Copy-number variations measured by single-nucleotide polymorphism oligonucleotide Arrays in patients with mental retardation
Copy-number variations measured by single-nucleotide polymorphism oligonucleotide Arrays in patients with mental retardation
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DOI：
10.1086/521274
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发表时间：
2007-10-01
影响因子：
9.8
通讯作者：
Strom, Tim M.
中科院分区：
文献类型：
--
作者：
Wagenstaller, Janine;Spranger, Stephanie;Strom, Tim M.
使用高密度单核苷酸多态性寡核苷酸阵列的全基因组分析允许鉴定微缺失、微重复和单亲二体。我们研究了67名儿童不明原因的精神发育迟滞与正常的核型，作为评估的G显带染色体分析。用Affyestrium 100 K阵列分析它们的DNA。我们检测到11个拷贝数变异，最有可能是精神发育迟滞的原因，因为他们要么出现从头（9例）和/或与已知的微缺失重叠（2例）。8个缺失和3个重复的大小从200 kb到7.5 Mb不等。在11个拷贝数变异中，有5个侧翼为低拷贝重复序列。其中两个，在染色体15q25.2和Xp22.31，以前没有被描述过，并有很高的概率是新的缺失和重复综合征的原因，分别。在一名患者中，我们发现一个缺失只影响一个基因，MBD 5，它编码甲基CpG结合结构域蛋白5。除了67名儿童，我们调查了4名弱智儿童与明显的平衡易位，并检测到4个断点区域的大小从1.1到14 Mb的缺失。
Whole-genome analysis using high-density single-nucleotide-polymorphism oligonucleotide arrays allows identification of microdeletions, microduplications, and uniparental disomies. We studied 67 children with unexplained mental retardation with normal karyotypes, as assessed by G-banded chromosome analyses. Their DNAs were analyzed with Affymetrix 100K arrays. We detected 11 copy-number variations that most likely are causative of mental retardation, because they either arose de novo (9 cases) and/or overlapped with known microdeletions (2 cases). The eight deletions and three duplications varied in size from 200 kb to 7.5 Mb. Of the 11 copy-number variations, 5 were flanked by low-copy repeats. Two of those, on chromosomes 15q25.2 and Xp22.31, have not been described before and have a high probability of being causative of new deletion and duplication syndromes, respectively. In one patient, we found a deletion affecting only a single gene, MBD5, which codes for the methyl-CpG-binding domain protein 5. In addition to the 67 children, we investigated 4 mentally retarded children with apparent balanced translocations and detected four deletions at breakpoint regions ranging in size from 1.1 to 14 Mb.