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

Donald F. Conrad, Jonathan E.M. Keebler, Mark A. Depristo, Sarah J. Lindsay, Yujun Zhang, Ferran Casals, Youssef Idaghdhour, Chris L. Hartl, Carlos Torroja, Kiran V. Garimella, Martine Zilversmit, Reed Cartwright, Guy A. Rouleau, Mark Daly, Eric A. Stone, Matthew E. Hurles, Philip Awadalla

Research output: Contribution to journalArticle

Abstract

J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline1. Diverse studies have supported Haldane's contention of a higher average mutation rate in the male germline in a variety of mammals, including humans. 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.

Original languageEnglish (US)
Pages (from-to)712-714
Number of pages3
JournalNature Genetics
Volume43
Issue number7
DOIs
StatePublished - Jul 1 2011

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Mutation Rate
Genome
Mutation
Germ-Line Mutation
Mammals
Mothers
Cell Line
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

Conrad, D. F., Keebler, J. E. M., Depristo, M. A., Lindsay, S. J., Zhang, Y., Casals, F., ... Awadalla, P. (2011). Variation in genome-wide mutation rates within and between human families. Nature Genetics, 43(7), 712-714. https://doi.org/10.1038/ng.862

Variation in genome-wide mutation rates within and between human families. / Conrad, Donald F.; Keebler, Jonathan E.M.; Depristo, Mark A.; Lindsay, Sarah J.; Zhang, Yujun; Casals, Ferran; Idaghdhour, Youssef; Hartl, Chris L.; Torroja, Carlos; Garimella, Kiran V.; Zilversmit, Martine; Cartwright, Reed; Rouleau, Guy A.; Daly, Mark; Stone, Eric A.; Hurles, Matthew E.; Awadalla, Philip.

In: Nature Genetics, Vol. 43, No. 7, 01.07.2011, p. 712-714.

Research output: Contribution to journalArticle

Conrad, DF, Keebler, JEM, Depristo, MA, Lindsay, SJ, Zhang, Y, Casals, F, Idaghdhour, Y, Hartl, CL, Torroja, C, Garimella, KV, Zilversmit, M, Cartwright, R, Rouleau, GA, Daly, M, Stone, EA, Hurles, ME & Awadalla, P 2011, 'Variation in genome-wide mutation rates within and between human families', Nature Genetics, vol. 43, no. 7, pp. 712-714. https://doi.org/10.1038/ng.862
Conrad DF, Keebler JEM, Depristo MA, Lindsay SJ, Zhang Y, Casals F et al. Variation in genome-wide mutation rates within and between human families. Nature Genetics. 2011 Jul 1;43(7):712-714. https://doi.org/10.1038/ng.862
Conrad, Donald F. ; Keebler, Jonathan E.M. ; Depristo, Mark A. ; Lindsay, Sarah J. ; Zhang, Yujun ; Casals, Ferran ; Idaghdhour, Youssef ; Hartl, Chris L. ; Torroja, Carlos ; Garimella, Kiran V. ; Zilversmit, Martine ; Cartwright, Reed ; Rouleau, Guy A. ; Daly, Mark ; Stone, Eric A. ; Hurles, Matthew E. ; Awadalla, Philip. / Variation in genome-wide mutation rates within and between human families. In: Nature Genetics. 2011 ; Vol. 43, No. 7. pp. 712-714.
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