Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations

被引：81

作者：

Robberecht, Caroline ^{[1
]}

Voet, Thierry ^{[2
]}

Esteki, Masoud Zamani ^{[2
]}

Nowakowska, Beata A. ^{[1
]}

Vermeesch, Joris R. ^{[1
]}

机构：

[1] Katholieke Univ Leuven, Dept Human Genet, Lab Mol Cytogenet & Genome Res, B-3000 Louvain, Belgium

[2] Katholieke Univ Leuven, Dept Human Genet, Lab Reprod Genom, B-3000 Louvain, Belgium

来源：

GENOME RESEARCH | 2013年 / 23卷 / 03期

关键词：

DOUBLE-STRAND BREAKS; AT-RICH PALINDROMES; BALANCED TRANSLOCATIONS; LINE-1; ELEMENTS; CHROMOSOMES; 4Q; REARRANGEMENTS; GENE; MECHANISMS; REPAIR; DUPLICATIONS;

D O I：

10.1101/gr.145631.112

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Large-scale analysis of balanced chromosomal translocation breakpoints has shown nonhomologous end joining and microhomology-mediated repair to be the main drivers of interchromosomal structural aberrations. Breakpoint sequences of de novo unbalanced translocations have not yet been investigated systematically. We analyzed 12 de novo unbalanced translocations and mapped the breakpoints in nine. Surprisingly, in contrast to balanced translocations, we identify nonallelic homologous recombination (NAHR) between (retro) transposable elements and especially long interspersed elements (LINEs) as the main mutational mechanism. This finding shows yet another involvement of (retro)transposons in genomic rearrangements and exposes a profoundly different mutational mechanism compared with balanced chromosomal translocations. Furthermore, we show the existence of compound maternal/paternal derivative chromosomes, reinforcing the hypothesis that human cleavage stage embryogenesis is a cradle of chromosomal rearrangements.

引用

页码：411 / 418

页数：8

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