag gtcgggattt cgagaccagc ctgaccaaca 82320
tggagaaacc ctgtctctac taaaaataca aaattagccg ggcatggtgg cgcatgcctg 82380
ttaatcccag ctagttggga ggctgaggca ggagaactgc ttgagcccag cagggtgaag 82440
gttgtggtga gccaagatca cgccatcgca ctccagcctg gacaacaagt ggaaactttg 82500
tctcaaaaga aaaaaaagaa aaaaaaaaag gaaggtacaa aacactgcat atcatgttgc 82560
catgtttttt atttacaaat ggggtaaaca cacccgtttg tttagataga agagtacatt 82620
ataaactgga aacaacctta tcggcaaaga ttatctctgt acttgccagc tataagtcag 82680
aagtaaataa cactctgaac ttcctttttt ttttttttga gactcccata ctgaagtggc 82740
atgttcatgg ctcactgcag cctctacatc ctggactcaa gtaatcctcc agcctcagcc 82800
tctggagtag ctgggaggtg catgccacca tacttggata attttttatt ttattttttg 82860
taaaaacagg gtcttgccat gttgccccag gctgacccca tcacttttta tacctttcag 82920
actttgaaca ataaaatgtg ttacatattc caaaaataag taaataattg ttttaatgtt 82980
cagtttaaac atactgtctt ctaaaatata aaaatgaagc tgggtgtggt ggcacatgct 83040
tatagtgcca gctattcaga aggctcaggc agaagatggc ctaagcctag gagttggagg 83100
ctgcaatgaa ctatgattgc acctgtgaac agccactgca ctacagcctg gccaacaaag 83160
tgagaccctg tctctatttt aaaacttttg aaaaaataaa aatgaaaaca agttcgacca 83220
atttaagaac agttttgtca gcttatatca aagctaggag ggaaaaaagc ttattaatga 83280
aataaagtag aacccatcca ctgtggggag aagaagctag ggttttgttt tagtgcttat 83340
aactcatctc taatgggaaa ggtctactat aagagagtta aagaaacaaa actggccggg 83400
tgcagtggct cctgcctgta atccccagca ctttgggaga ctgaggtggg cagatcactt 83460
gaggccagaa gttcaagacc agcctggcca acatggcaaa accccgtctc tactaaaaat 83520
acaaaaatgt gccaagcgtg gtggcgtgtg cctataatcc cagctacttg ggaggctgaa 83580
gtgagagaac cgcttgaacc aggaaggcag ggtttgcagt gagctgtgat cgcaccagtg 83640
cattccagcc aggctgggca acagagcgag actcgtctca aaaaaaaaaa gaagaaacaa 83700
aactgattct gagactgaga aaagtaacag aaaatctctc ctgggaacag tgacaaggat 83760
atactaggaa ggttctttcg aaagaaaatt acagctagtg gcaatggact ctcccaaagg 83820
tctttggcag ataggaaaaa atagtgtcag taaccatggt gaaaatatac ctctaaaaca 83880
aagtaggcac ttattttgtc aatcctttca actctgcttt tcaaaggtgt aatatcaagt 83940
cttgtttgtt cactccctcc tcttggacaa gtgggtggta aaaatttttc acacgggccg 84000
ggcgcggtgg ctcacgcctg taatcccagc actttgggag gcggaggcgg gtggatcacg 84060
aggtcagggg tttgagacca gcctgaccaa catggtgaaa ccccatctct actaaaaata 84120
caaaaattag ctggacgtgg tggcaggcgc ctgtaatcct ggctactcag gaggctgagg 84180
caggagaatt gcttgaacct gggaggcgga ggttgcagtg agccgagatc acgccactgc 84240
actccagcct gggcgacaga gcgagacttc atctcaaaaa aaaaaaaaaa aaaaaaaatt 84300
cacacgacct ggctggggaa acagatactc ccatgtgtca aacacagaca tcattctcag 84360
aaaatagttc cactggatct gtttagattt tagtctccag ttcctgatag caaaataatt 84420
cagacaatga agaaaaggta ggctctccct gtccccaccc aaaaatcatg catactcaac 84480
tggttctaaa gctggcatca aaaggcaaac acaacctatg gcctaaatat taccacaata 84540
agactttcaa aagctactat gagaagctgg gagcaatctg tattattagg ccccacaaca 84600
ctggcattgt tctttttaaa ttttcttaaa ttaattgctt gctaggtatc actgaatacg 84660
tcttcagtcg gctagaacac caccacagca gaatgccaag tgcaggtgac ctgtgataga 84720
ctaccacccc aggccaaacc tatggctccc gagcctctat ggccacactt caggtgggaa 84780
ccaaaaagcc aatggcggtg ctttgcatta aaagggcttg ggctttctaa acttctaaat 84840
tgttgctaag cctttcatac atagcccaat atgggggggc ggggttgtgt ttgttctctt 84900
acttggagag gtaaagaatc tacttaacaa acacaaataa cagctgggcg cagtggctca 84960
cgcctataat cccaacactt tgagaggcca aggcgggcag atcacctgag gtcgggagtt 85020
cgagaccagc ctggctgaca tagagaaacc tcgtctctac taaaaataca aaaaattagc 85080
caggcgtggt ggcacatgcc tgtaattcca gctactcagg aggctgaggc aggagaatca 85140
cttgaaccca ggaggcagag ggtgcggtga gccgagatca tgccattgca ctccaaccct 85200
ggtaactaga gagaaactct gtttcaagaa aaggaaggga ggaaggaagg gagggaggga 85260
gggaggacgg atggacaggc agacacaaat cacagttcta attataagct gttacttcta 85320
aagccagcct tagcagcaca gcagaatgcc aaccacagag ggctgtagcc tctcccattc 85380
gtcattctcc aatgccccta actccatttt atccctcctt aggagtaggc cccaggtatc 85440
aaggatcatt tatcatcatg tgtgtgccaa tttccttaca gtagaaaaac agttatgtgt 85500
acctgtgtct atcaactatc aaaacagatc aaggaggttg agtgtttcac aaaatatgag 85560
acagtgtctg ggagcagtgg ttcacacctg tagtcccagc aatttgcaag gctgaggcag 85620
gcagatcact tgaggccagg aatttgacac cagccaggcc aatatggcga aaacccatct 85680
ttactaaaaa tacaaaaaat tagccaggtg tggtggcata tgcctatagt cccagctgct 85740
caggaagctg agacaagaga attgcttgaa cccgggaggc agaggctgca gtgagctgag 85800
atcacgccac tgcactccag cctgggcatc agagagagac cctgtctcca aaaaaaaaaa 85860
aaagcctggg cgcagtggga ggccgaggct ggtggattat gaggtcagga gttcaagacc 85920
aacctggcca agatggtgaa accctgactc tactaaaaat acaaaactta gccaggtatg 85980
