Faculty Collaboration Database

Identification of two susceptibility loci for vascular fragility in the Brown Norway rat. Physiol Genomics 2001 Aug 28;6(3):183-9

Date

08/30/2001

Pubmed ID

11526202

DOI

10.1152/physiolgenomics.2001.6.3.183

Scopus ID

2-s2.0-0345820045 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

A trait of vascular fragility, characterized by the formation of abrupt defects within the elastic laminae of the abdominal aorta, has been identified in Brown Norway (BN) rats. These lesions are greatly exacerbated in F(1) rats from a BN x New Zealand genetically hypertensive (GH) intercross, implying that the genetic background provided by the GH rat influences lesion severity. The F(2) progeny of the BN x GH intercross were used to identify susceptibility loci for the lesions as well as exacerbating loci. Two major quantitative trait loci (QTLs) for number of internal elastic lamina lesions were identified on rat chromosomes 5 and 10, with the maximum "log of the odds ratio" (LOD) scores at D5Rat119 (LOD 5.0) and at D10Mit2 (LOD 4.5), respectively, together contributing 33.5% to the genetic variance. Further analysis revealed that the chromosome 10 locus exhibits a dominant mode of inheritance, with BN alleles being associated with increased lesion number (P < 0.0002) compared with GH homozygotes. This locus was in epistasis to a modifier locus on rat chromosome 2 at D2Mit14 (LOD score 2.12). A second major locus was identified on chromosome 5, exhibiting a semidominant mode of inheritance, again with the BN allele being significantly associated with increased lesion number (P < 0.0001). Furthermore, a locus influencing lesion severity was identified on chromosome 3 wherein GH alleles associated with increased severity. This is the first study to identify susceptibility loci for vascular elastic tissue fragility.

Author List

Harris EL, Stoll M, Jones GT, Granados MA, Porteous WK, Van Rij AM, Jacob HJ

MESH terms used to index this publication - Major topics in bold

Animals
Aorta, Abdominal
Chromosome Mapping
Crosses, Genetic
Female
Genetic Linkage
Genetic Markers
Genetic Predisposition to Disease
Genotype
Lod Score
Male
Phenotype
Quantitative Trait, Heritable
Rats
Rats, Inbred BN
Rats, Inbred SHR
Vascular Diseases