Quantitative Trait Locus Analysis of Susceptibility to Diet-induced Atherosclerosis in Recombinant Inbred Mice

Overview

Journal Biochem Genet

Specialty Molecular Biology

Date 1994 Dec 1

PMID 7748156

Citations 4

Authors

R W HYMAN

S Frank

C H Warden

A Daluiski

R Heller

A J Lusis

Affiliations

Soon will be listed here.

Abstract

Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumably Apoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus.

Citing Articles

Identification of Quantitative Trait Loci That Determine Plasma Total-Cholesterol and Triglyceride Concentrations in DDD/Sgn and C57BL/6J Inbred Mice.

Suto J, Kojima M Cholesterol. 2017; 2017:3178204.

PMID: 28642824 PMC: 5469984. DOI: 10.1155/2017/3178204.

Responsiveness of cardiometabolic-related microbiota to diet is influenced by host genetics.

OConnor A, Quizon P, Albright J, Lin F, Bennett B Mamm Genome. 2014; 25(11-12):583-99.

PMID: 25159725 PMC: 4239785. DOI: 10.1007/s00335-014-9540-0.

High-resolution association mapping of atherosclerosis loci in mice.

Bennett B, Orozco L, Kostem E, Erbilgin A, Dallinga M, Neuhaus I Arterioscler Thromb Vasc Biol. 2012; 32(8):1790-8.

PMID: 22723443 PMC: 3519423. DOI: 10.1161/ATVBAHA.112.253864.

Complex genetic control of HDL levels in mice in response to an atherogenic diet. Coordinate regulation of HDL levels and bile acid metabolism.

Machleder D, Ivandic B, Welch C, Castellani L, Reue K, Lusis A J Clin Invest. 1997; 99(6):1406-19.

PMID: 9077551 PMC: 507957. DOI: 10.1172/JCI119300.

References

Paigen B, Mitchell D, Reue K, Morrow A, Lusis A, LeBoeuf R . Ath-1, a gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice. Proc Natl Acad Sci U S A. 1987; 84(11):3763-7. PMC: 304956. DOI: 10.1073/pnas.84.11.3763. View

Qiao J, Welch C, Xie P, Fishbein M, Lusis A . Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development. J Clin Invest. 1993; 92(5):2386-93. PMC: 288421. DOI: 10.1172/JCI116844. View

Paigen B, Albee D, Holmes P, Mitchell D . Genetic analysis of murine strains C57BL/6J and C3H/HeJ to confirm the map position of Ath-1, a gene determining atherosclerosis susceptibility. Biochem Genet. 1987; 25(7-8):501-11. DOI: 10.1007/BF00554352. View

Paigen B, Morrow A, Brandon C, Mitchell D, Holmes P . Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis. 1985; 57(1):65-73. DOI: 10.1016/0021-9150(85)90138-8. View

Paigen B, Ishida B, Verstuyft J, Winters R, Albee D . Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice. Arteriosclerosis. 1990; 10(2):316-23. DOI: 10.1161/01.atv.10.2.316. View

Paigen B, Morrow A, Holmes P, Mitchell D, Williams R . Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis. 1987; 68(3):231-40. DOI: 10.1016/0021-9150(87)90202-4. View

Bachorik P, Albers J . Precipitation methods for quantification of lipoproteins. Methods Enzymol. 1986; 129:78-100. DOI: 10.1016/0076-6879(86)29063-1. View

Paterson A, Lander E, Hewitt J, Peterson S, Lincoln S, Tanksley S . Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms. Nature. 1988; 335(6192):721-6. DOI: 10.1038/335721a0. View

Lusis A, Taylor B, Wangenstein R, LeBoeuf R . Genetic control of lipid transport in mice. II. Genes controlling structure of high density lipoproteins. J Biol Chem. 1983; 258(8):5071-8. View

10.

LeBoeuf R, Doolittle M, Montcalm A, Martin D, Reue K, Lusis A . Phenotypic characterization of the Ath-1 gene controlling high density lipoprotein levels and susceptibility to atherosclerosis. J Lipid Res. 1990; 31(1):91-101. View

11.

LeBoeuf R, Puppione D, Schumaker V, Lusis A . Genetic control of lipid transport in mice. I. Structural properties and polymorphisms of plasma lipoproteins. J Biol Chem. 1983; 258(8):5063-70. View

12.

Lough J, Skamene E . ATH-3, a new gene for atherosclerosis in the mouse. Clin Invest Med. 1989; 12(2):121-6. View

13.

Breckenridge W, Roberts A, Kuksis A . Lipoprotein levels in genetically selected mice with increased susceptibility to atherosclerosis. Arteriosclerosis. 1985; 5(3):256-64. DOI: 10.1161/01.atv.5.3.256. View

14.

Qiao J, Castellani L, Fishbein M, Lusis A . Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice. Arterioscler Thromb. 1993; 13(6):932-43. DOI: 10.1161/01.atv.13.6.932. View

15.

Warnick G . Enzymatic methods for quantification of lipoprotein lipids. Methods Enzymol. 1986; 129:101-23. DOI: 10.1016/0076-6879(86)29064-3. View

16.

Manly K, Elliott R . RI Manager, a microcomputer program for analysis of data from recombinant inbred strains. Mamm Genome. 1991; 1(2):123-6. DOI: 10.1007/BF02443789. View