Variation in genome-wide mutation rates within and between human families

被引：396

作者：

Conrad, Donald F. ^{[2
,3
]}

Keebler, Jonathan E. M. ^{[1
,4
]}

DePristo, Mark A. ^{[5
]}

Lindsay, Sarah J. ^{[2
]}

Zhang, Yujun ^{[2
]}

Casals, Ferran ^{[1
]}

Idaghdour, Youssef ^{[1
]}

Hartl, Chris L. ^{[5
]}

Torroja, Carlos ^{[2
]}

Garimella, Kiran V. ^{[5
]}

Zilversmit, Martine ^{[1
]}

Cartwright, Reed ^{[6
]}

Rouleau, Guy A. ^{[7
]}

Daly, Mark ^{[5
]}

Stone, Eric A. ^{[4
,6
]}

Hurles, Matthew E. ^{[2
]}

Awadalla, Philip ^{[1
]}

机构：

[1] Univ Montreal, Fac Med, Dept Pediat, Ste Justine Hosp Res Ctr, Montreal, PQ H3C 3J7, Canada

[2] Wellcome Trust Sanger Inst, Cambridge, England

[3] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[4] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA

[5] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA

[6] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA

[7] Univ Montreal, Fac Med, Dept Med, Ste Justine Hosp Res Ctr, Montreal, PQ H3C 3J7, Canada

来源：

NATURE GENETICS | 2011年 / 43卷 / 07期

基金：

英国惠康基金;

关键词：

NUCLEOTIDE;

D O I：

10.1038/ng.862

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline(1). Diverse studies have supported Haldane's contention of a higher average mutation rate in the male germline in a variety of mammals, including humans(2,3). Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families.

引用

页码：712 / U137

页数：4

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