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

J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline. 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 fir...

Full description

Saved in:
Bibliographic Details
Published inNature genetics Vol. 43; no. 7; pp. 712 - 714
Main Authors CONRAD, Donald F, KEEBLER, Jonathan E. M, ZILVERSMIT, Martine, CARTWRIGHT, Reed, ROULEAU, Guy A, DALY, Mark, STONE, Eric A, HURLES, Matthew E, AWADALLA, Philip, DEPRISTO, Mark A, LINDSAY, Sarah J, YUJUN ZHANG, CASALS, Ferran, IDAGHDOUR, Youssef, HARTL, Chris L, TORROJA, Carlos, GARIMELLA, Kiran V
Format Journal Article
LanguageEnglish
Published New York, NY Nature Publishing Group 01.07.2011
Subjects
Algorithms
Biological and medical sciences
Chromosome Mapping
Confidence intervals
DNA Mutational Analysis
Estimates
Evolution
Family
Female
Fundamental and applied biological sciences. Psychology
Gene mutations
Genetic aspects
Genetic Variation
Genetics of eukaryotes. Biological and molecular evolution
Genome, Human
Genomes
Germ-Line Mutation - genetics
Humans
Male
Methods
Mutation
Physiological aspects
Polymerase Chain Reaction
United States
Human
Mutation
Online AccessGet full text

Cover

More Information
Summary:J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline. 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Full listing of authors and affiliations in Supplementary Note
ISSN:1061-4036
1546-1718
DOI:10.1038/ng.862