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

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Vetf5Ratpatent ductus arteriosus  IAGP  RGD 
Vetf6Ratpatent ductus arteriosus  IAGP  RGD 
Vetf7Ratpatent ductus arteriosus  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BN/RjRatabnormal abdominal aorta morphology  IAGP compared to LOU/MBbbRGD 
Vetf10Ratabnormal aorta elastic tissue morphology  IDA  RGD 
Vetf3Ratabnormal aorta elastic tissue morphology  IDA  RGD 
Vetf8Ratabnormal aorta elastic tissue morphology  IDA  RGD 
Vetf9Ratabnormal aorta elastic tissue morphology  IDA  RGD 
Vetf7Ratabnormal aorta elastin content  IDA  RGD 
Vetf4Ratabnormal renal artery morphology  IDA  RGD 
BN/RjRatabnormal thoracic aorta morphology  IAGP compared to LOU/MBbbRGD 
BN/RjRataneurysm  IAGP compared to LOU/MBbbRGD 
LOU.BN-(D5Rat59-D5Rat133)/BbbRataneurysm  IAGP compared to LOU/MBbb and BN/RjRGD 
BN/RjRatdecreased aorta elastin content  IAGP compared to LOU.MBbbRGD 
BN/RjRatpatent ductus arteriosus  IAGP compared to LOU/MBbbRGD 
Vetf5Ratpatent ductus arteriosus  IDA  RGD 
Vetf6Ratpatent ductus arteriosus  IDA  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