Mutation Rate Variation Among Human Genomic Regions

人类基因组区域的突变率变异

基本信息

批准号：
6726902
负责人：
WEN-HSIUNG LI
金额：
$ 22.42万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-01 至 2005-04-30
项目状态：
已结题

项目摘要

Our goal is to understand variability in the rates and patterns of mutation among regions of the human genome and the causes of this variation. Specifically, we shall address the following issues: 1. How different are the mutation rates among homologous sequences on different types of chromosome (autosomes, X chromosome, and Y chromosome)? The aim is to estimate the magnitude of difference between male and female mutation rates. 2. How variable are the mutation rates among regions of a chromosome or chromosomes of the same type? 3. Does the pattern of mutation different among genomic regions? Issues 2 and 3 are the essence of the regional mutation pressure hypothesis, which postulates that the rate and pattern of mutation varies among regions of the mammalian genome. We shall test this hypothesis and study the origin and evolution of GC-rich isochores. 4. Is the variation in the level of single nucleotide polymorphism (SNO) among human genomic regions due in a large extent to variations in mutation rate. To study these issues, we propose to pursue the following work. 1. To search for pairs of non-coding regions that are homologous (very similar) between X and Y chromosomes, or between Y and an autosome, or between X and an autosome, and choose several (5 to 7) pairs of regions that are suitable for estimating sex differences in mutation rate. Each pair of regions will be sequenced in several higher primates (e.g.. chimpanzee, gorilla, orangutan, siamang, gibbon, and possibly Old World monkeys. 2. Select approximately 15 unique Y-linked DNA segments each of 2-5 kb in length, These segments should be non-coding, should have no homologue on any autosome or X chromosome, and should have a wide coverage of GC contents. Sequence each segment in several higher primates. 3. Similarly, select approximately 50 unique autosomal DNA segments each of approximately 5 kb in length. We will try to select segments that have SNP data and have suitable GC contents and recombination rates. Sequence each of them in chimpanzee, gorilla, orangutan, siamang, baboon and colobus. 4. To conduct statistical analyses of the new and existing data to address the above issues.

我们的目标是了解人类基因组区域之间突变率和模式的变异性以及这种变异的原因。具体来说，我们要解决以下问题： 1、不同类型染色体（常染色体、X染色体、Y染色体）上同源序列的突变率有多大差异？目的是估计男性和女性突变率之间的差异程度。 2. 一条或多条同类型染色体区域之间的突变率有多大？ 3. 基因组区域之间的突变模式是否不同？问题 2 和问题 3 是区域突变压力假说的本质，该假说假设哺乳动物基因组不同区域的突变率和模式有所不同。我们将检验这一假设并研究富含 GC 的等容线的起源和进化。 4. 人类基因组区域之间单核苷酸多态性（SNO）水平的差异在很大程度上是由于突变率的差异造成的。为研究这些问题，我们建议开展以下工作。 1. 搜索 X 和 Y 染色体之间，或 Y 和常染色体之间，或 X 和常染色体之间同源（非常相似）的非编码区对，并选择几对（5 到 7）个区域适用于估计突变率的性别差异。每对区域将在几种高等灵长类动物（例如黑猩猩、大猩猩、红毛猩猩、合趾猿、长臂猿，可能还有旧世界猴）中进行测序。 2. 选择大约 15 个独特的 Y 联 DNA 片段，每个片段长度为 2-5 kb，这些片段应该是非编码的，在任何常染色体或 X 染色体上都应该没有同源物，并且应该具有广泛的 GC 含量。 3. 同样，选择大约 50 个长度约为 5 kb 的常染色体 DNA 片段，我们将尝试选择具有合适 GC 含量和重组率的黑猩猩、大猩猩、猩猩的片段。、合趾猴、狒狒和疣猴 4. 对新数据和现有数据进行统计分析，以解决上述问题。