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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