gtggcaggtg cttgtaatcc cagctactct ggaggctgag gcagagaact gcttgaaccc 86040
gggaggcgga ggttgcagtg agccgagatc gtgattgtgc caccccacac cagcctgggt 86100
gacagagtgg cactccgtct caaaaaaaaa aaaaaaaaaa gacttgatta cataggcatg 86160
actgattgaa tcactggcca ctggagatta gcaaccttta gtcctctccc ctcccagagg 86220
tcagactaaa aagttctaaa cctctcatcg tggttggttc tcctggcaac cagcccatgt 86280
ggaggctacc aagagctccc agccatcagt catttcatta gcatacaaaa agacacttag 86340
tcacttcaga gatcccaaag gttttaggag ctgtgccaga agtagtacaa agactaagca 86400
tatatttctt ataaatcaaa atatcatata accctgcagg aaaaataact aaagaaaaca 86460
tctcaaaaat gttaaatgac aacaatgttt ttgtttcaat aattctactt ctgggcacag 86520
gtccaccaaa cttgagtaat aacagcacaa tggcaatgcc atagtacgat aaggaattca 86580
gataatttaa tgggtacttt gttccaagac tgcactgtat gagaacacca acgtgttagg 86640
cagaggatag gttccaaaag gtttggttat gacgtactaa gcagacatct gctgtgattt 86700
taggccaggg acacactttg gcagcagtaa acaggacaga ccgggcgggg tgtggtagct 86760
catgcctgta atcccagcat tttgggaggt cgaggcaggc ggatcacttg aggtcaggag 86820
tttgagacca gcctggctaa tatggtgaaa ccccgttctc tactaaaaat tcaaaaatgt 86880
gccaggcatg gtggcacgcg cctgtagtcc cacctactcc agagactgag gcagaaggct 86940
cgcttgaacc cgggaggcgg aggttgcagt gagccgagat cacgccactg cactcaagtc 87000
tgggtgacag agcgagactc tgtcaaaaaa aaaaaggggg ggacagcccg aagctgaaca 87060
aggcatgaga cgttccgaag ctaaacaagg tgtgagacat aactaacaat ttttctagtg 87120
gaagatgagg tcttaaaaag ccaatttagg ccgggtgtgg tggctcacac ccgtaatcct 87180
agccctttgg aaggctgagg tgagtggatc acctgagaca ggagaatagt ttgaaactac 87240
gaagccgagg ttgcagttag ccgagatccc atggtgctcc ggcctgggca acaaagtgag 87300
actccatctc caaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaggc aattcagtgg 87360
gaataggaat ggaggaagtt caagcatatt gatgggaaga aatcaataga actggggact 87420
aataagatgc aacaggcaag aaaggaaagg agaaatctgg aatgatgccc aaaattgtaa 87480
caaaaagatt ttccaggctg gatgtggtgg ctcacacccg tagtcccagc actctgaaag 87540
gccgaggcgg gaggatcact tgaggctagg agttcaagac cagcctggcc aacgtggcaa 87600
aaccctacta aacttctact aagaatataa aaattagctg ggtttggtgg cgaatgcttg 87660
taatcccagc tactccagag gctgtcatga gaatcacttg aacccgggag gcggaggttg 87720
cagtgagctg agatcatggc actgcaccct agcctaggtg acacagcaca aaaaaaaaca 87780
atgttccaca agtcaaaaat tgtgttcagg gagtagaaaa gtagtaggct aggtatcaaa 87840
gggtatgaat gactaagttc cttctataat atattgacta taggtaggag atacactttc 87900
agttctgttt tggtagatct ccaatgatct gtcatttaag agtacacacg atgagtggaa 87960
aatttataat caaagatttc acagttgcta tgcagttcaa agattcatcc tttgaatggg 88020
aaagggggta gggatttcac tccaaatggt catttacaga ggttctgctt cttcctcatc 88080
acctcttagt ttcttagttt ttatttattt atttatgaga tggagtgtcg ttctgttgcc 88140
caggctggag tgcactgcaa cctctaccta acgggctcaa gacattctcc tgcccgagcc 88200
tcctgagact catgcctgta acccagcact ttgggaagct gagtcgagtg gataacttga 88260
ggtcaggagt tccagatcag cctggccaac atggcaaaac cccgtctcta ctacaaatac 88320
aaaaattagc cggcgtggtg gcgggcatct ataaacccag ctacttggga ggctgaggca 88380
ggagaatcgc ctgcacccag gaggcggagg ttgcagtgag ccaagatcat gccattgtac 88440
tccagcctgg gtgacagagc aagactctgc ctcaaaaaaa caaaaaacaa gaacaacaac 88500
aaacaaaatc catggcctcc tgggcactca gggtgtataa tactctactc ccaggctcag 88560
gtgatcttcc cacctcagcc ttccaaatag ctgggaccac aggcatacgc caccacaccc 88620
ggcttttttg tatcatttgt agagatgggg tttagcctca ttgcgcaagc tgggctagaa 88680
ttccttgact caggattata ggcatgagcc actgtgcctg ggaccttttt tatttttatt 88740
ttttgagacg gtgtctcgct ctgttgccca ggctagagtg cagtggtgca gtggctcaat 88800
ctcagctcac tgcaacctcc acctcctggt ttcaagtgat tctcctgcct cagcctcccg 88860
agtagctggg actccaggtg tgcgtcacca tgcccggcta atttttgtat ttttagtaga 88920
gatggagttt cactatgttg gccaggctgg tctcgatctc ctaacctcgt gacctgccca 88980
cctcggcctc ccaaagtgct gggattacag gcatgagcca ccgcgacccg gccaggactt 89040
tttagagagc tttttttttt tttctagaga cagggtctca ctacgttgcc tgcttacaaa 89100
taaattgttt ttaaagaaaa attttttgaa aaatcattga agaaggaaac tagtttactt 89160
aaaacactaa agtacagatt ttcctgaaag tgaaaataaa ggagaaccat gataatataa 89220
attctaggtt ctagttacta aaaactttac agtgattttc atgtaatgcc tcatggcatt 89280
actgtatcaa ggtctcataa attagacatg caagaaataa gcaaatctaa aaacaggtca 89340
ggcatggtgg ctcacgcctg caatcccagc actctgggag gccgaggcgg gtggatcaca 89400
aggtcaggag atcgagacca tcctggctaa catggtgaaa ccccgtctct actaaaaata 89460
taaaaaagta gccgggcatg gtggcgggta cctgtagtcc cagctactca ggaggctgag 89520
gcaggagaaa ggcgtgaagc tgggaggcag aggttgcagt gagctgagat tgcaccactg 89580
cactctagcc tgggcaacag aacaagactc cgtctcaaaa aaaaaaaaag agtttgcaaa 89640
atagaaaagt ctcagcaggt acctcactca actccaatat ggaaaaattc tccagcccta 89700
