Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 60,207 bioRxiv papers from 267,649 authors.

Extremely rare variants reveal patterns of germline mutation rate heterogeneity in humans

By Jedidiah Carlson, Adam E. Locke, Matthew Flickinger, Matthew Zawistowski, Shawn Levy, The BRIDGES Consortium, Richard M. Myers, Michael Boehnke, Hyun Min Kang, Laura J. Scott, Rolf Kuemmerli, Sebastian Zöllner

Posted 14 Feb 2017
bioRxiv DOI: 10.1101/108290 (published DOI: 10.1038/s41467-018-05936-5)

A detailed understanding of the genome-wide variability of single-nucleotide germline mutation rates is essential to studying human genome evolution. Here we use ~36 million singleton variants from 3,560 whole-genome sequences to infer fine-scale patterns of mutation rate heterogeneity. Mutability is jointly affected by adjacent nucleotide context and diverse genomic features of the surrounding region, including histone modifications, replication timing, and recombination rate, sometimes suggesting specific mutagenic mechanisms. Remarkably, GC content, DNase hypersensitivity, CpG islands, and H3K36 trimethylation are associated with both increased and decreased mutation rates depending on nucleotide context. We validate these estimated effects in an independent dataset of ~46,000 de novo mutations, and confirm our estimates are more accurate than previously published estimates based on ancestrally older variants without considering genomic features. Our results thus provide the most refined portrait to date of the factors contributing to genome-wide variability of the human germline mutation rate.

Download data

  • Downloaded 1,740 times
  • Download rankings, all-time:
    • Site-wide: 2,733 out of 60,207
    • In genomics: 555 out of 4,168
  • Year to date:
    • Site-wide: 37,865 out of 60,207
  • Since beginning of last month:
    • Site-wide: 51,349 out of 60,207

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News