Trps1 differentially modulates the bone mineral density between male and female mice and its polymorphism associates with BMD differently between women and men

Lishi Wang, Wenli Lu, Lei Zhang, Yue Huang, Rachel Scheib, Xiaoyun Liu, Linda Myers, Lu Lu, Charles R. Farber, Gaifen Liu, Cong Yi Wang, Hongwen Deng, Robert Williams, Yongjun Wang, Weikuan Gu, Yan Jiao

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Abstract

The objective of our study was to identify genetic factors that regulate bone mineral density (BMD) in mice using well defined recombinant inbred strains. For this purpose we chose the BXD recombinant inbred (RI) strains derived from progeny of the C57BL/6J (B6) and DBA/2J (D2) progenitor strains. We sampled both male and female mice (∼4 each) of 46 strains at 3 months-of-age, measured their BMD, and conducted QTL mapping. The data were analyzed to identify candidates genes contained within the most significant quantitative trait locus (QTL). Evaluation of candidate genes included functional assessment, single nucleotide polymorphism (SNP) genotyping and direct sequencing. We established that there was a QTL for BMD in males on chromosome 15 that has the impact larger than QTLs on all other chromosomes. The QTL on chromosome 15 was narrowed to a genomic region between 38 Mbp and 52 Mbp. By examining transcripts within this region, we found an important candidate gene: trichorhinophalangeal syndrome, type I (Trps1). SNP analysis identified a nonsynonymous SNP (rs32398060) in Trps1 that co-segregated with bone mineral density. Analysis of association between this SNP within TRPS1 and BMD in a human population confirmed its significance.

Original languageEnglish (US)
Article numbere84485
JournalPLoS ONE
Volume9
Issue number1
DOIs
StatePublished - Jan 8 2014

Fingerprint

bone density
Polymorphism
Bone Density
Quantitative Trait Loci
Minerals
quantitative trait loci
Bone
single nucleotide polymorphism
genetic polymorphism
Single Nucleotide Polymorphism
Nucleotides
Chromosomes
mice
Chromosomes, Human, Pair 15
Genes
chromosomes
Functional assessment
genes
human population
genotyping

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Trps1 differentially modulates the bone mineral density between male and female mice and its polymorphism associates with BMD differently between women and men. / Wang, Lishi; Lu, Wenli; Zhang, Lei; Huang, Yue; Scheib, Rachel; Liu, Xiaoyun; Myers, Linda; Lu, Lu; Farber, Charles R.; Liu, Gaifen; Wang, Cong Yi; Deng, Hongwen; Williams, Robert; Wang, Yongjun; Gu, Weikuan; Jiao, Yan.

In: PLoS ONE, Vol. 9, No. 1, e84485, 08.01.2014.

Research output: Contribution to journalArticle

Wang, Lishi ; Lu, Wenli ; Zhang, Lei ; Huang, Yue ; Scheib, Rachel ; Liu, Xiaoyun ; Myers, Linda ; Lu, Lu ; Farber, Charles R. ; Liu, Gaifen ; Wang, Cong Yi ; Deng, Hongwen ; Williams, Robert ; Wang, Yongjun ; Gu, Weikuan ; Jiao, Yan. / Trps1 differentially modulates the bone mineral density between male and female mice and its polymorphism associates with BMD differently between women and men. In: PLoS ONE. 2014 ; Vol. 9, No. 1.
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