A large and complex structural polymorphism at 16p12.1 underlies microdeletion disease risk.
A large and complex structural polymorphism at 16p12.1 underlies microdeletion disease risk.
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在与人类疾病相关的片段复制和重排的进化之间存在着复杂的关系。我们对与神经认知疾病相关的染色体16p12.1上的一个区域进行了详细分析，并确定了与人类参考组合最大的结构不一致之一。各种基因组分析表明，所有被检测的人在16p12.1上的1.1 mbp区域相对于参考基因组是纯合倒置的。我们确定这种装配差异源于两种常见的结构构型，其全球频率分别为17.6% （S1）和82.4% （S2）。这种多态性源于片段复制的快速整合，在过去的1000万年中，在人类谱系中引发了两次局部反转。这两种人类单倍型的不同之处在于，S2中有333kbp的额外重复序列，而S1中没有。重要的是，我们发现S2结构包含直接定向的重复，特别容易使这条染色体发生疾病重排。
There is a complex relationship between the evolution of segmental duplications and rearrangements associated with human disease. We performed a detailed analysis of one region on chromosome 16p12.1 associated with neurocognitive disease and identified one of the largest structural inconsistencies with the human reference assembly. Various genomic analyses show that all examined humans are homozygously inverted relative to the reference genome for a 1.1-Mbp region on 16p12.1. We determined that this assembly discrepancy stems from two common structural configurations with worldwide frequencies of 17.6% (S1) and 82.4% (S2). This polymorphism arose from the rapid integration of segmental duplications, precipitating two local inversions within the human lineage over the last 10 million years. The two human haplotypes differ by 333 kbp of additional duplicated sequence present in S2 but not in S1. Importantly, we show that the S2 configuration harbors directly oriented duplications specifically predisposing this chromosome to disease rearrangement.
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影响因子：
48
作者：
Craig, David W.;Pearson, John V.;Szelinger, Szabolcs;Sekar, Aswin;Redman, Margot;Corneveaux, Jason J.;Pawlowski, Traci L.;Laub, Trisha;Nunn, Gary;Stephan, Dietrich A.;Homer, Nils;Huentelman, Matthew J.
通讯作者：
Huentelman, Matthew J.
影响因子：
9.8
作者：
Church DM;Goodstadt L;Hillier LW;Zody MC;Goldstein S;She X;Bult CJ;Agarwala R;Cherry JL;DiCuccio M;Hlavina W;Kapustin Y;Meric P;Maglott D;Birtle Z;Marques AC;Graves T;Zhou S;Teague B;Potamousis K;Churas C;Place M;Herschleb J;Runnheim R;Forrest D;Amos-Landgraf J;Schwartz DC;Cheng Z;Lindblad-Toh K;Eichler EE;Ponting CP;Mouse Genome Sequencing Consortium
通讯作者：
Mouse Genome Sequencing Consortium
影响因子：
3.5
作者：
Antonacci F;Kidd JM;Marques-Bonet T;Ventura M;Siswara P;Jiang Z;Eichler EE
通讯作者：
Eichler EE
影响因子：
56.9
作者：
Bailey, JA;Gu, ZP;Eichler, EE
通讯作者：
Eichler, EE
影响因子：
9.8
作者：
Giglio, S;Broman, KW;Zuffardi, O
通讯作者：
Zuffardi, O