Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,822 bioRxiv papers from 266,142 authors.
Clonally expanded blood cells with somatic mutations (clonal hematopoiesis, CH) are commonly acquired with age and increase risk of later blood cancer. To identify genes and mutations that give selective advantage to mutant clones, we identified among 482,789 UK Biobank participants some 19,632 autosomal mosaic chromosomal alterations (mCAs), including deletions, duplications, and copy number-neutral loss of heterozygosity (CNN-LOH). Analysis of these acquired mutations, along with inherited genetic variation, revealed 52 inherited, rare, large-effect coding or splice variants (in seven genes) that greatly (odds ratios of 11 to 758) increased vulnerability to CH with specific acquired CNN-LOH mutations. Acquired mutations systematically replaced the inherited risk alleles (at MPL ) or duplicated them to the homologous chromosome (at FH , NBN , MRE11 , ATM , SH2B3 , and TM2D3 ). Three of the seven genes ( MRE11 , NBN , and ATM ) encode components of the MRN-ATM pathway, which limits cell division after DNA damage and telomere attrition; another two ( MPL , SH2B3 ) encode proteins that regulate stem cell self-renewal. In addition to these monogenic inherited forms of CH, we found a common and surprisingly polygenic form: CNN-LOH mutations across the genome tended to cause chromosomal segments with alleles that promote hematopoietic cell proliferation to replace their homologous (allelic) counterparts, increasing polygenic drive for blood-cell proliferation traits. This dynamic reveals a challenge for lifelong cytopoiesis in any genetically diverse species: individuals inherit unequal proliferative genetic potentials on paternally and maternally derived chromosome-pairs, and readily-acquired mutations that replace chromosomal segments with their homologous counterparts give selective advantage to mutant cells.
- Downloaded 688 times
- Download rankings, all-time:
- Site-wide: 11,498 out of 57,822
- In genetics: 827 out of 3,318
- Year to date:
- Site-wide: 2,106 out of 57,822
- Since beginning of last month:
- Site-wide: 4,243 out of 57,822
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!