Skip Navigation


MBE Advance Access originally published online on September 12, 2008
Molecular Biology and Evolution 2008 25(12):2601-2613; doi:10.1093/molbev/msn202
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
25/12/2601    most recent
msn202v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Symmons, O.
Right arrow Articles by Arányi, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Symmons, O.
Right arrow Articles by Arányi, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

How Segmental Duplications Shape Our Genome: Recent Evolution of ABCC6 and PKD1 Mendelian Disease Genes

Orsolya Symmons, András Váradi and Tamás Arányi

Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary

E-mail: aranyi{at}enzim.hu.

Accepted for publication September 8, 2008.

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.

Key Words: primate evolution • nonallelic homologous recombination • morpheus • segmental duplication • copy number variation • Mendelian disease genes

Hervé Philippe, Associate Editor


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.