Cited by 584Genomics and Rare DiseasesGenomics and Phylogenetic StudiesGenomic variations and chromosomal abnormalities

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

Open access
the 1000 Genomes Project·2011·Nature Genetics

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ng.862

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The genome-wide rate of nucleotide substitutions is estimated at 30-100 per generation, with about one per exome.

    “The rate of nucleotide substitutions genome-wide is estimated at 30–100 per generation (Conrad et al., 2011) and ~1 per exome.”

    From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Conrad et al., 2011

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 20 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
the 1000 Genomes Project
Affiliations
Wellcome Sanger Institute (GB)
Corresponding author
the 1000 Genomes Project
Venue
Nature Genetics
Published
2011-06-12
Volume
43
Issue
7
Pages
712-714
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2004209173
Cited by
581
References
20
Citations by year
2026: 14 · 2025: 22 · 2024: 21 · 2023: 19 · 2022: 31 · 2021: 21 · 2020: 20 · 2019: 36 · 2018: 63 · 2017: 42 · 2016: 46 · 2015: 54 · 2014: 51 · 2013: 55 · 2012: 67
FWCI
38.11
Type
journal article
Language
en
Open access
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust (085532, 077014, 090532, 077014/Z/05/Z)
  • National Institute of General Medical Sciences (R01GM070806)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
germline mutation rate, de novo mutations, Haldane's rule, parent-offspring trios, somatic mutations, 1000 Genomes Project
MeSH terms
Chromosome Mapping, DNA Mutational Analysis, Family, Female, Humans, Male, Genetic Variation, Genome, Human, Polymerase Chain Reaction, Germ-Line Mutation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review