cagagactga gcagtgcatc aagtccctga ttgctatttt ccaggaggat gctggaaagg 89760
atgtcacaac cgcaaactct ccaagagggg agcccctcag tttcatgaat acagaactgg 89820
ctgccctcac acagaaccac aaggacgctg gtgtccttga ccacatgatg aagaaactag 89880
acctcaactg tgacaggcag ttagatttcc aagaattgct taatcttttt tgtttccctc 89940
atctcagact gaaaaatttc ttaatcttat tggcagcatg gccctagttc atcataagcc 90000
atgactgttt tatcatggct acctattccc agaagcaaat ctaaggaggg tcttgccttc 90060
aagccccacc cctttcaagc cccacccccc ctttccttct aggatctcag tcaccatctt 90120
ctcctcatgg ctcccataca ccctaagccc agcataccca ccacccgtgt aggccactcc 90180
tgctagtagt aataaaacag tatcgttttg gttttggttt gtgttttgag gcagggtctt 90240
gttctgttgc ccaggctgtg gtgcagcagt aaaatcatag ctcactgcag cctggtcttc 90300
ctggcctcaa gtgatcctcc cgtctttgcc tcccaaactg ctggggttac tagcttaagc 90360
cactgcactt ggcccaatat cattttttaa aacacacaca cagtctcgtc atgtatttaa 90420
ttttaagtat ttgtgttcgt tttccccatg tatgtctccc ttttgctttg agttgttgct 90480
tttgctaaca tcagacatgt tcatgattag cagtcattca atcctctgct actttgctaa 90540
agtcatagag atcaagtaac gtcaaattat tccatgatct tacttcccaa ctgatgagaa 90600
taatcaattc caggttgact gtagacctaa gcatgaaaga taaagcaata caacttatag 90660
aaataacaca ggagaatatt taggactctg gggaagataa atctttatct tatgggagct 90720
acatgatgag aacttctgaa cacaaagaga acttacgaac acaaagaaca atagacgttg 90780
gggtcttact tgggggtgga gggtgggagg agggagggga gcagaaacaa tttttttttt 90840
ttgaggcagg gtctcgctgt cacccaggct agagtacagt gccaagatct cagctcactg 90900
caacctccgc ctcctgggtt caagcaattc tcccacctca gcttcccaag tagctgggat 90960
tacaggcatg caccaccacg tctggctaat ttttgtatat ttatacagat gggttttcac 91020
catgttcccc aggctggtct tgaactcctg gcctcaagtg tccacctacc tcagcctccc 91080
aaaatgctgg gattaaaggc gtaagccact gcgccgggcc tacaaaaaaa ttttgaatta 91140
gccaaacatg gtggtgagta tctgcagtct cagctactgg ggaagctgaa gtggaaggac 91200
cacttagaca gaccccagag gccaaggctg cagtgaactg tgatcacatc atgtactcca 91260
gcctgggtga tgaagtgaaa tcctgtatca aaaagaaaag aaaaaaaagg acactaaaat 91320
atatatgcag aatgttcact gcagctttat tcataatgac caaatacatg gaaaaatcaa 91380
aatgaccatc actagtagaa aggaatataa tatatagtat atactcacac actgaaataa 91440
tgtacagcac tgttggtccc attggctcat gcttataatc ccagcacttt gggaggctga 91500
ggtgggcaga ttgcttgagc ccaggagttc cagactggcc tgggcaacat attgagacct 91560
cgtcctccac caaaaaaaaa aaaaaattgt acagcactag aattgaacac actactgctt 91620
acacataaat taatcttata aagttgagtg aaagaaaaca gaagcagaag gaatgacaat 91680
gtatgaatat acataaagtc caacataggc aaaataatct gctcaattca aagttaaggg 91740
taagtggttc ccttcaagga aaagaggcag aagtaactgg tagtagaaaa atggaagata 91800
agggtgtctt gaagtgttag taatgttttg atcttggtgg tagatatggg acagataaat 91860
ttcttttgtg ataattagtc aatcaagtgt cttttttttt tttttttttt gagacagagc 91920
tcactctgtt gcccaggctg gagtgcagag gcatgatctc agctcactgc aacctccgcc 91980
tcccaggttc aagcgattct cctgcctcag ccttctgagt agtgggacta caggcgcgca 92040
ccaccatgct cggctaattt tttgtatttt tagtacagac agggtttcac catattggcc 92100
agactggtct cgaactcctg acctcaggtg atccgcctgc atcggcctcc caaagtgctg 92160
agattacagg catgagccac tgcacctggc caatcaagtg ttattcttat gatttgtgtg 92220
cttttctgta tgtaaaaaaa taaattttca agctggctac agtggctcac gcctgtaatc 92280
ccagcactat gggacaccga ggcaggcaga tcacctgagg cccggagttg aagaccagcc 92340
tggccaagat ggtgaaaccc catctctact aaaaaataca aaaaaattag ccaggcatgg 92400
tggtgcatgc ctgtcatcca agctactaag atggctgagg cacaagaatc acttgaaccc 92460
aagaggtgga ggatgcagtg agctaagatc gtggcactgc actccagcct aggtgacaga 92520
gcaagactgt ctcaaaaaac aactaaaata caaataattt tttaagtaaa ttttcgaaat 92580
caagaccaac ctggccaacg tggtgaaacc ccgtctctac taaaaataca aaaagtagcc 92640
gggagtggtg gtgcacacct gtagtcccag ctacttggga ggctgaggca ggagaatcgc 92700
ctgaacccgg gagatggagg ctgaagtgag caaagatcgt gccactgcaa tctagcctgg 92760
gcgacagagc aagactccat ctcaaaaaaa aataaattat tattaattat taataaatta 92820
taatttataa ttattttata attttataat tataaattat aatataatgg ttaattataa 92880
attatttatt tatttatttt tcatgagaac catgagaaaa attctaaaag gaattaaggt 92940
cttgccttat cagatatttt tcaaatacta taaaataatt agaattgtgg tatcactaca 93000
gagttattca acgaaattaa tcaatggcaa aaaaaacagg gttgagaggc tgggtgcagt 93060
ggcttacacc tataatccca acactttggg aggcgaaggc aggcagatca cctgaggtcg 93120
acagttcaag aacagcctga ccaacacgga gaaaccccgt ctctactaaa aacacaaaat 93180
tagccgggcg tggtggcaca tgcctgtaat cccagctgtc agggggatga gacaggagaa 93240
tcgcttgaac ccaggaggtg gaagttgtgg tgagccgaga ttgcgccatt gcactccagc 93300
ctgggcaaca agagcgaaac tccatctcaa aaaaaaaaaa ggactgaaaa ataaacccaa 93360
gtaaatatgg gaatttgcca tgtaataaag gtggattttt aactggtgag gaaaaagact 93420
