Extended tracts of homozygosity in outbred human populations
Extended tracts of homozygosity in outbred human populations
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DOI：
10.1093/hmg/ddi493
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发表时间：
2006-03-01
影响因子：
3.5
通讯作者：
Collins, A
中科院分区：
文献类型：
--
作者：
Gibson, J;Morton, NE;Collins, A
长束连续的纯合单核苷酸多态性（snp）可以通过多种机制在基因组中产生。这些包括近亲繁殖，其中一个个体从每个亲本遗传相同的染色体片段。然而，重组和其他过程在几代人中破坏了染色体片段。因此，在具有相当程度近亲繁殖的种群中，可以预期最长的种群带。我们检查了纯合子长束的长度，数量和分布在明显近交的HapMap群体。我们在209个无亲缘关系的HapMap个体中观察到1393个束长度超过1mb。最长的是一个日本人的3922个纯合snp的不间断运行，跨度为17.9 Mb。我们发现纯合子束在高连锁不平衡和低重组的区域更为常见，并且在所有种群中束的位置相似。约鲁巴人的样本中每个个体的长链最少，这与自该群体建立以来的更大的世代数量（因此重组的数量）是一致的。我们的研究结果表明，在广泛的基因组区域中，远交人群中存在着多个兆级祖先单倍型，其重组率低于平均水平。我们观察到三个偏远的个体，他们有异常长的和大量的纯合束，这些纯合束与基因组的重组抑制区域无关。我们认为这反映了他们祖先的高度亲缘关系，这种亲缘关系太近了，不可能受到当地重组强度的影响。可能的替代机制和意义的长纯合子束在基因组进行了讨论。
Long tracts of consecutive homozygous single nucleotide polymorphisms (SNPs) can arise in the genome through a number of mechanisms. These include inbreeding in which an individual inherits chromosomal segments that are identical by descent from each parent. However, recombination and other processes break up chromosomal segments over generations. The longest tracts are therefore to be expected in populations with an appreciable degree of inbreeding. We examined the length, number and distribution of long tracts of homozygosity in the apparently outbred HapMap populations. We observed 1393 tracts exceeding 1 Mb in length among the 209 unrelated HapMap individuals. The longest was an uninterrupted run of 3922 homozygous SNPs spanning 17.9 Mb in a Japanese individual. We find that homozygous tracts are significantly more common in regions with high linkage disequilibrium and low recombination, and the location of tracts is similar across all populations. The Yoruba sample has the fewest long tracts per individual, consistent with a larger number of generations (and hence amount of recombination) since the founding of that population. Our results suggest that multiple-megabase-scale ancestral haplotypes persist in outbred human populations in broad genomic regions which have lower than average recombination rates. We observed three outlying individuals who have exceptionally long and numerous homozygous tracts that are not associated with recombination suppressed areas of the genome. We consider that this reflects a high level of relatedness in their ancestry which is too recent to have been influenced by the local recombination intensity. Possible alternative mechanisms and the implications of long homozygous tracts in the genome are discussed.