要了解遗传因素对人类疾病的影响，我们需要人群中功能性基因变化的丰度和分布的有关信息。稀有遗传变体可增加复杂疾病的风险，然而人类群体中稀有遗传变体的丰度仍不清楚。
Science杂志5月17日在线发表了Matthew R. Nelson等人的研究报告“An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People”。进一步解答了这一问题。
研究者对14,002个人类个体的202个药物靶点编码基因进行测序，以研究这些基因变化的范围。他们发现，稀有遗传变体的丰度为每17个碱基出现一个，且呈地域局限性。因此，即使以大数量样本进行调查，对稀有变体的编目记载仍很不完善。Matthew R. Nelson等利用已观察到的基因变体模式估计这些变体在人群中的增长参数，并估算有害基因变体在一定频率级中所占的比例，以及每一个基因的突变率。
最终，他们得出结论认为，由于快速的人口增长和较弱的纯化选择，人类群体目前具有大量的稀有基因变体。这其中相当一部分都是有害的，与已知疾病的风险存在相关性。（生物谷Bioon.com）
doi:10.1126/science.1217876
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PMID:
An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People
Matthew R. Nelson, Daniel Wegmann, Margaret G. Ehm, Darren Kessner, Pamela St. Jean, Claudio Verzilli1, Judong Shen, Zhengzheng Tang, Silviu-Alin Bacanu1, Dana Fraser1, Liling Warren, Jennifer Aponte, Matthew Zawistowski, Xiao Liu, Hao Zhang, Yong Zhang, Jun Li, Yun Li, Li Li1, Peter Woollard1, Simon Topp1, Matthew D. Hall, Keith Nangle, Jun Wang, Gonalo Abecasis, Lon R. Cardon1, Sebastian Zllner, John C. Whittaker, Stephanie L. Chissoe, John Novembre, Vincent Mooser
Rare genetic variants contribute to complex disease risk; however, the abundance of rare variants in human populations remains unknown. We explored this spectrum of variation by sequencing 202 genes encoding drug targets in 14,002 individuals. We find rare variants are abundant (one every 17 bases) and geographically localized, such that even with large sample sizes, rare variant catalogs will be largely incomplete. We used the observed patterns of variation to estimate population growth parameters, the proportion of variants in a given frequency class that are putatively deleterious, and mutation rates for each gene. Overall, we conclude that, due to rapid population growth and weak purifying selection, human populations harbor an abundance of rare variants, many of which are deleterious and have relevance to understanding disease risk.