gaattgttca ataaatggtt taagacaagt gagtagccat ttggtaaaag gcaaaataaa 93480
atattgatgg atccctacct caatccataa atcaaattaa attataaaaa cataaaggtt 93540
gcataaaagt aaaccatcag tactaaaaca caacatgagt gaatattttt ataacctcag 93600
aattgggaaa tccagaaacc ataaaaaaag cattcataaa ttttaccaca taaaaaatca 93660
aaaactaacg taccaaaagg aaaaaaagcc cacaaagccc aaatatacca cagaaaatat 93720
cttcgacaga aatattcaat aaactaggcc gggccgggca tggtgggtca tgcctgtaat 93780
cccagcactt tgggaggccg aggcgggcag atcatgaggt caggagattg agaccatccc 93840
ggctaacaca gtgaaacccc gtctctacaa aaaatgcaaa aaattagctg ggcgtggtgg 93900
cgggcgcctg tagtcccagc tacttgggag gctgaggcag gagaacggtg tgaacccggg 93960
aggcggagct cgcagtgagc cgagatcgcg ccactgcact ccagcctggg tgacacagcg 94020
aggctccatc tcaaaaaaaa aaaaaactag gccaggcgtg gtggctcgcg cctataatcc 94080
cagcactttg agaggccaag gcaggtggat cacctgaggt caggtattca agaccagcct 94140
ggccaacatg gtgaaacccc gtctctactg aaaatacaaa tgttagccag gagtggtggc 94200
acggacctgt aatcccagct acttgggagg ctgaagcaaa agaatagctc gaatctggga 94260
ggcaaaggtt gcagtgagct gagatcacac cacagcactc cagcctggga aacagagcaa 94320
gactctgtct caaaaaaaaa aaaccaagaa agaaagaaag aaaaaaagaa agaaaaaaga 94380
aatattcggc cgggcgtgat ggctcacgcc tgtaatccaa cactttgaga ggctgaggca 94440
ggcggatcac atggtcagga gttcaagacc agcctggcca acatagtgaa acccctctct 94500
acaaaaatac aaaaattacc caggcatagt ggcaggcacc tgtagtctca gctacttggg 94560
aggctgaggc aggaaaatcg cttgaaccca ggaagcagag gttgcagcaa gctgagatca 94620
caccactgca ctccagcctg ggcaacagac tgagactcgg tctcaaaaaa aaaaaaaaaa 94680
aaaagaaaga aatattcaat aagctcttga aaatcagtaa gaaaatgacc aacaatccag 94740
aacacacaat tcacaggaga aatacaaatg gcaagtaaat ataaaaagga gaagggacac 94800
agtggctcac gcctgtaatc ccagcacttt gggaggccaa ggctgaggat ttcttgggcc 94860
caggagttca agaccggcct gggcaaaaca tgagatccta tctctataaa actaaaaaat 94920
aaaattaaaa agatgctcaa tgtcaccagc aaaaaatggc aaatgaaaat aagatgctat 94980
ttttcgctaa tcagatggaa gctgggaata gaaatgcttt gtataaggta ataggcacac 95040
tcactctaga ggaccaggat aaatggtatg aacttttgac atctatcaaa attctaagca 95100
gtccctttac ctcagcaatt tctcatctag caacctaagt gaaaacactc actcaacact 95160
caagatcgat gcagagggct ggctagggca gcacgggttg tattatcaaa aaccggaaac 95220
cccaaagtcc atcaacagga aactggttaa ataaattata atgaaggtta ggcacagtgg 95280
ctcacacctg taatcccagc actttgggag ggcaaggtgg aaggactgct tgaagccagg 95340
aattcaagac cagtcagggc agcaaagcaa gaccccatct ctatttttaa aaaactatgt 95400
aactggctgg gtgtggtggc tctactaaaa atacaataat taggtgggta tggtggcatg 95460
cgcctgtaat cccagctact cgggaggctg aggcaggaga atcacttgaa cccaaaaggt 95520
ggaggttgca gtgagagcag ataacgccac tgcactccag cctgggtgac agagcgagac 95580
tccgtctcaa aataataata ataataataa taataataat aataataata ataaggcagg 95640
tatgtatttg gggctcctgc taaatgagat tttagcttct cttgccacac acaaaatttg 95700
taactgtgag ataacagatg tcaatctgct tcattacagt taccatttta ctatctgtat 95760
gtatgctatg ttatatatca taaacataca taagaatatt ttttaagaaa gaataggacc 95820
ggtcgcagtg gctcatgcct gtaatcccag cactttggga ggccaaggtg ggcagatcgc 95880
gaggtcagga gatcgagacc atcctagcca acacagtgaa accatatctc tactaaaaat 95940
acaaaaatta gccgggtgtg gtggggcgcc cctgtagtcc cagctactca ggaggctgag 96000
gcaggagaat tgcttgaacc cgggaggcag aggttgcagt gagacgagat tgcaccactg 96060
tactccagcc tggcaacaga gcaagattct gtctcaaaac aaacaaacga aaaaagaata 96120
gccaggtgcg gtggctcaca cctgtaatct caacacttcg ggaggctgag gtgggcagat 96180
cacctgaagt taggagtttg agaccagcct ggccaacatg gtgaaacccc gtctccacta 96240
aactacaaaa attagccaag catggtggcc catgcctgtt gtcccagcta ctccggaggc 96300
tgaggcccaa gaatcacttg aaccttggga ggcggaggtt gcagtgagcc aaattcacgc 96360
actgcactcc agcctgggca acaaagctag actctctcaa aaataaataa ataaataaat 96420
aaataaataa ataaataaat aaataaggca gctctacatg catgaataga aacaagttgc 96480
aacaaagtat gtattgtgac tcccctttgt tctttttcct ttgagacagg gtcttgctct 96540
atcgcccaag ctggagtgcg gtggcatggt cttggctcac tgcaacctcc acctcccaag 96600
cttaagccat cctcccacct cagtctccag tgtagctgga actatgggtc ctcgttaggg 96660
ttattttgtt tggttggttg gtttttattg agacagagtc tcactctgtc acccaggttg 96720
gcgtgcagtg gctcaatctt ggctcactgc aacctacacc tcctgggttc aagcaattct 96780
cgcgcctcag cctcctgagt agctggaatt acaggtgtat gccgccacca tgcccggcta 96840
atttagtaga aatgggtttt tgccatgttg accagactgg tctcaaactc ctgacctcaa 96900
gtaatcctcc cacctcggcc taacaaagtg ttgggactac aggcgtaagc caccgtgcgt 96960
ggccctcatt agggttttgg gactagagct acaaagccac tgaagtaagg tggcatgaca 97020
ctggctttct agagtgcttc acacatttct gtaatgtttt aatttagtaa tagtcatatg 97080
atgtttccct aatgagaaca aaacagacat tgtactccct atacacggct ggaagcataa 97140
