RGD Reference Report - Quantitative genetic basis of arterial phenotypes in the Brown Norway rat. - Rat Genome Database

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Quantitative genetic basis of arterial phenotypes in the Brown Norway rat.

Authors: Kota, L  Osborne-Pellegrin, M  Schulz, H  Behmoaras, J  Coutard, M  Gong, M  Hubner, N 
Citation: Kota L, etal., Physiol Genomics. 2007 Jun 19;30(1):17-25. Epub 2007 Mar 13.
RGD ID: 8662443
Pubmed: PMID:17356016   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00209.2006   (Journal Full-text)

The Brown Norway (BN) rat presents several genetically determined arterial phenotypes of interest, i.e., ruptures of the internal elastic lamina (RIEL) in the abdominal aorta (AA), iliac (IAs), and renal arteries, aortic elastin deficit and higher frequency of persistent ductus arteriosus (PDA) than other strains. We investigated the genetic basis of these phenotypes. We established a backcross between BN and the LOU reference strain and performed a genome-wide scan on 104 males and 105 females with 193 microsatellite markers followed by linkage analysis. 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 chromosome 3 locus and thoracic aortic elastic content to two loci on chromosome 2. PDA was significantly linked to two different quantitative trait loci (QTL) on chromosomes 8 and 9. This is the first study in rats to identify genetic loci for PDA. We identified 21 candidate genes by functional relevance or integration of our mapping data with global expression analysis. Sequencing these genes identified 47 single nucleotide polymorphisms, but no functionally relevant amino acid changes. By expression analysis, myosin heavy chain 10, nonmuscle, 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 implication of this locus in RIEL formation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
patent ductus arteriosus  IAGP 8662443; 8662443; 8662443 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal abdominal aorta morphology  IAGP 8662443compared to LOU/MBbbRGD 
abnormal aorta elastic tissue morphology  IDA 8662443; 8662443; 8662443; 8662443 RGD 
abnormal aorta elastin content  IDA 8662443 RGD 
abnormal renal artery morphology  IDA 8662443 RGD 
abnormal thoracic aorta morphology  IAGP 8662443compared to LOU/MBbbRGD 
aneurysm  IAGP 8662443compared to LOU/MBbbRGD 
aneurysm  IAGP 8662443compared to LOU/MBbb and BN/RjRGD 
decreased aorta elastin content  IAGP 8662443compared to LOU.MBbbRGD 
patent ductus arteriosus  IAGP 8662443compared to LOU/MBbbRGD 
patent ductus arteriosus  IDA 8662443; 8662443 RGD 

Objects Annotated

QTLs
Vetf10  (Vascular elastic tissue fragility QTL 10)
Vetf3  (Vascular elastic tissue fragility QTL 3)
Vetf4  (Vascular elastic tissue fragility QTL 4)
Vetf5  (Vascular elastic tissue fragility QTL 5)
Vetf6  (Vascular elastic tissue fragility QTL 6)
Vetf7  (Vascular elastic tissue fragility QTL 7)
Vetf8  (Vascular elastic tissue fragility QTL 8)
Vetf9  (Vascular elastic tissue fragility QTL 9)

Objects referenced in this article
QTL Vetf1 Vascular elastic tissue fragility QTL 1 Rattus norvegicus
QTL Vetf2 Vascular elastic tissue fragility QTL 2 Rattus norvegicus

Additional Information