A recurrent translocation is mediated by homologous recombination between HERV-H elements
Karen E Hermetz1, Urvashi Surti, Jannine D Cody
1Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA. katie.rudd@emory.edu.
Molecular Cytogenetics
|January 21, 2012
Summary
Recurrent translocations between chromosomes 4 and 18 in children with intellectual disability were caused by recombination between human endogenous retroviruses (HERVs). This study reveals interchromosomal HERV-HERV recombination as a novel mechanism for chromosomal rearrangement.
Area of Science:
- Genetics
- Molecular Biology
- Human Disease
Background:
- Recurrent chromosome rearrangements offer insights into DNA sequence-specific mutation mechanisms.
- Homologous recombination between segmental duplications can mediate recurrent translocations.
- Intellectual disability can be associated with chromosomal abnormalities.
Purpose of the Study:
- To investigate the mechanism of a recurrent unbalanced translocation involving chromosomes 4 and 18 in two children with intellectual disability.
- To identify the DNA sequences mediating the observed translocation.
Main Methods:
- Array comparative genomic hybridization (CGH) to map translocation breakpoints.
- DNA sequencing to analyze the precise recombination sites.
- Analysis of human endogenous retroviruses (HERVs) at breakpoints.
Main Results:
- Characterized a 6.97-Mb deletion on chromosome 18 and a 7.30-Mb duplication on chromosome 4.
- Identified that translocations occurred between highly similar human endogenous retrovirus (HERV) elements on chromosomes 4 and 18.
- Discovered sequence variation in a chromosome 4 HERV element.
Conclusions:
- This is the first report of interchromosomal recombination between HERVs causing a translocation.
- Homologous recombination between HERVs can lead to chromosomal deletions and translocations.
- Sequence variation in non-allelic homologous recombination (NAHR) substrates may influence chromosome rearrangement susceptibility.
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