gtaaatccag cctttgaaaa ttcatatcaa ggctgggcat ggtgacatgc acttgtaatc 97200
ccagctattc aggaagctga ggaaggaaga tcccttgagc ccaggagttt gagaccagcc 97260
taagcaacat agtaagaccc cgtctcaaaa acaaaacaaa acaaatttca catcaaaaga 97320
ttaactgtaa caaaaagaaa ttgtaacaaa ataaatacat attaaacata tgaaaccctt 97380
tgcacttaga tcagaaagtg tgactaacac attatgttgg tgagggtatg atgtatatgt 97440
aagatactct tacacattga cagggaaatg taaagagaaa ccctcattct gaggggcaat 97500
ttagcaacat ggatcaatat gaaaaacaca catcccttac ccaacaattt tacttccagg 97560
aacttacttg accaccaacc tcactgttaa caaacaagtc tgccctcaag acacataata 97620
tttgcagaat tctgtggaca gaggatttag tacacactgc tttcatcctg tgattgccct 97680
aagtactttc agaaatgtaa acagtcctga cacatgtggt ctttgaatat ggtcaaacac 97740
ctcattcttc agctttggta tctcataaca aattgttgca taaagtatga aaaatacata 97800
ttggtgatac tatttattta tttagtctct tcttgcaaag agaagaaata aacaaaagga 97860
gaaaggctca tgtctggaat cccagcaatt taggaggctg aggagggagg actgctagag 97920
cccaggagtt tgagaccagc ctgggcaatg tgacaagact ctgtctctat aaaaaaggag 97980
aaagtgaata gtgtcttgtc tcaaaaaaaa aaaaaaaaaa aaaaaaaaga agaaagtgag 98040
tagaaagaga gctttttgga tatctaaata aaagctgaca gggccaggca cagtggctca 98100
cgcctgtaat cccagcactt tgggaggcca aggcgggggg atcacttgag gtcaggagtt 98160
cgagaccagc ctggccaata tggcaaaacc ccatctctac taaaaataca aaaattagcc 98220
gggcgtggtg cctgcaatgc cagctactcg ggaggctgag gtaggagaac tgcttgaacc 98280
tgggaggcgg aggctgcagt gagccgagtt tgtgccgctg cactccagcc tgggcaacaa 98340
gagtgaaact ctgtctcaaa gaaaaaaaaa aaaaattagc caggtgtggt ggtgcatgcc 98400
tgtaatccca gctactcagg aggctgaggc aggagaatcg cttgaacatg ggaggcggag 98460
gttgcagtga gccaagattg cgccactaca ctcagcctgg acaacagagc cagactccat 98520
ctgaaaaaaa aaaacaaaac accaaaaatt agccgagtgt ggtggagcat gcttgtagtc 98580
acagctactc gggatgctga agtaggagga tggcttgagc ccctgggagg cagaggttgc 98640
attgagccaa gattgcacca ctgtactcca gcctgggcaa cagagccaga ccttgtctca 98700
taaaattaac taattcatta attaaaactg ctcaaacctt gggtgaggtg tggcttctta 98760
caagaccaaa agcgtcaaaa aaaaaatagt acaatgttgg ggccaggtgg ttcacacctg 98820
taatcccagt actctgggaa gctgaagcag gactgcttga ggctaaaggt tcaaggtcag 98880
cctgggtaac atagtaagac cccaactcta caaaaaatac caaaaaaatt agctgggtgt 98940
ggtggtacaa cttgcagttg tacctactgg ggatgttgag gcaaaaagat cacttgagac 99000
caggagttta aggctacagt gagctacaat cacaccactg cactccaggt tgggcaacaa 99060
agcaagaacc ctgcttcact gataagaata agaaggcgga gaagaagaag aaattggact 99120
acatcaacat gaaaagcttt tgtactgaaa atgataccac caataaaatt aaaagccata 99180
gaaattagaa aaaatatttg caaatcatat atttaataag ggacttatat gcagtatata 99240
taaagaacac aacttggctg gatgcagtgg ctcacgcctg taatcctagc actttgggag 99300
gctgaggtgg gcgtatcaca aggtcaggag tttgagacca gcctggccag catagtgaaa 99360
ccccgtctct actaaatata ccaaaaaaaa aaaaaaaaaa aaattagcta ggcgtggcgg 99420
tgtgcgcctg tagtcccagc tactcgggag gctgaggcag gagaatcgct tgaacctggg 99480
aggcggaggt tacagtgagc cgagatggca tcactgcact ccagcctggg tgacagagtg 99540
agactccgtc tgaaaaaaaa aaacaaaaca aaaacaagac caaaaaaaga tcacaactca 99600
ataacaaaag gcaactcaat ttaaaagcac gcaaaggatt taaacagaca tttctcaaaa 99660
aagatatatg aatggccaat aagtacacaa aaagatgttt aacgtgatta gtcatcaatg 99720
aaacacaaat caaaacataa gacaccactt cgcacccact aggatggcta aaagaaaaaa 99780
ggcagtaaca agtataggga catagagcaa ttggaatcct catatactgc ttgtgaatat 99840
gtaaaatagc gcagccactc tggaaagtaa cctgacaatt cctcaaaata ttaaacacag 99900
acatggtggt tcgtgcctac agtcccagct accagggaag ctggggcagg agtattgatt 99960
gagcccagga gttcaaggac agcctacaca acatagcaag accctcatct taaaaaaaaa 100020
aaaaaaaaaa aagccaaaaa aaggccatga acagtttcat tcatgcaatc caagcatttc 100080
agggggccaa ggcaggagga tcacttgaag caaggagttc aagaccagct tgggcaccaa 100140
agtgggactc catttccaca aatttttttt tttttttgga gacggagtct cgttctgtca 100200
cccaggctgg agtgcagtgg cgtatctcag ctcactgcaa gctctgcctc ccgggttcgt 100260
gccattctcc tgcctttgcc tcccgggttt atgccattct cctgccccag cctcccgagt 100320
agctgggact acaggcatcc gccaccatgc ccggctaatt ttttgtattt ttagtagaga 100380
cggagtttca ccacgttagc caggatggtc tcgatctcct gacctcgtga tccgccagcc 100440
ttggcctccc acagtgctga ggttacaggc gtgagccacc acgcccagca aaaaaatttt 100500
gtttaattag cctcgtgttg tggcatgtgc ctgtagtggc aggaggctga ggcgggagga 100560
ttgcttgagc ccaggagttc aaggctgcag tgagccatga ttgcactgca atacagtctg 100620
tgttacagag tgagacctca ttaaaaataa ataaataaat aaaagttaaa agagctgggt 100680
gcggtggctc aagcctgtaa tcccagcact ttgggaggcc gaggtaggtg gatcacctga 100740
ggtcaggagt tcaagaccag cctggccaac ttggcgaaac ccagtctcta ctaaaaaata 100800
