Localization Of Qtls Regulating The Onset Of Puberty By Whole Genome Scanning In Mice

Puberty, often influenced by both environmental and genetic factors, is a complicated biologic process involving sexual maturation and gaining ability of reproduction. In order to find the QTLs regulating the onset of puberty, two inbred strains of mice C3H/HeJ and C57BL/6J were selected and two kinds of F2 pedigrees were founded by hybridization of the two strains in reciprocal crosses. Balano-preputial separation (BPS) was used to characterize the pubertal onset of male mice and vaginal opening (VO) was used to characterize the pubertal onset of the female. And the age at pubertal onset of all these mice (parent, F1 and F2) were recorded. And the phenotype of pubertal timing of all the mice (parent, F1 and F2) were recorded. The variance for pubertal timing between progenitor strains, F1 and F2 progeny were analyzed. Phenotypic data showed that in female mice, significant difference of this trait was observed between B6 and C3H(P=3.7×10^-13 ) as well as between direct and reciprocal F1 hybrids (P=5.4×10^-3), but not between direct and reciprocal F2 hybrids (P=0.0941). And in female mice, the heritability of the timing of puberty in direct and reciprocal crosses is 63.97% and 68.48%, respectively. The result demonstrated that we had set up two successful pedigrees. 259 phenotypically extreme F2 female mice with 6-10 pup per litter from 534 female F2 progeny were selected and chromosome-wide screen was carried out on whole genome. 86 STR and SNP markers were chosen with an average intermarker distance of about 15 to 20cM for the positional cloning of QTLs regulating the onset of puberty.Previous studies of our research group located three QTLs through chromosomal scanning on candidate chromosomes 6,13 and X. In the direct cross population (C3B6F2), one chromosomal region was found to contain a related quantitative trait locus (QTL) through linkage analysis. The region was found on chromosome X which was empirically significant (DXMit166, 15.5cM, LOD=3.856, p<0.05).This study was to identify whether other chromosomes harbor QTLs regulating the pubertal onset. Analysis based on the principle of linkage disequilibrium and linkage analysis was used on the genotyping data and age at VO was considered as quality and quantity trait respectively in linkage disequilibrium analysis. The result of linkage analysis showed that in the direct cross population, two suggestive QTL were detected on chromosome 5 and chromosome 12 respectively (D5Mit367, LOD=2.423; D12Mit144, LOD=2.196). And in reciprocal cross population, no significant QTL was found. We also used analysis of linkage disequilibrium to testify these two QTLs, p<0.05.Such findings in the study lay a foundation for positional cloning of genes regulating the timing of puberty.