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Collaborative Cross: A system genetics approach to the study of male infertility

协作交叉：研究男性不育的系统遗传学方法

基本信息

批准号：
8460773
负责人：
Deborah A. O'Brien
金额：
$ 31.81万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8460773
关键词：
Address Alleles Animal Model Animals Assisted Reproductive Technology Biochemical Pathway Biological Process Cataloging Catalogs Characteristics Collaborations Complement Complex Computational Biology Computer Assisted Contraceptive methods Couples Data Defect Derivation procedure Development Dissection Epididymis Extinction (Psychology)Fertility Future Generations Genes Genetic Genetic Epistasis Genetic Structures Genomics Genotype Histology Human Inbred Mouse Inbreeding Incidence Infertility Knock-out Knockout Mice Lead Male Infertility Maps Medical Methods Molecular Mus Mutagenesis Mutation Phenotype Physiological Population Production Quantitative Trait Loci Recombinants Reporting Reproduction Reproductive Biology Research Research Proposals Resolution Resources Risk Scientist Seminal Vesicles Shapes Side Sperm Count Procedure Sperm Motility System Testis Time Validation Variant Weight Work base density design fitness gene function genetic variant interest male mouse model novel offspring public health relevance purge reproductive research study sperm analysis tool trait

项目摘要

DESCRIPTION (provided by applicant): The long-term objectives of this research are to understand the genetics of male infertility. The Collaborative Cross is a mammalian reference population that was designed to provide a cross-disciplinary platform for systems genetics in the most popular mammalian model organism, the mouse, and to overcome limitations of existing platforms. During the derivation of the Cross, approximately half of the lines are becoming extinct and male infertility is a major cause of lost lines. Characterization of males from the extinct lines provides a transient, but unique opportunity, for substantial genetic dissection of male infertility. We have assembled an expert group of scientists with complementary strengths in reproductive biology, genetics/genomics and computational biology and a strong record of productive collaborations to take full advantage of this window of opportunity. The surviving lines of the Collaborative Cross provide additional resources for validation and in-depth physiological and molecular analyses. Our specific aims are to: 1) complete the phenotypic characterization of males from extinct CC lines and genotype them with the high-density genotyping array; 2) identify loci associated with phenotypic variation for major male reproductive traits including abnormal testis histology, testis weight, sperm count, sperm motility and infertility; and 3) provide independent validation of the infertility loci mapped in the extinct funnels, conduct in-depth phenotypic analysis of males with genotypes associated with male infertility and identify the underlying molecular mechanisms leading to male infertility. )

描述（由申请人提供）：本研究的长期目标是了解男性不育的遗传学。协作交叉是一个哺乳动物参考群体，旨在为最流行的哺乳动物模式生物小鼠的系统遗传学提供跨学科平台，并克服现有平台的局限性。在十字架的衍生过程中，大约一半的品系正在灭绝，男性不育是丧失品系的主要原因。从灭绝线的男性特征提供了一个短暂的，但独特的机会，大量的遗传解剖男性不育。我们已经组建了一个科学家专家组，他们在生殖生物学、遗传学/基因组学和计算生物学方面具有互补优势，并在富有成效的合作方面有着良好的记录，以充分利用这一机会之窗。协作杂交的幸存品系为验证和深入的生理和分子分析提供了额外的资源。我们的具体目标是：1）完成来自灭绝CC系的雄性的表型表征，并用高密度基因分型阵列对其进行基因分型; 2）鉴定与主要雄性生殖性状的表型变异相关的基因座，所述主要雄性生殖性状包括异常睾丸组织学、睾丸重量、精子计数、精子活力和不育;和3）提供在灭绝漏斗中绘制的不育基因座的独立验证，对具有与男性不育相关基因型的男性进行深入的表型分析，并确定导致男性不育的潜在分子机制。)