Trps1 differentially modulates the bone mineral density between male and female mice and its polymorphism associates with BMD differently between women and men.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 24416236.
- Also identified by DOI 10.1371/journal.pone.0084485 and PMC identifier 3885592.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Bone Density
- DNA-Binding Proteins
- GATA Transcription Factors
- Polymorphism, Single Nucleotide
- Sex Characteristics
- Transcription Factors