Genomic Studies Mammalian Y Chromosomes

描述（由申请人提供）：这个为期5年的项目的目标是（1）启动并完成5个物种-恒河猴，绒猴，大鼠，公牛和负鼠的Y染色体测序，以及（2）完成鸡W染色体的测序（目前约10%测序）。NHGRI已经批准了这五条Y染色体和鸡W染色体的靶向全规模测序。新的Y染色体将被添加到我们目前三个性染色体测序项目的队列中，即小鼠Y和鸡Z和W，它们处于不同的完成阶段。我们的目标是在下一个5年资助期结束前完成所有8条染色体的测序和注释。在过去的18年里，基因组研究表明，Y染色体在生物学上比任何人都更丰富，在医学上比任何人都更重要。这些基因组研究最近在人类和黑猩猩Y染色体的完成和注释序列中达到高潮，这是迄今为止唯一从任何物种，脊椎动物或无脊椎动物，植物或动物中测序的性别特异性染色体。人类Y染色体序列的知识使研究人员能够识别和表征复发性Y染色体缺失，这已成为男性不育症的最常见已知原因。黑猩猩的比较测序揭示了人类Y染色体上基因的功能重要性。我们怀疑NHGRI的六个高优先级测序目标-恒河猴，绒猴，大鼠，公牛，负鼠和鸡-的性别特异性染色体也将被证明具有巨大的生物医学意义。新Y染色体的序列将提供对人类Y染色体在健康和疾病中的作用的深入了解，并将为阐明哺乳动物和人类生殖细胞发育和精子生产提供必要的基础设施。鸡的W染色体将是第一个从任何物种中测序的雌性特异性染色体。我们预计W染色体的序列将通过提供对女性生育力，卵子发生和性别决定的见解来告知我们对人类生物学的理解。 公共卫生相关性：近几十年来，对人类、黑猩猩和小鼠的基因组研究表明，Y染色体在生物学上比任何人都更丰富，在医学上比任何人都更重要。五个新物种的Y染色体序列-恒河猴，绒猴，大鼠，公牛和负鼠-可能会被证明具有巨大的生物医学意义，为人类Y染色体在健康和疾病中的作用提供见解，并为阐明哺乳动物和人类生殖细胞发育和精子生产提供必要的基础设施。鸡的W染色体，作为哺乳动物Y染色体的女性对应物，将通过提供对女性生育力，卵子发生和性别决定的见解来告知我们对人类生物学的理解。

DESCRIPTION (provided by applicant): The aims of this 5-year project are to (1) initiate and complete the sequencing of the Y chromosomes of five species - rhesus macaque, marmoset, rat, bull, and opossum, and (2) complete the sequencing of the chicken W chromosome (currently ~10% sequenced). NHGRI has approved the targeting of these five Y chromosomes and the chicken W chromosome for full-scale sequencing. The new Y chromosomes will be added to our queue of three current sex chromosome sequencing projects, the mouse Y and the chicken Z and W, which are in various stages of completion. Our goal is to complete the sequence and annotation of all 8 chromosomes by the end of the next 5-year funding period. During the last 18 years, genomic studies have revealed that Y chromosomes are biologically richer and medically more important than anyone would have predicted. These genomic studies recently culminated in the finished and annotated sequences of the human and chimpanzee Y chromosomes, which are, to date, the only sex-specific chromosomes to have been sequenced from any species, vertebrate or invertebrate, plant or animal. Knowledge of the human Y chromosome sequence has allowed researchers to identify and characterize recurrent Y deletions, which have emerged as the most common of the known causes of infertility in men. Comparative sequencing in chimpanzee has shed light on the functional importance of genes on the human Y chromosome. We suspect that the sex-specific chromosomes of six of NHGRI's high-priority sequencing targets - rhesus, marmoset, rat, bull, opossum, and chicken - will also prove to be of great biomedical interest. The sequences of the new Y chromosomes will offer insight into the human Y chromosome's role in health and disease and will provide essential infrastructure for elucidating mammalian and human germ cell development and sperm production. The chicken W chromosome will be the first female-specific chromosome to be sequenced from any species. We anticipate that the sequence of the W chromosome will inform our understanding of human biology by offering insights into female fertility, oogenesis, and sex determination. PUBLIC HEALTH RELEVANCE: In recent decades, genomic studies in human, chimpanzee, and mouse have revealed that Y chromosomes are biologically richer and medically more important than anyone would have predicted. The Y chromosome sequences of five new species - rhesus macaque, marmoset, rat, bull, and opossum - will likely prove to be of great biomedical interest as well, offering insights into the human Y chromosome's role in health and disease and providing the essential infrastructure for elucidating mammalian and human germ cell development and sperm production. The chicken W chromosome, as the female counterpart of the mammalian Y, will inform our understanding of human biology by offering insights into female fertility, oogenesis, and sex determination.