要了解遺傳因素對(duì)人類(lèi)疾病的影響，我們需要人群中功能性基因變化的豐度和分布的有關(guān)信息,。稀有遺傳變體可增加復(fù)雜疾病的風(fēng)險(xiǎn),，然而人類(lèi)群體中稀有遺傳變體的豐度仍不清楚。
Science雜志5月17日在線發(fā)表了Matthew R. Nelson等人的研究報(bào)告“An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People”,。進(jìn)一步解答了這一問(wèn)題,。
研究者對(duì)14,002個(gè)人類(lèi)個(gè)體的202個(gè)藥物靶點(diǎn)編碼基因進(jìn)行測(cè)序，以研究這些基因變化的范圍,。他們發(fā)現(xiàn),，稀有遺傳變體的豐度為每17個(gè)堿基出現(xiàn)一個(gè)，且呈地域局限性,。因此,，即使以大數(shù)量樣本進(jìn)行調(diào)查，對(duì)稀有變體的編目記載仍很不完善,。Matthew R. Nelson等利用已觀察到的基因變體模式估計(jì)這些變體在人群中的增長(zhǎng)參數(shù),，并估算有害基因變體在一定頻率級(jí)中所占的比例，以及每一個(gè)基因的突變率,。
最終,，他們得出結(jié)論認(rèn)為，由于快速的人口增長(zhǎng)和較弱的純化選擇,，人類(lèi)群體目前具有大量的稀有基因變體。這其中相當(dāng)一部分都是有害的,，與已知疾病的風(fēng)險(xiǎn)存在相關(guān)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.