caaaaaatta gccgggtgtg gtggtgggcg tctgtaatcc cagtgactca gaggctgagg 100860
cacaagaatc gcttgaacct aggaggcaga ggttgcagtg agccgagatg gcgccactgc 100920
actccagcct gggcaacaca gagagactcc gtctcaaaaa aaaaataata ataataataa 100980
aaagttaaaa gttaccacac aacccaacaa tcccacttct tgctctataa ccaagagaaa 101040
taaaaataaa tgcccacaca aaaactacta cactaatgtt catagcaaca ttataatagc 101100
caaaaagtag aaatgaccca aatgtctatc agcagatgaa tgcaaattaa aaatgtggta 101160
gatacagaga tatgatggca tattattgat caataaaagg aaaagaggca acgagcacat 101220
gaaaagacgc tgaactcatt agtcactagg aaaatgcaaa tcaaaactac aaagatgcat 101280
cacttcacac ccaagtagga gggcctaacc agaaaaacag aaaatagtac ctgtttatga 101340
ggatgatgaa gcatttgaac cctcatacat cactggtggg aatgtaaatc ggtacaacca 101400
ctgtggaagt ttcgcggttc ggttaagtta aacacagaat tgactgtgta tgacccagta 101460
attccactcc caggtaaaga actgaaatca gatgttcaga ccaaaacttg tatgcaaatg 101520
ttcagagaag tactactcaa aataagcaaa aggtggaaat aatcaaaatg tccctcaact 101580
gatgaataga tatataaaat gtggtattat ccataaaatg gaatactact cagccgtaag 101640
gaataaagta gtgacacatg cgcagcaggg ataacccttg gaaacattac gttaagtgaa 101700
accagacaca aatggccacg tactgtataa ttccattgct atgaaatatt aatagagaaa 101760
tccagagaca gaaagtagat tagcagttgc caggggctgg gcgagggggg aaaatgggaa 101820
gtgactaaca gatgctcagt ttccttttag gataatgaaa agttctggaa ccagacagtg 101880
gtgatggttg tacaacacta taaaggtact gaaacccacc gaattgtgca ctttaaaatg 101940
gtaaacactg tcatatgtat ttcccaggta tttttttaat gaaatgaagt gctgaaacat 102000
gctacaacat ggatgaccct taaatacata agtaaaggaa atcagtcaca aaagtccacg 102060
tattttagga ttccatttat atgaaatgtc cagaataggg aaatttagag gcggaacata 102120
cagggcatac agagccaaga taagataatt tttttttttt tttttttttt gagactgagt 102180
ctcgccctgt tgcccaagct ggagtgcagt ggcgtgatct cggctcaccg caacctccac 102240
ctcccgggtt ccagggttct cctgcctcag ccaccccagt agctgggatt acaggcgccc 102300
gccaccaccc ccggctaatt tttgtatttt tagtagagac ggggtttcac catgctggcc 102360
aggctggtct cgaactcctg acctcgtgat ccgcccatct cggcctccca aagtgctggg 102420
attacaggca tgagccaccg cacccggcct attctttttt cttttaaaat ttttatttta 102480
aaaatttatt tttttaaatt tatccagcgt ctcacgacgc tgtctcgaaa aaaaaaaaag 102540
tatcggcctg gcgggcggtg gctcacgcct gtaatgccag cactttggga ggccaaggcg 102600
gtcaaattat ctgaggtcag gagttcgaga ccagcctgac caacatggag aaaccctgtc 102660
tctactaaaa atacaaaaaa taaaaataat aaaaaaaaat tagccgggca tgatggtgca 102720
tgcctgtaat cccagctatt caggaggctg aggcaggaga atcgcttgaa ccaaggaggc 102780
agaggttgca gtgagccgag atcacgccat tgcactctag cctgggcaat aagagcgaaa 102840
caccgtctca ataaataaat aaatatcaga aattggccca gcatggtggc tcacgcctgt 102900
aatcccagaa gaggtgggca gatcgcttga gcccagagct cgagaccagc ctggccaaca 102960
tggcgaaaac ccgtctccac taaaaataca aaactgagtc gggcgtggtg gcccgtgcct 103020
ctaatcccag ctactccgga ggccgaggtg ggaggatcgc ttgagcctgg gaaacggagg 103080
ttgcagtgag ccgagctcgt gacactgcac tccagcctgt gtgacagagt gagaccctgt 103140
ctcaaaaacc accagaacta ttagtagttt acattatttg gttagtctgg aaactaatta 103200
cgttgagaaa ctgactgaag cttgattatt tctattatac acagacttca aacattccag 103260
aacttactgt taaagtcaga tttaccctcc ttgtgagaca gacgcccaga gcttggactt 103320
attcgtttgc tttatagaaa ctccctaact tatttcactt ctcatactag actttaagct 103380
ccaaagccag agaccatgac ttccattcct tccggatccc ccagcggaat gtaaaaactc 103440
cagaaagcat ttcctaaatg cctgccgaaa gacggctact gagcatgccc ggcttggcca 103500
agtcaatttc aacaacattc tgaaacaaaa actatagttc ccgcgttaca aggtggaaaa 103560
aagggaataa acgggagcaa agcctaagga ttcaatctat atgagggggt taaggaaagg 103620
taaagttcaa gggcggcgca gacgtgaagg acagcactat cacagcttaa acttggtact 103680
cggtaaactg gtgtcgaacc agaacgacca aagaaaggct taaaaaaaat actagattaa 103740
cgagtgaggg aaggccaacg ggggtgcagg gtatcgatga cgtaggctga ccacagtttt 103800
ttctaaagct gccctctaca aaaataatac taagatgatc aggccttcgg tgtcaacacc 103860
aacaagatac actgtgatga agctcacttc caaaaagttc ctttttacaa acgaaagagc 103920
cgtgctgtgg ccaagatacc ccaaccatca acgcttgcta agctctcagc tcctgccttc 103980
atctccaccg ccatcttctg gatgggaacc caaaccttcc taaagtgctt tggccagcat 104040
cacctccgcg cacagcccgg gaagcctgcg tttcccaggt cgcgcagacg gcgcaaaggg 104100
ggaaactcca cctcgctcgg ctccgcgcct cccaaatgca cgcaaagggc tgccgtcttc 104160
ctttccccta ccccgcccgg gctttccaag gtccggcgcg aggagcccgc gaggcgcggt 104220
gcgcgggcct cacctgcaca cgccgcgaat gcagggctcc agccagatgc ggtaagcggt 104280
ctcgatgtgc tcctgcgaca cctcctcggg ccgcaccgtc tccgcccagc gccaggccgc 104340
cttctccagc tgcagccgcg gggccatggc cttggcccca ggaacgcctc ccgagccaga 104400
ccgccgcagc cgccgccgcg gtctgcaccg ccgccccaat gggcttcgcc acctgccagc 104460
