Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.
Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.
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通过 SNP 微阵列在可能患有威廉姆斯综合征的智力障碍个体中检测到基因组重排。
DOI：
10.1371/journal.pone.0012349
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发表时间：
2010-08-31
期刊：
影响因子：
3.7
通讯作者：
Gregg, Ronald G.
中科院分区：
文献类型：
--
作者：
Pani, Ariel M.;Hobart, Holly H.;Morris, Colleen A.;Mervis, Carolyn B.;Bray-Ward, Patricia;Kimberley, Kendra W.;Rios, Cecilia M.;Clark, Robin C.;Gulbronson, Maricela D.;Gowans, Gordon C.;Gregg, Ronald G.
智力残疾（ID）影响2-3%的人口，可能伴有或不伴有多种先天性异常（MCA）或其他医疗条件。已确定的遗传综合征和可见的染色体异常占ID诊断的相当大的比例，尽管约50%的分子病因是未知的。具有提示各种综合征特征但缺乏相关遗传异常的个体构成了巨大的临床挑战。随着微阵列技术的出现，与已知综合征无关的亚微观基因组改变正在成为ID和MCA的重要原因。高密度SNP微阵列被用于确定42个个体的全基因组拷贝数：7个在WS区域具有确认的改变但具有非典型临床表型，31个具有ID和/或MCA，以及4个对照。来自第一组的一个个体在WS关键区中具有最端粒的基因，其缺失沿着2 Mb的侧翼序列。第二个人在Cri du Chat综合征（OMIM：123450）区域内的染色体5 p上有经典的WS缺失和重排。来自ID/MCA组的六个个体具有大的重排（3个缺失，3个重复），其中一个具有与SNP阵列未检测到的缺失相关的大倒位。结合SNP微阵列分析和qPCR允许我们克隆和测序在WS区域和/或ID或MCA中具有非典型缺失的个体中的21个缺失断点。将这些断点与基因组变异数据库进行比较，发现52%发生在一般人群中含有结构变异的区域。对于两个先证者的基因组改变两侧的片段重复，这往往介导复发的基因组重排，这些可能代表新的基因组疾病。虽然SNP阵列和相关技术可以识别潜在的致病性缺失和重复，但从断点获得序列信息通常可以提供额外的信息。
Intellectual disability (ID) affects 2–3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for ∼50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA. High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays. Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
4
作者：
Edelmann, Lisa;Prosnitz, Aaron;McInnes, L. Alison
通讯作者：
McInnes, L. Alison
DOI：
10.1002/ajmg.c.30258
发表时间：
2010-05-15
影响因子：
3.1
作者：
Hobart, Holly H.;Morris, Colleen A.;Bray-Ward, Patricia
通讯作者：
Bray-Ward, Patricia
影响因子：
9.8
作者：
Friedman, J. M.;Baross, Agnes;Marra, Marco A.
通讯作者：
Marra, Marco A.