Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome
Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome
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DOI：
10.1038/ng1862
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发表时间：
2006-09-01
期刊：
影响因子：
30.8
通讯作者：
Eichler, Evan E.
中科院分区：
文献类型：
--
作者：
Sharp, Andrew J.;Hansen, Sierra;Eichler, Evan E.
基因组疾病的特征在于侧翼片段重复的存在，使这些区域易于发生复发性重排。基于基因组的重复结构，我们研究了130个区域，我们假设这些区域是以前未描述的基因组疾病的候选区域（1）。我们测试了290个人与精神发育迟滞BAC阵列比较基因组杂交，并确定了16个致病性重排，包括从头微缺失17q21.31发现在4个人。使用寡核苷酸阵列，我们完善了这个微缺失的断点，定义了一个478 kb的关键区域，包含6个基因，在所有4个人被删除。我们绘制了这个缺失的断点和1q21.1，15q13，15q24和17q12中的其他四个致病性重排的侧翼片段重复，这表明这些也是经常性重排的位点。与17q21.31缺失相同，这些断点区域是对照中拷贝数多态性的位点，表明这些可能是固有不稳定的基因组区域。
Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders(1). We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in four individuals. Using oligonucleotide arrays, we refined the breakpoints of this microdeletion, defining a 478-kb critical region containing six genes that were deleted in all four individuals. We mapped the breakpoints of this deletion and of four other pathogenic rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental duplications, suggesting that these are also sites of recurrent rearrangement. In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions.