Copy number variants in obesity-related syndromes: review and perspectives on novel molecular approaches.
Copy number variants in obesity-related syndromes: review and perspectives on novel molecular approaches.
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DOI：
10.1155/2012/845480
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发表时间：
2012
影响因子：
3.3
通讯作者：
Koiffmann CP
中科院分区：
文献类型：
--
作者：
D'Angelo CS;Koiffmann CP
近几十年来，肥胖症在世界范围内已达到流行病的程度，并成为公共卫生的一个主要问题。尽管遗传力估计为 40% 至 70%，并且在许多罕见病例中肥胖的遗传基础早已得到认可，但目前发表的全基因组关联研究 (GWAS) 列出的常见肥胖易感性变异列表仅解释了肥胖风险个体差异的一小部分。直到最近，具有极端表型的个体的拷贝数变异 (CNV) 的 GWAS 报告称，许多大型且罕见的 CNV 会导致肥胖的高风险，特别是染色体 16p11.2 上的缺失。在本文中，我们评论了肥胖遗传学领域的最新进展，重点关注与发育障碍相关的高渗透性肥胖形式所涉及的基因和基因组区域。该患者群体中的阵列基因组杂交为以前无法检测到的 CNV 提供了发现机会。这些信息可用于生成新的诊断阵列和测序平台，这可能会增强对已知遗传状况的检测，并有可能阐明新的疾病基因，并最终有助于开发与临床实践相关的下一代测序方案。
In recent decades, obesity has reached epidemic proportions worldwide and became a major concern in public health. Despite heritability estimates of 40 to 70% and the long-recognized genetic basis of obesity in a number of rare cases, the list of common obesity susceptibility variants by the currently published genome-wide association studies (GWASs) only explain a small proportion of the individual variation in risk of obesity. It was not until very recently that GWASs of copy number variants (CNVs) in individuals with extreme phenotypes reported a number of large and rare CNVs conferring high risk to obesity, and specifically deletions on chromosome 16p11.2. In this paper, we comment on the recent advances in the field of genetics of obesity with an emphasis on the genes and genomic regions implicated in highly penetrant forms of obesity associated with developmental disorders. Array genomic hybridization in this patient population has afforded discovery opportunities for CNVs that have not previously been detectable. This information can be used to generate new diagnostic arrays and sequencing platforms, which will likely enhance detection of known genetic conditions with the potential to elucidate new disease genes and ultimately help in developing a next-generation sequencing protocol relevant to clinical practice.