title: Trps1 differentially modulates the bone mineral density between male and female mice and its polymorphism associates with BMD differently between women and men.
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.
authors.affiliation: Department of Orthopedic Surgery and BioMedical Engineering, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America ; Department of Basic Medicine, Inner Mongolia Medical University, Huhhot, Inner Mongolia, P.R. China.
authors.forename: Lishi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery and BioMedical Engineering, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Wenli
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery and BioMedical Engineering, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Orthopedic Surgery and BioMedical Engineering, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Scheib
authors.affiliation: Department of Orthopedic Surgery and BioMedical Engineering, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Myers
authors.affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Center for Public Health Genomics, Departments of Medicine (Division of Cardiology) and Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Farber
authors.affiliation: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Gaifen
authors.initials: G
authors.lastname: Liu
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China.
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.affiliation: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery and BioMedical Engineering, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Weikuan
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Orthopedic Surgery and BioMedical Engineering, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiao
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D050980:GATA Transcription Factors / Q000235:genetics*; D006801:Humans; D007178:Inbreeding; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics; D012097:Repressor Proteins; D012727:Sex Characteristics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050980:GATA Transcription Factors; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors; C525953:Trps1 protein, mouse