Genetic dissection of femur breaking strength in a large population (MRL/MpJ x SJL/J) of F2 mice: Single QTL effects, epistasis, and pleiotropy

Xinmin Li, Godfred Masinde, Weikuan Gu, Jon Wergedal, Subburaman Mohan, David J. Baylink

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Bone breaking strength is an ultimate measurement of the risk of fracture. For a practical reason, bone mineral density (BMD) has been commonly used for predicting the risk instead. To identify genetic loci influencing femur-breaking strength (FBS), which was measured by three-point bending using an Instron DynaMight Low-Force Testing System, the whole-genome scan was carried out using 119 polymorphic markers in 633 (MRL x SJL) F2 female mice. We identified six significant quantitative trait loci (QTL) affecting bone breaking strength on chromosomes 1, 2, 8, 9, 10, and 17, which together explained 23% of F2 variance. Of those, the QTL on chromosomes 2, 8, and 10 seem to be unique to bone breaking strength, whereas the remaining three QTL are concordant with femur BMD QTL. Genetic analysis suggests that, of these six FBS QTL, three influence BMD, two influence bone quality, and one influences bone size. We detected multiple significant epistatic interactions for FBS, which accounts for half (14.6%) of F2 variance compared with significant single QTL effects. We found evidence that pleiotropic effect might represent a common genetic mechanism to coordinately regulate bone-related phenotypes. Pleiotropic analysis also suggests that our current threshold level for significant QTL may be too high to detect biologically significant QTL with small effect. Together with epistatic interactions, these undetected small QTL could explain 30% of genetic variance that remains unaccounted for in this study (heritability estimate for FBS is 68%). Our findings in single QTL effects, epistasis, and pleiotropy demonstrate that partially overlapped but distinct combinations of genetic loci in MRL/MpJ and SJL/J inbred strains of mice regulate bone strength and bone density. Identification of the genes unique to FBS may have an impact on prediction of osteoporosis in human.

Original languageEnglish (US)
Pages (from-to)734-740
Number of pages7
JournalGenomics
Volume79
Issue number5
DOIs
StatePublished - Jan 1 2002

Fingerprint

Quantitative Trait Loci
Femur
Dissection
Population
Bone and Bones
Bone Density
Genetic Loci
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 10
Inbred Strains Mice
Chromosomes, Human, Pair 1
Osteoporosis
Genome
Phenotype

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Genetic dissection of femur breaking strength in a large population (MRL/MpJ x SJL/J) of F2 mice : Single QTL effects, epistasis, and pleiotropy. / Li, Xinmin; Masinde, Godfred; Gu, Weikuan; Wergedal, Jon; Mohan, Subburaman; Baylink, David J.

In: Genomics, Vol. 79, No. 5, 01.01.2002, p. 734-740.

Research output: Contribution to journalArticle

Li, Xinmin ; Masinde, Godfred ; Gu, Weikuan ; Wergedal, Jon ; Mohan, Subburaman ; Baylink, David J. / Genetic dissection of femur breaking strength in a large population (MRL/MpJ x SJL/J) of F2 mice : Single QTL effects, epistasis, and pleiotropy. In: Genomics. 2002 ; Vol. 79, No. 5. pp. 734-740.
@article{0782b2e866c44e18b8b5c6a4e63abd78,
title = "Genetic dissection of femur breaking strength in a large population (MRL/MpJ x SJL/J) of F2 mice: Single QTL effects, epistasis, and pleiotropy",
abstract = "Bone breaking strength is an ultimate measurement of the risk of fracture. For a practical reason, bone mineral density (BMD) has been commonly used for predicting the risk instead. To identify genetic loci influencing femur-breaking strength (FBS), which was measured by three-point bending using an Instron DynaMight Low-Force Testing System, the whole-genome scan was carried out using 119 polymorphic markers in 633 (MRL x SJL) F2 female mice. We identified six significant quantitative trait loci (QTL) affecting bone breaking strength on chromosomes 1, 2, 8, 9, 10, and 17, which together explained 23{\%} of F2 variance. Of those, the QTL on chromosomes 2, 8, and 10 seem to be unique to bone breaking strength, whereas the remaining three QTL are concordant with femur BMD QTL. Genetic analysis suggests that, of these six FBS QTL, three influence BMD, two influence bone quality, and one influences bone size. We detected multiple significant epistatic interactions for FBS, which accounts for half (14.6{\%}) of F2 variance compared with significant single QTL effects. We found evidence that pleiotropic effect might represent a common genetic mechanism to coordinately regulate bone-related phenotypes. Pleiotropic analysis also suggests that our current threshold level for significant QTL may be too high to detect biologically significant QTL with small effect. Together with epistatic interactions, these undetected small QTL could explain 30{\%} of genetic variance that remains unaccounted for in this study (heritability estimate for FBS is 68{\%}). Our findings in single QTL effects, epistasis, and pleiotropy demonstrate that partially overlapped but distinct combinations of genetic loci in MRL/MpJ and SJL/J inbred strains of mice regulate bone strength and bone density. Identification of the genes unique to FBS may have an impact on prediction of osteoporosis in human.",
author = "Xinmin Li and Godfred Masinde and Weikuan Gu and Jon Wergedal and Subburaman Mohan and Baylink, {David J.}",
year = "2002",
month = "1",
day = "1",
doi = "10.1006/geno.2002.6760",
language = "English (US)",
volume = "79",
pages = "734--740",
journal = "Genomics",
issn = "0888-7543",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - Genetic dissection of femur breaking strength in a large population (MRL/MpJ x SJL/J) of F2 mice

