Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Am J Hum Genet. 2013 Sep 5;93(3):411-21. doi: 10.1016/j.ajhg.2013.07.002. Epub 2013 Aug 8.
A principal obstacle to completing maps and analyses of the human genome involves the genome's "inaccessible" regions: sequences (often euchromatic and containing genes) that are isolated from the rest of the euchromatic genome by heterochromatin and other repeat-rich sequence. We describe a way to localize these sequences by using ancestry linkage disequilibrium in populations that derive ancestry from at least three continents, as is the case for Latinos. We used this approach to map the genomic locations of almost 20 megabases of sequence unlocalized or missing from the current human genome reference (NCBI Genome GRCh37)-a substantial fraction of the human genome's remaining unmapped sequence. We show that the genomic locations of most sequences that originated from fosmids and larger clones can be admixture mapped in this way, by using publicly available whole-genome sequence data. Genome assembly efforts and future builds of the human genome reference will be strongly informed by this localization of genes and other euchromatic sequences that are embedded within highly repetitive pericentromeric regions.
完成人类基因组图谱和分析的主要障碍涉及基因组的“不可及”区域：这些序列（通常是常染色质，包含基因）通过异染色质和其他富含重复序列与常染色质基因组的其余部分隔离。我们描述了一种方法，通过利用至少来自三个大陆（如拉丁裔）的人群中的祖先连锁不平衡来定位这些序列。我们使用这种方法来绘制当前人类基因组参考（NCBI Genome GRCh37）中未定位或缺失的近 2000 万个碱基对序列的基因组位置——这是人类基因组剩余未映射序列的很大一部分。我们表明，大多数源自fosmid 和更大克隆的序列的基因组位置可以通过这种方式进行混合映射，使用公开可用的全基因组序列数据。基因组组装工作和人类基因组参考的未来构建将受到这种定位于高度重复着丝粒区域内的基因和其他常染色质序列的强烈影响。
