Landscape and variation of novel retroduplications in 26 human populations.
Landscape and variation of novel retroduplications in 26 human populations.
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DOI：
10.1371/journal.pcbi.1005567
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发表时间：
2017-06
影响因子：
4.3
通讯作者：
Gerstein MB
中科院分区：
文献类型：
--
作者：
Zhang Y;Li S;Abyzov A;Gerstein MB
Retroduplications come from reverse transcription of mRNAs and their insertion back into the genome. Here, we performed comprehensive discovery and analysis of retroduplications in a large cohort of 2,535 individuals from 26 human populations, as part of 1000 Genomes Phase 3. We developed an integrated approach to discover novel retroduplications combining high-coverage exome and low-coverage whole-genome sequencing data, utilizing information from both exon-exon junctions and discordant paired-end reads. We found 503 parent genes having novel retroduplications absent from the reference genome. Based solely on retroduplication variation, we built phylogenetic trees of human populations; these represent superpopulation structure well and indicate that variable retroduplications are effective population markers. We further identified 43 retroduplication parent genes differentiating superpopulations. This group contains several interesting insertion events, including a SLMO2 retroduplication and insertion into CAV3, which has a potential disease association. We also found retroduplications to be associated with a variety of genomic features: (1) Insertion sites were correlated with regular nucleosome positioning. (2) They, predictably, tend to avoid conserved functional regions, such as exons, but, somewhat surprisingly, also avoid introns. (3) Retroduplications tend to be co-inserted with young L1 elements, indicating recent retrotranspositional activity, and (4) they have a weak tendency to originate from highly expressed parent genes. Our investigation provides insight into the functional impact and association with genomic elements of retroduplications. We anticipate our approach and analytical methodology to have application in a more clinical context, where exome sequencing data is abundant and the discovery of retroduplications can potentially improve the accuracy of SNP calling. We developed an approach and performed comprehensive discovery of retroduplications from 26 human populations, utilizing whole-exome and whole-genome sequencing data. Our high-resolution landscape of retroduplications reveals that variable retroduplications are effective markers of human populations and can track population divergence. We observed that novel retroduplications come from genes with relatively high expression level and co-inserted L1 elements belong to young L1 families, indicating recent retroduplication activity in human migration contributing to genetic diversity. We have also detected several interesting intragenic insertion events, including SLMO2 retroduplication and insertion into CAV3, which worth further investigation for disease predisposition.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
7
作者：
Baller, Joshua A.;Gao, Jiquan;Voytas, Daniel F.
通讯作者：
Voytas, Daniel F.
DOI：
10.1038/nrg.2015.25
发表时间：
2016-04
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Carvalho CM;Lupski JR
通讯作者：
Lupski JR
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y