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 Idaghdour, 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 journalArticlepeer-review


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
Issue number7
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'Variation in genome-wide mutation rates within and between human families'. Together they form a unique fingerprint.

Cite this