Document Detail

How segmental duplications shape our genome: recent evolution of ABCC6 and PKD1 Mendelian disease genes.
MedLine Citation:
PMID:  18791038     Owner:  NLM     Status:  MEDLINE    
The completion of the Human Genome Project has brought the understanding that our genome contains an unexpectedly large proportion of segmental duplications. This poses the challenge of elucidating the consequences of recent duplications on physiology. We have conducted an in-depth study of a subset of segmental duplications on chromosome 16. We focused on PKD1 and ABCC6 duplications because mutations affecting these genes are responsible for the Mendelian disorders autosomal dominant polycystic kidney disease and pseudoxanthoma elasticum, respectively. We establish that duplications of PKD1 and ABCC6 are associated to low-copy repeat 16a and show that such duplications have occurred several times independently in different primate species. We demonstrate that partial duplication of PKD1 and ABCC6 has numerous consequences: the pseudogenes give rise to new transcripts and mediate gene conversion, which not only results in disease-causing mutations but also serves as a reservoir for sequence variation. The duplicated segments are also involved in submicroscopic and microscopic genomic rearrangements, contributing to structural variation in human and chromosomal break points in the gibbon. In conclusion, our data shed light on the recent and ongoing evolution of chromosome 16 mediated by segmental duplication and deepen our understanding of the history of two Mendelian disorder genes.
Orsolya Symmons; András Váradi; Tamás Arányi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-12
Journal Detail:
Title:  Molecular biology and evolution     Volume:  25     ISSN:  1537-1719     ISO Abbreviation:  Mol. Biol. Evol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-17     Completed Date:  2008-12-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8501455     Medline TA:  Mol Biol Evol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2601-13     Citation Subset:  IM    
Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary.
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MeSH Terms
Chromosomes, Human, Pair 16 / genetics
Gene Duplication*
Genome, Human
Multidrug Resistance-Associated Proteins / genetics*
Polycystic Kidney Diseases / genetics
Primates / genetics*
Pseudoxanthoma Elasticum / genetics
TRPP Cation Channels / genetics*
Reg. No./Substance:
0/ABCC6 protein, human; 0/Multidrug Resistance-Associated Proteins; 0/TRPP Cation Channels; 0/polycystic kidney disease 1 protein

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