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AJHG:身材矮小与基因组拷贝数变异有关

2011/11/30 来源:生物探索
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身高主要由家庭遗传下来,但科学家迄今只发现特定的基因特征,可解释大约10%的身高差异。

矮人有“侏儒”基因拷贝身高主要由家庭遗传下来,但科学家迄今只发现特定的基因特征,可解释大约10%的身高差异。

研究人员相信,在影响身高的遗传因素中,其中高达1半的部分归因于基因拷贝和DNA其它片段的丢失。

遗传异常,被称为拷贝数变异(CNV),是染色体上出现的变异,这意味着,细胞具有太多或太少DNA片段的拷贝数。

拷贝数变异的一些类型很常见,然而还存在一些类型,仅出现在少量人群中。

研究人员发现,很多不常见的CNV缺失(基因组的一部分丢失)出现在人体时,身材变矮小的趋势就很明显。

每个人的基因组都有至少一些缺失,一般有几千个DNA片段,有的甚至高达几百万个。

波士顿儿童医院的研究人员在两项研究中对共12000个人进行调查,发现:“每出现一百万个缺失时,人体的高度会相应减少八分之一英寸。”

Joel Hirschhorn 博士称:“研究表明,微弱、确定的关联出现在遗传物质丢失量和高度降低之间。”这项研究发表在《美国人类遗传学》(American Journal of Human Genetics)期刊上。

他补充道:“不管什么基因丢失,这一趋势都站得住脚。”

他还说:“从DNA序列中敲出一些碱基,大多数情况下没有任何效果,但在一些特殊情况下会有微弱影响。”

Genome-wide Association of Copy-Number Variation Reveals an Association between Short Stature and the Presence of Low-Frequency Genomic Deletions

Andrew Dauber  Yongguo Yu  Joel N. Hirschhorn

Height is a model polygenic trait that is highly heritable. Genome-wide association studies have identified hundreds of single-nucleotide polymorphisms associated with stature, but the role of structural variation in determining height is largely unknown. We performed a genome-wide association study of copy-number variation and stature in a clinical cohort of children who had undergone comparative genomic hybridization (CGH) microarray analysis for clinical indications. We found that subjects with short stature had a greater global burden of copy-number variants (CNVs) and a greater average CNV length than did controls (p < 0.002). These associations were present for lower-frequency (<5%) and rare (<1%) deletions, but there were no significant associations seen for duplications. Known gene-deletion syndromes did not account for our findings, and we saw no significant associations with tall stature. We then extended our findings into a population-based cohort and found that, in agreement with the clinical cohort study, an increased burden of lower-frequency deletions was associated with shorter stature (p = 0.015). Our results suggest that in individuals undergoing copy-number analysis for clinical indications, short stature increases the odds that a low-frequency deletion will be found. Additionally, copy-number variation might contribute to genetic variation in stature in the general population.

文献链接:http://www.cell.com/AJHG/abstract/S0002-9297%2811%2900448-4

 

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