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.

Methods And 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.

A phenotype-sensitizing Apoe-deficient genetic background reveals novel atherosclerosis predisposition loci in the mouse.

Therapeutic intervention for atherosclerosis has predominantly concentrated on regulating cholesterol levels; however, these therapeutics are not efficacious for all patients, suggesting that other factors are involved. This study was initiated to identify mechanisms that regulate atherosclerosis predisposition in mice other than cholesterol level regulation. To do so we performed quantitative trait locus analysis using two inbred strains that each carry the atherosclerosis phenotype-sensitizing Apoe deficiency and that have been shown to have widely disparate predilection to atherosclerotic lesion formation.

Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10-15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction.