Insights about clonal hematopoiesis from 8,342 mosaic chromosomal alterations
The selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations (mCAs) of length 50kb–249Mb that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using new phase-based computational techniq...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
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Nature Publishing Group
2018
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| _version_ | 1826264096224313344 |
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| author | Loh, P Genovese, G Handsaker, R Finucane, H Reshef, Y Palamara, P Birmann, B Talkowski, M Bakhoum, S McCarroll, S Price, A |
| author_facet | Loh, P Genovese, G Handsaker, R Finucane, H Reshef, Y Palamara, P Birmann, B Talkowski, M Bakhoum, S McCarroll, S Price, A |
| author_sort | Loh, P |
| collection | OXFORD |
| description | The selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations (mCAs) of length 50kb–249Mb that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using new phase-based computational techniques (estimated false discovery rate, 6–9%). We found six loci at which inherited variants associated strongly with the acquisition of deletions or loss of heterozygosity in cis. At three such loci (MPL, TM2D3/TARSL2, and FRA10B), we identified a likely causal variant that acted with high penetrance (5–50%). Inherited alleles at one locus appeared to affect the probability of somatic mutation, and at three other loci to be objects of positive or negative clonal selection. Several specific mCAs strongly associated with future hematological malignancies. Our results reveal a multitude of paths toward clonal expansions with a wide range of effects on human health. |
| first_indexed | 2024-03-06T20:02:17Z |
| format | Journal article |
| id | oxford-uuid:27b822a0-d3ca-42be-854d-935173305101 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T20:02:17Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:27b822a0-d3ca-42be-854d-9351733051012022-03-26T12:08:33ZInsights about clonal hematopoiesis from 8,342 mosaic chromosomal alterationsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:27b822a0-d3ca-42be-854d-935173305101Symplectic Elements at OxfordNature Publishing Group2018Loh, PGenovese, GHandsaker, RFinucane, HReshef, YPalamara, PBirmann, BTalkowski, MBakhoum, SMcCarroll, SPrice, AThe selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations (mCAs) of length 50kb–249Mb that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using new phase-based computational techniques (estimated false discovery rate, 6–9%). We found six loci at which inherited variants associated strongly with the acquisition of deletions or loss of heterozygosity in cis. At three such loci (MPL, TM2D3/TARSL2, and FRA10B), we identified a likely causal variant that acted with high penetrance (5–50%). Inherited alleles at one locus appeared to affect the probability of somatic mutation, and at three other loci to be objects of positive or negative clonal selection. Several specific mCAs strongly associated with future hematological malignancies. Our results reveal a multitude of paths toward clonal expansions with a wide range of effects on human health. |
| spellingShingle | Loh, P Genovese, G Handsaker, R Finucane, H Reshef, Y Palamara, P Birmann, B Talkowski, M Bakhoum, S McCarroll, S Price, A Insights about clonal hematopoiesis from 8,342 mosaic chromosomal alterations |
| title | Insights about clonal hematopoiesis from 8,342 mosaic chromosomal alterations |
| title_full | Insights about clonal hematopoiesis from 8,342 mosaic chromosomal alterations |
| title_fullStr | Insights about clonal hematopoiesis from 8,342 mosaic chromosomal alterations |
| title_full_unstemmed | Insights about clonal hematopoiesis from 8,342 mosaic chromosomal alterations |
| title_short | Insights about clonal hematopoiesis from 8,342 mosaic chromosomal alterations |
| title_sort | insights about clonal hematopoiesis from 8 342 mosaic chromosomal alterations |
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