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PMID: 19543269 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans.

Nature genetics ·Vol. 41 ·No. 7 ·2009-07-00 ·Pages 849-53

Zhang F, Khajavi M, Connolly AM, Towne CF, Batish SD, Lupski JR

Abstract

We recently proposed a DNA replication-based mechanism of fork stalling and template switching (FoSTeS) to explain the complex genomic rearrangements associated with a dysmyelinating central nervous system disorder in humans. The FoSTeS mechanism has been further generalized and molecular mechanistic details have been provided in the microhomology-mediated break-induced replication (MMBIR) model that may underlie many structural variations in genomes from all domains of life. Here we provide evidence that human genomic rearrangements ranging in size from several megabases to a few hundred base pairs can be generated by FoSTeS/MMBIR. Furthermore, we show that FoSTeS/MMBIR-mediated rearrangements can occur mitotically and can result in duplication or triplication of individual genes or even rearrangements of single exons. The FoSTeS/MMBIR mechanism can explain both the gene duplication-divergence hypothesis and exon shuffling, suggesting an important role in both genome and single-gene evolution.

MeSH Terms
Abnormalities, Multiple/genetics DNA Replication Evolution, Molecular Exons Gene Rearrangement Humans Myelin Proteins/genetics Syndrome
Chemicals
Myelin Proteins PMP22 protein, human
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zhang Feng
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Khajavi Mehrdad
Connolly Anne M
Towne Charles F
Batish Sat Dev
Lupski James R
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.399
Published
2009-07-00
Epub
2009-00-21
Pages
849-53
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC4461229
Subset
IM
Grants
NINDS NIH HHS · R01 NS058529 · United States
External Links
PubMed source DOI: 10.1038/ng.399 PMC Full Text View journal details
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