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Publication : Complex genetic architecture revealed by analysis of high-density lipoprotein cholesterol in chromosome substitution strains and F2 crosses.

First Author  Stylianou IM Year  2006
Journal  Genetics Volume  174
Issue  2 Pages  999-1007
PubMed ID  16951076 Mgi Jnum  J:114073
Mgi Id  MGI:3688109 Doi  10.1534/genetics.106.059717
Citation  Stylianou IM, et al. (2006) Complex genetic architecture revealed by analysis of high-density lipoprotein cholesterol in chromosome substitution strains and F2 crosses. Genetics 174(2):999-1007
abstractText  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.
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