Recurrent Inversion Events at 17q21.31 Microdeletion Locus Are Linked to the MAPT H2 Haplotype
Recurrent Inversion Events at 17q21.31 Microdeletion Locus Are Linked to the MAPT H2 Haplotype
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DOI：
10.1159/000315901
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发表时间：
2010-01-01
影响因子：
1.7
通讯作者：
Ophoff, R. A.
中科院分区：
文献类型：
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作者：
Rao, P. N.;Li, W.;Ophoff, R. A.
染色体带17q21.31含有微管相关蛋白tau（MAPT）基因，是染色体重排的热点。已知在具有欧洲血统的人群中含有约900 kb的常见倒位多态性。倒置的构型与一种独特的MAPT单倍型H2有关，H2在欧洲人中相对常见，但在亚洲和非洲人群中几乎不存在。最近的研究表明，H2单倍型是原始人类的祖先，在欧洲人中处于正选择下。这种单倍型也与导致17q21.31微缺失综合征的事件有关，17q21.31微缺失综合征是欧洲人后裔中“特发性”精神发育迟滞的最常见原因之一。我们进行了直接分析的染色体结构的荧光原位杂交和观察杂合性的倒位状态的H2染色体，但不是H1单倍型。在H2单倍型纯合子的母亲中也观察到倒位杂合性，该母亲将缺失的染色体传递给17q21.31微缺失综合征的先证者。我们的研究结果突出了等位基因特异性的染色体重排的敏感性，并建议这是倒位状态的杂合性，易患17q21.31微缺失综合征。版权所有（C）2010 S. Karger AG，巴塞尔
The chromosomal band 17q21.31, containing the microtubule-associated protein tau (MAPT) gene, is a hotspot for chromosomal rearrangements. It is known to contain a common inversion polymorphism of approximately 900 kb in populations with European ancestry. The inverted configuration is linked to a distinct MAPT haplotype, H2, which is relatively common in Europeans but nearly absent in Asian and African populations. Recent studies have demonstrated that the H2 haplotype is ancestral in hominoids, and under positive selection in Europeans. This haplotype is also linked to events leading to the 17q21.31 microdeletion syndrome, one of the most common causes of 'idiopathic' mental retardation in people of European descent. We performed direct analysis of the chromosome structure by fluorescence in situ hybridization and observed heterozygosity of the inversion status for the H2 chromosomes, but not for the H1 haplotype. Inversion heterozygosity was also observed in a mother homozygous for the H2 haplotype, who transmitted the chromosome with the deletion to a proband with 17q21.31 microdeletion syndrome. Our results highlight an allele-specific sensitivity to chromosome rearrangements and suggest that it is the heterozygosity of inversion status that predisposes to the 17q21.31 microdeletion syndrome. Copyright (C) 2010 S. Karger AG, Basel