Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-6-20
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1531-2267
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-25
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17356016-Animals, pubmed-meshheading:17356016-Aorta, pubmed-meshheading:17356016-Aorta, Abdominal, pubmed-meshheading:17356016-Aorta, Thoracic, pubmed-meshheading:17356016-Chromosome Mapping, pubmed-meshheading:17356016-Chromosomes, Mammalian, pubmed-meshheading:17356016-Ductus Arteriosus, Patent, pubmed-meshheading:17356016-Elastin, pubmed-meshheading:17356016-Female, pubmed-meshheading:17356016-Gene Expression Profiling, pubmed-meshheading:17356016-Genetic Linkage, pubmed-meshheading:17356016-Genotype, pubmed-meshheading:17356016-Male, pubmed-meshheading:17356016-Myosins, pubmed-meshheading:17356016-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17356016-Phenotype, pubmed-meshheading:17356016-Polymorphism, Single Nucleotide, pubmed-meshheading:17356016-Quantitative Trait Loci, pubmed-meshheading:17356016-Rats, pubmed-meshheading:17356016-Rats, Inbred BN, pubmed-meshheading:17356016-Renal Artery
pubmed:year
2007
pubmed:articleTitle
Quantitative genetic basis of arterial phenotypes in the Brown Norway rat.
pubmed:affiliation
Max Delbrück Centrum for Molecular Medicine, Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't