Copy number variations at the Prader-Willi syndrome region on chromosome 15 and associations with obesity in whites.
Copy number variations at the Prader-Willi syndrome region on chromosome 15 and associations with obesity in whites.
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DOI：
10.1038/oby.2010.323
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Deng HW
中科院分区：
文献类型：
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作者：
Chen Y;Liu YJ;Pei YF;Yang TL;Deng FY;Liu XG;Li DY;Deng HW
肥胖是一个严重的健康问题，具有很强的遗传决定性。拷贝数变异（Copy number variation，CNV）是一种常见的基因组变异类型，与一些复杂的人类疾病相关。然而，目前尚不清楚CNV如何导致肥胖的病因。在这项研究中，我们检查了1,000名无关的美国白人，以寻找可能导致肥胖的CNV。我们将我们的分析集中在Prader-Willi综合征（PWS）的关键区域（染色体15 q11-q13），因为PWS区域是CNV产生的热点，肥胖是该区域染色体异常的主要临床表现之一。我们构建了一个包含39个CNV的PWS关键区域的地图，CNV发生率高于1%。其中3个拷贝数与体脂量显著相关（P < 0.05），拷贝数越高，体脂量增加5.08- 9.77kg。这三个CNV与两个已知的PWS基因NDN（necdin homolog）和C15 orf 2（15号染色体开放阅读框2）接近，并且与另一个肥胖基因PWRN 1（Prader-Willi region nonprotein-coding RNA 1）部分重叠。有趣的是，我们最近发表的全基因组关联扫描研究使用相同的样本，通过检查单核苷酸多态性（SNPs）没有发现任何显着的关联在这些CNV区域，这表明检查CNVs和SNPs的重要性，以更好地了解肥胖的遗传基础。需要进一步的研究来验证这些CNV及其对肥胖的重要性。
Obesity is a serious health problem with strong genetic determination. Copy number variation (CNV) is a common type of genomic variant associated with some complex human diseases. However, it is not clear how CNVs contribute to the etiology of obesity. In this study, we examined 1,000 unrelated US whites to search for CNVs that may predispose to obesity. We focused our analyses on the Prader–Willi syndrome (PWS) critical region (chromosome 15q11–q13), because the PWS region is a hotspot for CNV generation and obesity is one of the major clinical manifestations for chromosome abnormalities at this region. We constructed a map containing 39 CNVs at the PWS critical region with CNV occurrence rates higher than 1%. Among them, three CNVs were significantly associated with body fat mass (P < 0.05), with a higher copy number (CN) associated with an increase of 5.08–9.77 kg in body fat mass. These three CNVs are close to two known PWS genes, NDN (necdin homolog) and C15orf2 (chromosome 15 open reading frame 2), and partially overlap with another obesity gene PWRN1 (Prader–Willi region nonprotein-coding RNA 1). Interestingly, our recently published whole genome association scan study using the same sample by examining single-nucleotide polymorphisms (SNPs) did not find any significant associations at these CNV regions, suggesting the importance of examining both CNVs and SNPs for better understanding of genetic basis of obesity. Further studies are warranted to validate these CNVs and their importance to obesity.