In silico quantitative trait locus map for atherosclerosis susceptibility in apolipoprotein E-deficient mice.
OBJECTIVE
Atherosclerosis susceptibility is a genetic trait that varies between mouse strains. The goal of this study was to use a public mouse single nucleotide polymorphism (SNP) database to define the genetic loci that are associated with this trait, without the need to perform strain intercrosses that are normally required to obtain these loci.


RESULTS
Apolipoprotein E (apoE)-deficient mice on 6 inbred genetic backgrounds were compared for atherosclerosis lesion size in the aortic root in 2 independent studies. After normalization to the C57BL/6 strain that was used in both studies, lesion areas were found in the following rank order: DBA/2J>C57BL/6>129/SV-ter>AKR/J approximately BALB/cByJ approximately C3H/HeJ. The log lesion difference in phenotypes between each of the 15 heterologous strain pairs was determined. A mouse SNP database was then used to calculate the genetic differences between the 15 strain pairs in partially overlapping 30-cM bins across the mouse genome. Correlation analyses were preformed to analyze the genetic and phenotypic differences among the strain pairs for each genetic region. The genetic regions with the highest correlations define the in silico quantitative trait loci (QTL) associated with the atherosclerosis phenotype. Five in silico atherosclerosis QTL were identified on chromosomes 1, 10, 14, 15, and 18. The loci on chromosomes 1, 10, 14, and 18 overlap with suggestive atherosclerosis QTL identified through analyses of an F(2) cohort derived from apoE-deficient mice on the C57BL/6 and FVB/N strains.


CONCLUSIONS
The 5 identified in silico QTL are candidates for further study to confirm the presence and identity of atherosclerosis susceptibility genes within these loci.
Smith
Jonathan D
JD
Rockefeller University, New York, NY, USA. smithj@lerner.ccf.org
James
Daylon
D
Dansky
Hayes M
HM
Wittkowski
Knut M
KM
Moore
Karen J
KJ
Breslow
Jan L
JL
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D001161:Arteriosclerosis / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D003433:Crosses, Genetic; D030541:Databases, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*
D001057:Apolipoproteins E