aaggaggacc tggcgctcct tcaggcagct ggccagtcaa tcacctgtgc gcgccactgc 104520
cgccgcgccc gcccgcgccc gacccgcacg accggccgca aagcgccgcc gtcgacaccc 104580
gacacacccc gcgcccgcgg acgtt 104605
<210> 2
<211> 1035
<212> PRT
<213> human
<400> 2
Met Ala Pro Arg Leu Gln Leu Glu Lys Ala Ala Trp Arg Trp Ala Glu
1 5 10 15
Thr Val Arg Pro Glu Glu Val Ser Gln Glu His Ile Glu Thr Ala Tyr
20 25 30
Arg Ile Trp Leu Glu Pro Cys Ile Arg Gly Val Cys Arg Arg Asn Cys
35 40 45
Lys Gly Asn Pro Asn Cys Leu Val Gly Ile Gly Glu His Ile Trp Leu
50 55 60
Gly Glu Ile Asp Glu Asn Ser Phe His Asn Ile Asp Asp Pro Asn Cys
65 70 75 80
Glu Arg Arg Lys Lys Asn Ser Phe Val Gly Leu Thr Asn Leu Gly Ala
85 90 95
Thr Cys Tyr Val Asn Thr Phe Leu Gln Val Trp Phe Leu Asn Leu Glu
100 105 110
Leu Arg Gln Ala Leu Tyr Leu Cys Pro Ser Thr Cys Ser Asp Tyr Met
115 120 125
Leu Gly Asp Gly Ile Gln Glu Glu Lys Asp Tyr Glu Pro Gln Thr Ile
130 135 140
Cys Glu His Leu Gln Tyr Leu Phe Ala Leu Leu Gln Asn Ser Asn Arg
145 150 155 160
Arg Tyr Ile Asp Pro Ser Gly Phe Val Lys Ala Leu Gly Leu Asp Thr
165 170 175
Gly Gln Gln Gln Asp Ala Gln Glu Phe Ser Lys Leu Phe Met Ser Leu
180 185 190
Leu Glu Asp Thr Leu Ser Lys Gln Lys Asn Pro Asp Val Arg Asn Ile
195 200 205
Val Gln Gln Gln Phe Cys Gly Glu Tyr Ala Tyr Val Thr Val Cys Asn
210 215 220
Gln Cys Gly Arg Glu Ser Lys Leu Leu Ser Lys Phe Tyr Glu Leu Glu
225 230 235 240
Leu Asn Ile Gln Gly His Lys Gln Leu Thr Asp Cys Ile Ser Glu Phe
245 250 255
Leu Lys Glu Glu Lys Leu Glu Gly Asp Asn Arg Tyr Phe Cys Glu Asn
260 265 270
Cys Gln Ser Lys Gln Asn Ala Thr Arg Lys Ile Arg Leu Leu Ser Leu
275 280 285
Pro Cys Thr Leu Asn Leu Gln Leu Met Arg Phe Val Phe Asp Arg Gln
290 295 300
Thr Gly His Lys Lys Lys Leu Asn Thr Tyr Ile Gly Phe Ser Glu Ile
305 310 315 320
Leu Asp Met Glu Pro Tyr Val Glu His Lys Gly Gly Ser Tyr Val Tyr
325 330 335
Glu Leu Ser Ala Val Leu Ile His Arg Gly Val Ser Ala Tyr Ser Gly
340 345 350
His Tyr Ile Ala His Val Lys Asp Pro Gln Ser Gly Glu Trp Tyr Lys
355 360 365
Phe Asn Asp Glu Asp Ile Glu Lys Met Glu Gly Lys Lys Leu Gln Leu
370 375 380
Gly Ile Glu Glu Asp Leu Ala Glu Pro Ser Lys Ser Gln Thr Arg Lys
385 390 395 400
Pro Lys Cys Gly Lys Gly Thr His Cys Ser Arg Asn Ala Tyr Met Leu
405 410 415
Val Tyr Arg Leu Gln Thr Gln Glu Lys Pro Asn Thr Thr Val Gln Val
420 425 430
Pro Ala Phe Leu Gln Glu Leu Val Asp Arg Asp Asn Ser Lys Phe Glu
435 440 445
Glu Trp Cys Ile Glu Met Ala Glu Met Arg Lys Gln Ser Val Asp Lys
450 455 460
Gly Lys Ala Lys His Glu Glu Val Lys Glu Leu Tyr Gln Arg Leu Pro
465 470 475 480
Ala Gly Ala Glu Pro Tyr Glu Phe Val Ser Leu Glu Trp Leu Gln Lys
485 490 495
Trp Leu Asp Glu Ser Thr Pro Thr Lys Pro Ile Asp Asn His Ala Cys
500 505 510
Leu Cys Ser His Asp Lys Leu His Pro Asp Lys Ile Ser Ile Met Lys
515 520 525
Arg Ile Ser Glu Tyr Ala Ala Asp Ile Phe Tyr Ser Arg Tyr Gly Gly
530 535 540
Gly Pro Arg Leu Thr Val Lys Ala Leu Cys Lys Glu Cys Val Val Glu
545 550 555 560
Arg Cys Arg Ile Leu Arg Leu Lys Asn Gln Leu Asn Glu Asp Tyr Lys
565 570 575
Thr Val Asn Asn Leu Leu Lys Ala Ala Val Lys Gly Ser Asp Gly Phe
580 585 590
Trp Val Gly Lys Ser Ser Leu Arg Ser Trp Arg Gln Leu Ala Leu Glu
595 600 605
Gln Leu Asp Glu Gln Asp Gly Asp Ala Glu Gln Ser Asn Gly Lys Met
610 615 620
Asn Gly Ser Thr Leu Asn Lys Asp Glu Ser Lys Glu Glu Arg Lys Glu
625 630 635 640
Glu Glu Glu Leu Asn Phe Asn Glu Asp Ile Leu Cys Pro His Gly Glu
645 650 655
Leu Cys Ile Ser Glu Asn Glu Arg Arg Leu Val Ser Lys Glu Ala Trp
660 665 670
Ser Lys Leu Gln Gln Tyr Phe Pro Lys Ala Pro Glu Phe Pro Ser Tyr
675 680 685
Lys Glu Cys Cys Ser Gln Cys Lys Ile Leu Glu Arg Glu Gly Glu Glu
690 695 700
Asn Glu Ala Leu His Lys Met Ile Ala Asn Glu Gln Lys Thr Ser Leu
705 710 715 720
Pro Asn Leu Phe Gln Asp Lys Asn Arg Pro Cys Leu Ser Asn Trp Pro
725 730 735
Glu Asp Thr Asp Val Leu Tyr Ile Val Ser Gln Phe Phe Val Glu Glu
740 745 750
Trp Arg Lys Phe Val Arg Lys Pro Thr Arg Cys Ser Pro Val Ser Ser
755 760 765
Val Gly Asn Ser Ala Leu Leu Cys Pro His Gly Gly Leu Met Phe Thr
770 775 780
Phe Ala Ser Met Thr Lys Glu Asp Ser Lys Leu Ile Ala Leu Ile Trp
785 790 795 800
Pro Ser Glu Trp Gln Met Ile Gln Lys Leu Phe Val Val Asp His Val
805 810 815
Ile Lys Ile Thr Arg Ile Glu Val Gly Asp Val Asn Pro Ser Glu Thr
820 825 830
Gln Tyr Ile Ser Glu Pro Lys Leu Cys Pro Glu Cys Arg Glu Gly Leu
835 840 845
Leu Cys Gln Gln Gln Arg Asp Leu Arg Glu Tyr Thr Gln Ala Thr Ile
850 855 860
Tyr Val His Lys Val Val Asp Asn Lys Lys Val Met Lys Asp Ser Ala
865 870 875 880
Pro Glu Leu Asn Val Ser Ser Ser Glu Thr Glu Glu Asp Lys Glu Glu
