Molecular Extent of Linkage Disequilibrium

连锁不平衡的分子程度

• 批准号: 7585693
• 负责人: Kenneth K. KIDD
• 金额: $ 40.56万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7585693
• 关键词: 17q; 17q21; Affect; BRCA1 gene; Biological Assay; Biosensor; COL1A1 gene; Characteristics; DNA; Data Analyses; Databases; Family; Female; Frequencies; Future; Gel; Genes; Genetic Polymorphism; Genetic Recombination; Genome; Haplotypes; Human; Individual; Length; Linkage Disequilibrium; Maps; Methods; Molecular; NGFR gene; Numbers; Pattern; Population; Population Study; Qualifying; RARA gene; Rate; Scanning; Sex Characteristics; Side; Source; Testing; Variant; Work; base; concept; data management; density; design; human study; interest; male; type I collagen alpha 1

Project 2 focuses on the patterns of linkage disequilibrium across17q21, a 12 Mb long region of the genome with several interesting characteristics. First, it is a relatively gene rich region with 253 genes assigned in the latest assembly (Nov, '02), though there are a few regions that have no identified genes across several hundred kb. Second, there is considerable evidence that it contains at least one region that would qualify as a block with strong LD extending across many kb: the BRCA1 gene appears to be a "block"with LD across at least 81 kb; LD was detected across an even longer distance of 8.6 Mb between D17S1787 ad D17S943 in the CEPH families. Third, the recombination frequencies across the region, based on two large independent mapping studies (Marshfield and Decode) show a great sex difference: the recombination rate between D17S1818 and D17S1877, which just flank 17q21, is estimated at 4.29 and 4.94 cM, respectively, in males and at 24.01 and 17.33 cM, respectively, in females. Finally, although 17q has many low copy segmental duplications (inter- and intra-chromosomal) on either side of 17q21, this region is relatively free of such repeats and the sequence assembly is relatively unambiguous. We will examine this region with over 1000 markers spaced at approximately 10 kb intervals with closer spacing in especially gene-rich regions and somewhat sparser coverage in the gene poor regions. As the boundaries (if they exist as such) of putative blocks become evident, we will attempt to have denser coverage to better define the boundaries and the variation in those boundaries in different populations. All markers will be typed in about 2500 individuals representing at least 40 populations. Empirically, we will be able to determine how generalizable the patterns of LD are among the various populations. This will provide one test of the generalizability of the "haplotype map" concept. The patterns of LD in the different populations, the levels of heterozygosity, and the population relationships will all be used in analyses designed to estimate the multiple factors that are the causes of LD in modern humans.

项目2重点介绍了17q21的连锁不平衡的模式，这是该基因组的12 MB长区域，具有几个有趣的特征。首先，它是一个相对富含基因的区域，在最新组装中分配了253个基因（02年11月），尽管有几个区域在数百个KB中尚无鉴定基因。其次，有大量的证据表明，它至少包含一个区域，该区域有资格作为一个块，其强大的LD延伸到许多Kb：BRCA1基因似乎是一个“块”，其中LD至少为81 Kb；在CEPH家族的D17S1787 AD D17S943之间，在8.6 Mb的更长距离中检测到LD。第三，基于两项大型独立映射研究（Marshfield和Decode）的重组频率显示了很大的性别差异：D17S11818和D17S1877之间的重组率估计为4.29和4.29和4.94 CM分别为男性和24.01和17.33 cm的女性。最后，尽管17q在17q21的两侧具有许多低拷贝的分段重复（染色体内和染色体内），但该区域相对不含这种重复序列，并且序列组装相对明确。我们将检查该区域的区域以上超过1000个标记，以大约10 kb的间隔间隔，特别是富基因区域的间距，并且在基因较差的区域中的覆盖范围更为稀疏。随着推定块的边界（如果存在的话）变得明显，我们将尝试进行密集的覆盖范围，以更好地定义不同人群中这些边界的边界和差异。所有标记将在代表至少40个人群的大约2500个人中输入。从经验上讲，我们将能够确定LD的模式在各种人群中的普遍性。这将为“单倍型地图”概念的普遍性提供一个测试。不同的LD模式 种群，杂合性水平和人群关系的水平都将用于旨在估计现代人类LD原因的多种因素的分析中。