Faculty Collaboration Database

Complex genetic architecture revealed by analysis of high-density lipoprotein cholesterol in chromosome substitution strains and F2 crosses. Genetics 2006 Oct;174(2):999-1007

Date

09/05/2006

Pubmed ID

16951076

Pubmed Central ID

PMC1602087

DOI

10.1534/genetics.106.059717

Scopus ID

2-s2.0-33750478317 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

Intercrosses between inbred lines provide a traditional approach to analysis of polygenic inheritance in model organisms. Chromosome substitution strains (CSSs) have been developed as an alternative to accelerate the pace of gene identification in quantitative trait mapping. We compared a classical intercross and three CSS intercrosses to examine the genetic architecture underlying plasma high-density lipoprotein cholesterol (HDL) levels in the C57BL/6J (B) and A/J (A) mouse strains. The B x A intercross revealed significant quantitative trait loci (QTL) for HDL on chromosomes 1, 4, 8, 15, 17, 18, and 19. A CSS survey revealed that many have significantly different HDL levels compared to the background strain B, including chromosomes with no significant QTL in the intercross and, in some cases (CSS-1, CSS-17), effects that are opposite to those observed in the B x A intercross population. Intercrosses between B and three CSSs (CSS-3, CSS-11, and CSS-8) revealed significant QTL but with some unexpected differences from the B x A intercross. Our inability to predict the results of CSS intercrosses suggests that additional complexity will be revealed by further crosses and that the CSS mapping strategy should be viewed as a complement to, rather than a replacement for, classical intercross mapping.

Author List

Stylianou IM, Tsaih SW, DiPetrillo K, Ishimori N, Li R, Paigen B, Churchill G

Author

Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin

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

Animals
Cholesterol, HDL
Chromosomes, Mammalian
Crosses, Genetic
Female
Male
Mice
Mice, Inbred A
Mice, Inbred C57BL
Species Specificity