Recombination rate variation and evolution in primates

标题：灵长类动物的呼吸速率变化和进化 翻译后摘要：减数分裂重组过程中的错误是各种染色体的基础。 异常，这与自发性流产和广泛的 人类疾病。尽管重组在减数分裂中至关重要， 研究表明，人类女性之间的比率存在巨大差异， 猿类精细重组率的演变。这些意见提出了重要的 关于种内和种间重组率变化及其 决定因素解决这些问题是一个关键的医学挑战，以及 理解自然选择如何影响重组率的重要一步。 在这里，我们提出了一个独特的实验和计算方法相结合 i）使用以下方法量化人类男性和女性之间重组率的变化： 密集的基因分型数据收集在一个大谱系的创始人人口（ Hutterites）。这些数据将被用来评估连锁不平衡的可靠性 的地图，并获得新的见解重组率的遗传基础 变异及其对生育力的可能影响。（二）大规模的发展 通过为普通黑猩猩构建全基因组遗传图谱， 与人类进化关系最近的现存物种通过将地图与所看到的 在人类中，我们可以评估作用于重组的进化限制， 不同的遗传尺度，并询问是否相同的决定因素重组是在 在两个物种中工作。iii）测试关于重组进化的假设 热点，并界定它们进化的速度，通过执行精子分型 在两个人类群体和普通黑猩猩身上进行的实验。总之，我们 建议将分子和群体遗传学工具联合收割机结合起来， 关于人类重组的选择性限制的问题， 对人类遗传学和进化生物学的影响。项目概述：相当一部分人类胚胎是非整倍体（即，有 染色体数目异常），因此不能存活至足月或 严重的发育障碍。大多数非整倍体的病例是由染色体上的错误引起的。 减数分裂重组过程这项工作的目的是表征人类的变化， 重组过程，并了解其决定因素，从而提高我们的 对非整倍体易感性的理解。

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.