Pedigree-based estimation of human mobile element retrotransposition rates
| Autor: | Hong-Seok Ha, Lisa Baird, Julie Feusier, Andrew Farrell, Jinchuan Xing, Jainy Thomas, Lynn B. Jorde, W. Scott Watkins, David J. Witherspoon |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Retroelements Alu element Retrotransposon Pedigree chart Biology Polymorphism Single Nucleotide Germline 03 medical and health sciences 0302 clinical medicine Germline mutation Alu Elements Phylogenetics Genetics Animals Humans Phylogeny Genetics (clinical) 030304 developmental biology Whole genome sequencing 0303 health sciences Whole Genome Sequencing Phylogenetic tree Research Hominidae Pedigree Interspersed Repetitive Sequences Long Interspersed Nucleotide Elements Mutation Mutation (genetic algorithm) Female 030217 neurology & neurosurgery |
| Zdroj: | Genome Research. 29:1567-1577 |
| ISSN: | 1549-5469 1088-9051 |
| Popis: | Germline mutation rates in humans have been estimated for a variety of mutation types, including single-nucleotide and large structural variants. Here, we directly measure the germline retrotransposition rate for the three active retrotransposon elements: L1, Alu, and SVA. We used three tools for calling mobile element insertions (MEIs) (MELT, RUFUS, and TranSurVeyor) on blood-derived whole-genome sequence (WGS) data from 599 CEPH individuals, comprising 33 three-generation pedigrees. We identified 26 de novo MEIs in 437 births. The retrotransposition rate estimates for Alu elements, one in 40 births, is roughly half the rate estimated using phylogenetic analyses, a difference in magnitude similar to that observed for single-nucleotide variants. The L1 retrotransposition rate is one in 63 births and is within range of previous estimates (1:20–1:200 births). The SVA retrotransposition rate, one in 63 births, is much higher than the previous estimate of one in 900 births. Our large, three-generation pedigrees allowed us to assess parent-of-origin effects and the timing of insertion events in either gametogenesis or early embryonic development. We find a statistically significant paternal bias in Alu retrotransposition. Our study represents the first in-depth analysis of the rate and dynamics of human retrotransposition from WGS data in three-generation human pedigrees. |
| Databáze: | OpenAIRE |
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