Evolution of Chromosome-specific Low Copy Repeats

染色体特异性低拷贝重复的进化

• 批准号: 6423004
• 负责人: TAMIM H SHAIKH
• 金额: $ 24.99万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6423004
• 关键词: Pan; animal genetic material tag; baboons; biochemical evolution; chromosome aberrations; chromosomes; comparative genomic hybridization; fluorescent in situ hybridization; gene duplication; gene rearrangement; genetic disorder; genetic polymorphism; human genetic material tag; polymerase chain reaction; population genetics; restriction mapping; southern blotting

DESCRIPTION (provided by applicant): Large scale duplication of genetic material is a major force driving the evolution of genetic diversity. Gene duplication and subsequent divergence have been instrumental in the creation of new genes with specialized functional roles, a process that has been important for the creation of evolutionary diversity and speciation. The accumulating sequence of the human genome has revealed a class of genomic duplications that are chromosome-specific. Interestingly, these chromosome-specific sequence duplications or low copy repeats (LCRs) have been implicated in a number of human genetic disorders that are associated with recurrent genomic rearrangements. It has been proposed that illegitimate recombination facilitated by the highly homologous duplicated sequences give rise to deletions, duplications and inversions. Chromosome-specific LCRs on human chromosome 22q11 have been implicated in various constitutional rearrangements leading to genetic disease. Although the human 22q11 LCRs have been sequenced, very little is known about their evolution and amplification in the genome. Comparative analysis of the mouse genome has revealed an absence of LCRs at the orthologous loci. Examination of the 22q11 LCRs in non-human primates suggests that they have originated and evolved during primate evolution. We wish to investigate the mechanism responsible for chromosome-specific duplications and their role in the evolution of the primate genome. Toward this goal, we propose a comparative analysis of the organization and structure of the 22q11 LCRs in humans and non-human primates. We will analyze the 22q11 LCRs in various non-human primates at the chromosomal, gross structural and nucleotide sequence levels. The evolutionary analysis of the primate-specific 22q11 LCRs provide a unique opportunity to investigate the molecular mechanism underlying this form of genome evolution. We will also test the hypothesis that the processes responsible for the origin and spread of the chromosome-specific duplications are ongoing and may have resulted in genomic variability within the human population. We will perform a population-based analysis to look for genetic polymorphism in the structural organization of 22q11 LCRs within various human population groups. This will allow us to assess the involvement of LCRs in creating genetic variation that may lead to the genomic instability associated with human genetic disorders. Thus, the 22q11 LCRs provide a model system with which to gain a better understanding of the evolution of the human genome.

描述(申请人提供)：大规模基因复制 物质是推动遗传多样性进化的主要力量。基因 重复和随之而来的分歧在创造 具有特殊功能作用的新基因，这一过程一直很重要 用于创造进化多样性和物种形成。不断积累的 人类基因组序列揭示了一类基因组复制 是特定于染色体的。有趣的是，这些染色体特有的序列 复制或低拷贝重复(LCR)与许多 与复发性基因组有关的人类遗传性疾病 重新安排。有人提出，非法重组 由高度同源的重复序列促成的 删除、重复和倒置。人类染色体特异的LCRs 染色体22q11与各种组织结构重排有关。 导致遗传性疾病。虽然已经对人类22q11 LCR进行了测序， 人们对它们在基因组中的进化和放大知之甚少。 对小鼠基因组的比较分析表明，在 同源基因。对非人灵长类动物22q11 LCRs的检测表明 它们是在灵长类进化过程中起源和进化的。我们希望 研究染色体特异性复制的机制和 它们在灵长类基因组进化中的作用。为了实现这一目标，我们建议 22q11 LCRs组织结构的比较分析 人类和非人类灵长类动物。我们将分析22q11 LCR在不同的 非人灵长类的染色体、大体结构和核苷酸序列 级别。灵长类特异的22q11 LCR的进化分析提供了一个 研究这种形式背后的分子机制的独特机会 基因组进化论。我们还将检验这一假设 负责染色体特异性复制的起源和传播 正在进行中，可能导致了人类体内的基因组变异 人口。我们将进行基于种群的分析来寻找基因 不同人群22q11 LCRs结构组织的多态性 人口群体。这将使我们能够评估LCR在 创造遗传变异，可能导致相关的基因组不稳定 患有人类遗传病。因此，22q11 LCR为模型系统提供了 从而更好地了解人类基因组的进化。