Complex Genetic Architecture Revealed by Analysis of HDL in Chromosome Substitution Strains and F2 Crosses
Ioannis M Stylianou 1, Shirng-Wern Tsaih 1, Keith DiPetrillo 1, Naoki Ishimori 1, Renhua Li 1, Beverly Paigen 1 and Gary A Churchill 1*
1 The Jackson Laboratory
* To whom correspondence should be addressed. E-mail: garyc{at}jax.org.
Submitted on April 19, 2006
Revised on June 8, 2006
Accepted on 3 August 2006
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Abstract |
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Intercrosses between inbred lines provide a traditional approach to analysis of polygenic inheritance in model organisms. Chromosome substitution strains (CSS) have been developed as an alternative to accelerate the pace of quantitative genetic analysis. 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 BxA 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 BxA intercross population. Intercrosses between B and three CSS (CSS-3, CSS-11 and CSS- 8) each revealed significant QTL but with some unexpected differences from the BxA intercross. Our inability to predict the results of CSS intercrosses suggests that additional complexity will be revealed by further crosses. Our empirical analysis of the efficiency of the CSS mapping strategy suggests that this approach should be viewed as complement to, rather than a replacement for, classical intercross mapping.
Key Words:
Epistasis, cholesterol, consomic, lipoproteins
