A dominant X-linked QTL regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis.
<h4>Background</h4>Pubertal timing in mammals is triggered by reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and environmental factors. Strain-dependent differences in vaginal opening among inbred mouse strains suggest that genetic background...
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2008
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oai:doaj.org-article:cf4d1c68401e4b8ca00d2d80be6ac20a2021-11-25T06:18:53ZA dominant X-linked QTL regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis.1932-620310.1371/journal.pone.0003021https://doaj.org/article/cf4d1c68401e4b8ca00d2d80be6ac20a2008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18725948/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Pubertal timing in mammals is triggered by reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and environmental factors. Strain-dependent differences in vaginal opening among inbred mouse strains suggest that genetic background contribute significantly to the puberty timing, although the exact mechanism remains unknown.<h4>Methodology/principal findings</h4>We performed a genome-wide scanning for linkage in reciprocal crosses between two strains, C3H/HeJ (C3H) and C57BL6/J (B6), which differed significantly in the pubertal timing. Vaginal opening (VO) was used to characterize pubertal timing in female mice, and the age at VO of all female mice (two parental strains, F1 and F2 progeny) was recorded. A genome-wide search was performed in 260 phenotypically extreme F2 mice out of 464 female progeny of the F1 intercrosses to identify quantitative trait loci (QTLs) controlling this trait. A QTL significantly associated was mapped to the DXMit166 marker (15.5 cM, LOD = 3.86, p<0.01) in the reciprocal cross population (C3HB6F2). This QTL contributed 2.1 days to the timing of VO, which accounted for 32.31% of the difference between the original strains. Further study showed that the QTL was B6-dominant and explained 10.5% of variation to this trait with a power of 99.4% at an alpha level of 0.05.The location of the significant ChrX QTL found by genome scanning was then fine-mapped to a region of approximately 2.5 cM between marker DXMit68 and rs29053133 by generating and phenotyping a panel of 10 modified interval-specific congenic strains (mISCSs).<h4>Conclusions/significance</h4>Such findings in our study lay a foundation for positional cloning of genes regulating the timing of puberty, and also reveal the fact that chromosome X (the sex chromosome) does carry gene(s) which take part in the regulative pathway of the pubertal timing in mice.Wangsheng ZhuZhongpeng FanChao ZhangZhengxia GuoYing ZhaoYuxun ZhouKai LiZhenghong XingGuoqiang ChenYinming LiangLi JinJunhua XiaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e3021 (2008) |
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Medicine R Science Q Wangsheng Zhu Zhongpeng Fan Chao Zhang Zhengxia Guo Ying Zhao Yuxun Zhou Kai Li Zhenghong Xing Guoqiang Chen Yinming Liang Li Jin Junhua Xiao A dominant X-linked QTL regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis. |
| description |
<h4>Background</h4>Pubertal timing in mammals is triggered by reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and environmental factors. Strain-dependent differences in vaginal opening among inbred mouse strains suggest that genetic background contribute significantly to the puberty timing, although the exact mechanism remains unknown.<h4>Methodology/principal findings</h4>We performed a genome-wide scanning for linkage in reciprocal crosses between two strains, C3H/HeJ (C3H) and C57BL6/J (B6), which differed significantly in the pubertal timing. Vaginal opening (VO) was used to characterize pubertal timing in female mice, and the age at VO of all female mice (two parental strains, F1 and F2 progeny) was recorded. A genome-wide search was performed in 260 phenotypically extreme F2 mice out of 464 female progeny of the F1 intercrosses to identify quantitative trait loci (QTLs) controlling this trait. A QTL significantly associated was mapped to the DXMit166 marker (15.5 cM, LOD = 3.86, p<0.01) in the reciprocal cross population (C3HB6F2). This QTL contributed 2.1 days to the timing of VO, which accounted for 32.31% of the difference between the original strains. Further study showed that the QTL was B6-dominant and explained 10.5% of variation to this trait with a power of 99.4% at an alpha level of 0.05.The location of the significant ChrX QTL found by genome scanning was then fine-mapped to a region of approximately 2.5 cM between marker DXMit68 and rs29053133 by generating and phenotyping a panel of 10 modified interval-specific congenic strains (mISCSs).<h4>Conclusions/significance</h4>Such findings in our study lay a foundation for positional cloning of genes regulating the timing of puberty, and also reveal the fact that chromosome X (the sex chromosome) does carry gene(s) which take part in the regulative pathway of the pubertal timing in mice. |
| format |
article |
| author |
Wangsheng Zhu Zhongpeng Fan Chao Zhang Zhengxia Guo Ying Zhao Yuxun Zhou Kai Li Zhenghong Xing Guoqiang Chen Yinming Liang Li Jin Junhua Xiao |
| author_facet |
Wangsheng Zhu Zhongpeng Fan Chao Zhang Zhengxia Guo Ying Zhao Yuxun Zhou Kai Li Zhenghong Xing Guoqiang Chen Yinming Liang Li Jin Junhua Xiao |
| author_sort |
Wangsheng Zhu |
| title |
A dominant X-linked QTL regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis. |
| title_short |
A dominant X-linked QTL regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis. |
| title_full |
A dominant X-linked QTL regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis. |
| title_fullStr |
A dominant X-linked QTL regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis. |
| title_full_unstemmed |
A dominant X-linked QTL regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis. |
| title_sort |
dominant x-linked qtl regulating pubertal timing in mice found by whole genome scanning and modified interval-specific congenic strain analysis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2008 |
| url |
https://doaj.org/article/cf4d1c68401e4b8ca00d2d80be6ac20a |
| work_keys_str_mv |
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| _version_ |
1718413954064056320 |