Detecting Non-allelic Homologous Recombination from High-throughput Sequencing Data

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2015 Apr 18

PMID 25886137

Citations 29

Authors

Matthew M Parks

Charles E Lawrence

Benjamin J Raphael

Affiliations

Soon will be listed here.

Abstract

Non-allelic homologous recombination (NAHR) is a common mechanism for generating genome rearrangements and is implicated in numerous genetic disorders, but its detection in high-throughput sequencing data poses a serious challenge. We present a probabilistic model of NAHR and demonstrate its ability to find NAHR in low-coverage sequencing data from 44 individuals. We identify NAHR-mediated deletions or duplications in 109 of 324 potential NAHR loci in at least one of the individuals. These calls segregate by ancestry, are more common in closely spaced repeats, often result in duplicated genes or pseudogenes, and affect highly studied genes such as GBA and CYP2E1.

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References

Levy A, Hochberg I, Jablonski K, Resnick H, Lee E, Best L . Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Cardiol. 2002; 40(11):1984-90. DOI: 10.1016/s0735-1097(02)02534-2. View

Chen Z, Yang H, Pavletich N . Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structures. Nature. 2008; 453(7194):489-4. DOI: 10.1038/nature06971. View

Gu W, Zhang F, Lupski J . Mechanisms for human genomic rearrangements. Pathogenetics. 2008; 1(1):4. PMC: 2583991. DOI: 10.1186/1755-8417-1-4. View

Medvedev P, Fiume M, Dzamba M, Smith T, Brudno M . Detecting copy number variation with mated short reads. Genome Res. 2010; 20(11):1613-22. PMC: 2963824. DOI: 10.1101/gr.106344.110. View

Kircher M, Heyn P, Kelso J . Addressing challenges in the production and analysis of illumina sequencing data. BMC Genomics. 2011; 12:382. PMC: 3163567. DOI: 10.1186/1471-2164-12-382. View

Jin T, Guo F, Wang Y, Zhang Y . High-resolution crystal structure of human Dim2/TXNL4B. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013; 69(Pt 3):223-7. PMC: 3606563. DOI: 10.1107/S1744309113000973. View

Lupski J . Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 1998; 14(10):417-22. DOI: 10.1016/s0168-9525(98)01555-8. View

Hu X, Yuan J, Shi Y, Lu J, Liu B, Li Z . pIRS: Profile-based Illumina pair-end reads simulator. Bioinformatics. 2012; 28(11):1533-5. DOI: 10.1093/bioinformatics/bts187. View

Ou Z, Stankiewicz P, Xia Z, Breman A, Dawson B, Wiszniewska J . Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes. Genome Res. 2011; 21(1):33-46. PMC: 3012924. DOI: 10.1101/gr.111609.110. View

10.

Abecasis G, Auton A, Brooks L, DePristo M, Durbin R, Handsaker R . An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491(7422):56-65. PMC: 3498066. DOI: 10.1038/nature11632. View

11.

Clarke J, Wu H, Jayasinghe L, Patel A, Reid S, Bayley H . Continuous base identification for single-molecule nanopore DNA sequencing. Nat Nanotechnol. 2009; 4(4):265-70. DOI: 10.1038/nnano.2009.12. View

12.

Smith A, Esko J, Hajduk S . Killing of trypanosomes by the human haptoglobin-related protein. Science. 1995; 268(5208):284-6. DOI: 10.1126/science.7716520. View

13.

Pevzner P, Pevzner P, Tang H, Tesler G . De novo repeat classification and fragment assembly. Genome Res. 2004; 14(9):1786-96. PMC: 515325. DOI: 10.1101/gr.2395204. View

14.

Datta A, Hendrix M, Lipsitch M . Dual roles for DNA sequence identity and the mismatch repair system in the regulation of mitotic crossing-over in yeast. Proc Natl Acad Sci U S A. 1997; 94(18):9757-62. PMC: 23263. DOI: 10.1073/pnas.94.18.9757. View

15.

Sun X, Zhang H, Wang D, Ma D, Shen Y, Shang Y . DLP, a novel Dim1 family protein implicated in pre-mRNA splicing and cell cycle progression. J Biol Chem. 2004; 279(31):32839-47. DOI: 10.1074/jbc.M402522200. View

16.

Lupski J . Hotspots of homologous recombination in the human genome: not all homologous sequences are equal. Genome Biol. 2004; 5(10):242. PMC: 545587. DOI: 10.1186/gb-2004-5-10-242. View

17.

Stankiewicz P, Lupski J . Structural variation in the human genome and its role in disease. Annu Rev Med. 2010; 61:437-55. DOI: 10.1146/annurev-med-100708-204735. View

18.

Huertas P . DNA resection in eukaryotes: deciding how to fix the break. Nat Struct Mol Biol. 2010; 17(1):11-6. PMC: 2850169. DOI: 10.1038/nsmb.1710. View

19.

Hastings P, Lupski J, Rosenberg S, Ira G . Mechanisms of change in gene copy number. Nat Rev Genet. 2009; 10(8):551-64. PMC: 2864001. DOI: 10.1038/nrg2593. View

20.

Zanger U, Schwab M . Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013; 138(1):103-41. DOI: 10.1016/j.pharmthera.2012.12.007. View