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Genetic Regulation of Bone Traits Is Influenced by Sex and Reciprocal Cross in F 2 Progeny From GK and F344 Rats
Author(s) -
Lagerholm Sofia,
Li LuoSheng,
Jiao Hong,
Park HeeBok,
Ohlsson Claes,
Åkesson Kristina,
Luthman Holger
Publication year - 2009
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.081252
Subject(s) - quantitative trait locus , biology , genetic linkage , reciprocal cross , phenotype , genetics , sex linkage , inbred strain , gene , chromosome , hybrid , botany
A genome‐wide linkage analysis to identify quantitative trait loci (QTLs) for bone phenotypes was performed in an F 2 intercross of inbred spontaneously type 2 diabetic GK and normoglycemic F344 rats (108 males and 98 females). The aim of the study was to locate genome regions with candidate genes affecting trabecular and cortical bone and to investigate the effects of sex and reciprocal cross. pQCT was used to determine tibial bone phenotypes in the F 2 rats, comprising reciprocal crosses with divergent mitochondrial (mt) DNA. Sex and reciprocal cross‐separated QTL analyses were performed followed by assessment of specific interactions. Four genome‐wide significant QTLs linked to either cortical vBMD, tibia length, body length, or metaphyseal area were identified in males on chromosomes (chr) 1, 8, and 15. In females, three significant QTLs linked to cortical BMC or metaphyseal total vBMD were identified on chr 1 and 2. Several additional suggestive loci for trabecular and cortical traits were detected in both males and females. Four female‐specific QTLs on chr 2, 3, 5, and 10 and four reciprocal cross‐specific QTLs on chr 1, 10, and 18 were identified, suggesting that both sex and mt genotype influence the expression of bone phenotypes.