T2 - Single QTL effects, epistasis, and pleiotropy

AU - Li, Xinmin

AU - Masinde, Godfred

AU - Gu, Weikuan

AU - Wergedal, Jon

AU - Mohan, Subburaman

AU - Baylink, David J.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - Bone breaking strength is an ultimate measurement of the risk of fracture. For a practical reason, bone mineral density (BMD) has been commonly used for predicting the risk instead. To identify genetic loci influencing femur-breaking strength (FBS), which was measured by three-point bending using an Instron DynaMight Low-Force Testing System, the whole-genome scan was carried out using 119 polymorphic markers in 633 (MRL x SJL) F2 female mice. We identified six significant quantitative trait loci (QTL) affecting bone breaking strength on chromosomes 1, 2, 8, 9, 10, and 17, which together explained 23% of F2 variance. Of those, the QTL on chromosomes 2, 8, and 10 seem to be unique to bone breaking strength, whereas the remaining three QTL are concordant with femur BMD QTL. Genetic analysis suggests that, of these six FBS QTL, three influence BMD, two influence bone quality, and one influences bone size. We detected multiple significant epistatic interactions for FBS, which accounts for half (14.6%) of F2 variance compared with significant single QTL effects. We found evidence that pleiotropic effect might represent a common genetic mechanism to coordinately regulate bone-related phenotypes. Pleiotropic analysis also suggests that our current threshold level for significant QTL may be too high to detect biologically significant QTL with small effect. Together with epistatic interactions, these undetected small QTL could explain 30% of genetic variance that remains unaccounted for in this study (heritability estimate for FBS is 68%). Our findings in single QTL effects, epistasis, and pleiotropy demonstrate that partially overlapped but distinct combinations of genetic loci in MRL/MpJ and SJL/J inbred strains of mice regulate bone strength and bone density. Identification of the genes unique to FBS may have an impact on prediction of osteoporosis in human.

AB - Bone breaking strength is an ultimate measurement of the risk of fracture. For a practical reason, bone mineral density (BMD) has been commonly used for predicting the risk instead. To identify genetic loci influencing femur-breaking strength (FBS), which was measured by three-point bending using an Instron DynaMight Low-Force Testing System, the whole-genome scan was carried out using 119 polymorphic markers in 633 (MRL x SJL) F2 female mice. We identified six significant quantitative trait loci (QTL) affecting bone breaking strength on chromosomes 1, 2, 8, 9, 10, and 17, which together explained 23% of F2 variance. Of those, the QTL on chromosomes 2, 8, and 10 seem to be unique to bone breaking strength, whereas the remaining three QTL are concordant with femur BMD QTL. Genetic analysis suggests that, of these six FBS QTL, three influence BMD, two influence bone quality, and one influences bone size. We detected multiple significant epistatic interactions for FBS, which accounts for half (14.6%) of F2 variance compared with significant single QTL effects. We found evidence that pleiotropic effect might represent a common genetic mechanism to coordinately regulate bone-related phenotypes. Pleiotropic analysis also suggests that our current threshold level for significant QTL may be too high to detect biologically significant QTL with small effect. Together with epistatic interactions, these undetected small QTL could explain 30% of genetic variance that remains unaccounted for in this study (heritability estimate for FBS is 68%). Our findings in single QTL effects, epistasis, and pleiotropy demonstrate that partially overlapped but distinct combinations of genetic loci in MRL/MpJ and SJL/J inbred strains of mice regulate bone strength and bone density. Identification of the genes unique to FBS may have an impact on prediction of osteoporosis in human.

UR - http://www.scopus.com/inward/record.url?scp=0036252133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036252133&partnerID=8YFLogxK

U2 - 10.1006/geno.2002.6760

DO - 10.1006/geno.2002.6760

M3 - Article

C2 - 11991724

AN - SCOPUS:0036252133

VL - 79

SP - 734

EP - 740

JO - Genomics

JF - Genomics

SN - 0888-7543

IS - 5

ER -