Recombination rate variation and evolution in primates

灵长类动物的重组率变化和进化

• 批准号: 7927966
• 负责人: MOLLY F PRZEWORSKI
• 金额: $ 38.05万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7927966
• 关键词: Address; American; Aneuploidy; Biology; Chromosomal Rearrangement; Chromosome Mapping; Chromosome abnormality; Chromosomes; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 22; Data; Developmental Disabilities; Embryo; Ensure; European; Event; Evolution; Female; Fertility; Founder Generation; Genetic; Genetic Recombination; Genome; Genomics; Genotype; Goals; Heritability; Homologous Gene; Human; Human Chromosomes; Human Genetics; Individual; Lead; Life; Linkage Disequilibrium; Location; Maps; Medical; Meiosis; Meiotic Recombination; Mind; Modeling; Molecular; Natural Selections; Ovum; Pan Genus; Pongidae; Population; Population Genetics; Predisposition; Primates; Process; Regulation; Relative (related person); Research; Research Design; Resolution; Role; Shapes; Single Nucleotide Polymorphism; Spontaneous abortion; Surveys; Testing; Time; Variant; Work; abstracting; base; comparative; design; genetic pedigree; genome-wide; human disease; human female; human male; hutterite; improved; insight; male; research study; sex; spatial temporal variation; sperm cell; tool; transmission process

Title: Recombination rate variation and evolution in primates Abstract: Errors in the meiotic recombination process underlie a variety of chromosomal abnormalities, which are associated with spontaneous miscarriages and a wide range of human diseases. In spite of the crucial importance of recombination in meiosis, recent studies have revealed tremendous variation in rates among human females, and a rapid evolution of fine-scale recombination rates in apes. These observations raise important questions about recombination rate variation within and between species and its determinants. Addressing these questions is a key medical challenge, as well as an important step in understanding how natural selection acts on recombination rates. Here, we propose a unique combination of experimental and computational approaches to: i) Quantify variation in recombination rates among human males and females, using dense genotyping data collected in a large pedigree of a founder population (the Hutterites). These data will be used to evaluate the reliability of linkage-disequilibrium based maps, and garner new insights into the genetic basis of recombination rate variation and its possible effects on fertility. ii) Characterize the evolution of broad-scale recombination rates by building a genome-wide genetic map for common chimpanzees, the closest living evolutionary relative of humans. By comparing the map to what is seen in humans, we can assess the evolutionary constraints acting on recombination over different genetic scales, and ask whether the same determinants of recombination are at work in the two species. iii) Test hypotheses about the evolution of recombination hotspots, and delimit the rate at which they evolve, by performing sperm-typing experiments in two human populations and in common chimpanzees. In summary, we propose to combine molecular and population genetics tools to address outstanding questions about selective constraints on human recombination, with important implications for human genetics and evolutionary biology. Project Summary: A substantial fraction of human embryos are aneuploid (i.e., have an abnormal number of chromosomes) and, as a result, do not survive to full term or have severe developmental disabilities. Most cases of aneuploidy are caused by errors in the meiotic recombination process. This work aims to characterize variation in the human recombination process and to understand its determinants, thereby improving our understanding of the susceptibility to aneuploidy.

标题：灵长类动物的重组率变异和进化 摘要：减数分裂重组过程中的错误是多种染色体异常的基础。 异常，与自然流产和多种 人类疾病。尽管重组在减数分裂中至关重要，但最近 研究表明，人类女性的发病率存在巨大差异，并且快速增长 猿中精细重组率的进化。这些观察结果提出了重要的 关于物种及其之间的重组率变化的问题 决定因素。解决这些问题是一个关键的医学挑战，也是一个 理解自然选择如何影响重组率的重要一步。 在这里，我们提出了实验和计算方法的独特组合 i) 量化人类男性和女性重组率的变化，使用 在创始人群体的大谱系中收集的密集基因分型数据（ 哈特派）。这些数据将用于评估连锁不平衡的可靠性 基于图谱，并对重组率的遗传基础获得新的见解 变异及其对生育能力的可能影响。 ii) 表征大规模的演化 通过为普通黑猩猩构建全基因组遗传图谱来提高重组率， 与人类最接近的现存进化亲属。通过将地图与所看到的进行比较 在人类中，我们可以评估对重组的进化限制 不同的遗传尺度，并询问是否存在相同的重组决定因素 在两个物种中工作。 iii) 检验重组演化的假设 热点，并通过执行精子分型来限制它们的进化速度 在两个人群和普通黑猩猩中进行的实验。综上所述，我们 建议结合分子和群体遗传学工具来解决突出问题 关于人类重组的选择性限制的问题，具有重要意义 对人类遗传学和进化生物学的影响。项目摘要：人类胚胎的很大一部分是非整倍体（即具有 染色体数量异常），因此无法存活至足月或已死亡 严重的发育障碍。大多数非整倍体病例是由基因错误引起的 减数分裂重组过程。这项工作旨在表征人类的变异 重组过程并了解其决定因素，从而改善我们的 了解对非整倍体的易感性。