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Quantitative genetic basis of arterial phenotypes in the Brown Norway rat

Item Type:Article
Title:Quantitative genetic basis of arterial phenotypes in the Brown Norway rat
Creators Name:Kota, L. and Osborne-Pellegrin, M. and Schulz, H. and Behmoaras, J. and Coutard, M. and Gong, M. and Huebner, N.
Abstract:The Brown Norway (BN) rat presents several genetically determined arterial phenotypes of pathophysiological and fundamental interest. These include ruptures of the internal elastic lamina (RIEL) in the abdominal aorta (AA), iliac (IAs) and renal arteries, an aortic elastin deficit and a higher frequency of persistent ductus arteriosus (PDA) than other rat strains. Here we investigate the genetic basis of these phenotypes. A backcross was established between BN and the LOU reference strain and a genome wide linkage analysis was performed. RIEL in AA and IAs showed highly significant linkage to a locus on chromosome 5 and suggestive linkage to a locus on chromosome 10, which is syntenic to one linked to a syndrome of thoracic aortic aneurysms with PDA in humans. In contrast, renal artery RIEL mapped to a locus on chromosome 3 and thoracic aortic elastic content to two loci on chromosome 2. PDA was significantly linked to two different QTL on chromosomes 8 and 9. This is the first study in rat to identify genetic loci for PDA. 21 candidate genes were identified by functional relevance or integration of our mapping data with global expression analysis. Sequencing these genes identified 47 SNPs, but no functionally relevant amino-acid changes. By expression analysis, Myosin heavy chain 10, non-muscle (Myh10), located in the chromosome 10 QTL, emerged as a candidate for RIEL in AA and IAs. Furthermore, production of a congenic line for the chromosome 5 QTL proved the implication of this locus in RIEL formation. These data provide a basis for further studies to elucidate the genes involved in the phenotypes concerned. Key words: Internal elastic lamina, abdominal aorta, elastin, ductus arteriosus, quantitative trait loci.
Keywords:Internal elastic lamina, Abdominal aorta, Elastin, Ductus arteriosus, Quantitative trait, Animals, Rats
Source:Physiological Genomics
ISSN:1094-8341
Publisher:American Physiological Society (U.S.A.)
Volume:30
Number:1
Page Range:17-25
Date:1 June 2007
Official Publication:https://doi.org/10.1152/physiolgenomics.00209.2006
PubMed:View item in PubMed

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