885 890 895
Ala Asn Pro Asp Gly Glu Lys Asp Pro Asp Phe Asn Gln Ser Asn Gly
900 905 910
Gly Thr Lys Arg Gln Lys Ile Ser His Gln Asn Tyr Ile Ala Tyr Gln
915 920 925
Lys Gln Val Ile Arg Arg Ser Met Arg His Arg Lys Val Arg Gly Glu
930 935 940
Lys Ala Leu Leu Val Ser Ala Asn Gln Thr Leu Lys Glu Leu Lys Ile
945 950 955 960
Gln Ile Met His Ala Phe Ser Val Ala Pro Phe Asp Gln Asn Leu Ser
965 970 975
Ile Asp Gly Lys Ile Leu Ser Asp Asp Cys Ala Thr Leu Gly Thr Leu
980 985 990
Gly Val Ile Pro Glu Ser Val Ile Leu Leu Lys Ala Asp Glu Pro Ile
995 1000 1005
Ala Asp Tyr Ala Ala Met Asp Asp Val Met Gln Val Cys Met Pro
1010 1015 1020
Glu Glu Gly Phe Lys Gly Thr Gly Leu Leu Gly His
1025 1030 1035
<210> 3
<211> 21
<212> DNA
<213> Artificial sequence
<400> 3
tgcctgctat aatcctggaa a 21
<210> 4
<211> 23
<212> DNA
<213> Artificial sequence
<400> 4
tcagcagaac cttctaagtc tca 23
<210> 5
<211> 23
<212> DNA
<213> Artificial sequence
<400> 5
ctggaaaact gctttacctg gaa 23
<210> 6
<211> 23
<212> DNA
<213> Artificial sequence
<400> 6
agccccgcta aagaataaac aaa 23
<210> 7
<211> 24
<212> DNA
<213> Artificial sequence
<400> 7
tgcctgctat aatcctggaa aact 24
<210> 8
<211> 24
<212> DNA
<213> Artificial sequence
<400> 8
ctcagcagaa ccttctaagt ctca 24
<210> 9
<211> 22
<212> DNA
<213> Artificial sequence
<400> 9
cattctaaaa catttgcctg ct 22
<210> 10
<211> 20
<212> DNA
<213> Artificial sequence
<400> 10
gccccgctaa agaataaaca 20
Claims (4)
1.USP48Application of detection reagent of gene mutation site in preparation of kit for assisting detection of pituitary adenoma or susceptibility thereof, wherein the pituitary adenoma is adrenocorticotropic hormone (ACTH) type pituitary adenoma, and the pituitary adenoma is of adrenocorticotropic hormone (ACTH) typeUSP48The gene mutation sites of the gene are as follows:
c → A at position 51169 or C → T at position 51169, and
position 51171T → C;
51174 position A → G;
51182 position C → T;
51198 position C → T;
51206 position C → T;
51207 position A → T, and
t → C at position 51239;
wherein the nucleotide position numbering is based on SEQ ID NO 1.
2. The use of claim 1, wherein the reagent comprises a primer, a probe or a chip.
3. The use according to claim 2, wherein the kit comprises one or more reagents selected from the group consisting of:
(a) To is directed atUSP48Specific primers for the gene;
(b) A specific probe for detecting the gene mutation site;
(c) A chip for detecting the gene mutation site.
4. The use of claim 1, wherein the agent comprises a primer pair selected from the group consisting of:
and (3) primer pair 2:
F: CTGGAAAACTGCTTTACCTGGAA (SEQ ID NO.5)
R: AGCCCCGCTAAAGAATAAACAAA (SEQ ID NO.6)；
and (3) primer pair 4:
F: CATTCTAAAACATTTGCCTGCT (SEQ ID NO.9)
R: GCCCCGCTAAAGAATAAACA (SEQ ID NO.10)。
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| CN113604561B (en) * | 2020-05-05 | 2024-02-06 | 北京市神经外科研究所 | Application of SF3B1 gene mutation in auxiliary diagnosis of hybrid PRL positive pituitary adenoma |
| CN113604562B (en) * | 2020-05-05 | 2024-01-02 | 北京市神经外科研究所 | Application of SF3B1 gene mutation in auxiliary diagnosis of prolactin type pituitary adenoma |
| WO2023159218A2 (en) * | 2022-02-18 | 2023-08-24 | Arizona Board Of Regents Of The University Of Arizona, A Body Corporate | Human pituitary neuroendocrine tumor organoids and methods of making and using the same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104593490A (en) * | 2014-12-23 | 2015-05-06 | 复旦大学附属华山医院 | Application of USP8 gene detection object in preparation for ACTH-type pituitary adenoma molecular pathological diagnosis and typing products |
| CN106434918A (en) * | 2016-09-26 | 2017-02-22 | 复旦大学附属华山医院 | Application of specific gene mutation in molecular diagnosis and targeted therapy of pituitary adenoma detection |
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| EP3019628A4 (en) * | 2013-07-12 | 2017-05-10 | The Regents Of The University Of Michigan | Recurrent gene fusions in cancer |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104593490A (en) * | 2014-12-23 | 2015-05-06 | 复旦大学附属华山医院 | Application of USP8 gene detection object in preparation for ACTH-type pituitary adenoma molecular pathological diagnosis and typing products |
| CN106434918A (en) * | 2016-09-26 | 2017-02-22 | 复旦大学附属华山医院 | Application of specific gene mutation in molecular diagnosis and targeted therapy of pituitary adenoma detection |
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