Molecular Extent of Linkage Disequilibrium

项目2侧重于ss17q21的连锁不平衡模式，这是一个12 Mb长的基因组区域，具有几个有趣的特征。首先，它是一个基因相对丰富的区域，在最近的组装中有253个基因被分配（2002年11月），尽管有几个区域在几百kb中没有确定的基因。其次，有相当多的证据表明，它包含至少一个区域，可以作为一个具有许多kb的强LD的块：BRCA1基因似乎是一个具有至少81 kb的LD的“块”；在CEPH家族的D17S1787和D17S943之间检测到的LD距离甚至更远，为8.6 Mb。第三，基于两个大型独立测绘研究（Marshfield和Decode），整个地区的重组频率显示出巨大的性别差异：D17S1818和D17S1877之间的重组率估计为4.29和4.94，而D17S1818刚好位于17q21旁边

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.