Genome screen for bone mineral density phenotypes in Fisher 344 and Lewis rat strains

Koller, Daniel L.; Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Fishburn, Tonya; Carr, Lucinda G.; Econs, Michael J.; Foroud, Tatiana; Turner, Charles H.

doi:10.1007/s00335-004-2459-0

Cited by 25 publications

(47 citation statements)

References 20 publications

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“…The Lewis and Fischer inbred rat strains have been used as a model of human aging-related traits [10][11][12] including an intercross genome screening study of bone properties [13]. The power of the mouse as a genetic tool has been utilized to uncover genes whose normal allelic variation regulates BMD and other skeletal traits such as bone geometry, microarchitecture and strength [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

Sabsovich

Clark

Liao³

et al. 2008

Bone

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MicroCT analysis of 12 inbred strains of mice identified 5 novel chromosomal regions influencing skeletal phenotype. Bone morphology varied in a compartment-and site-specific fashion across strains and genetic influences contributed to the morphometric similarities observed in femoral and vertebral bone within the trabecular bone compartment.Introduction-Skeletal development is known to be regulated by both heritable and environmental factors, but whether genetic influence on peak bone mass is site-or compartment-specific is unknown. This study examined the genetic variation of cortical and trabecular bone microarchitecture across 12 strains of mice.

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Section: Introductionmentioning

confidence: 99%

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

Sabsovich

Clark

Liao³

et al. 2008

Bone

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“…(3) We previously reported results from a microsatellite genome screen for peak BMD phenotypes in the laboratory rat (Rattus norvegicus), using the inbred Lewis (LEW) and Fischer 344 (F344) strains to generate a population of F 2 females. (4) Highly significant quantitative trait loci (QTLs)…”

Section: Introductionmentioning

confidence: 99%

Linkage Screen for BMD Phenotypes in Male and Female COP and DA Rat Strains

Koller

Liu

Alam

et al. 2008

Journal of Bone and Mineral Research

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ABSTRACT:Because particular inbred strains of experimental animals are informative for only a subset of the genes underlying variability in BMD, we undertook a genome screen to identify quantitative trait loci (QTLs) in 828 F 2 progeny (405 males and 423 females) derived from the Copenhagen 2331 (COP) and dark agouti (DA) strains of rats. This screen was performed to complement our study in female Fischer 344 (F344) and Lewis (LEW) rats and to further delineate the factors underlying the complex genetic architecture of BMD in the rat model. Microsatellite genotyping was performed using markers at an average density of 20 cM. BMD was measured by pQCT and DXA. These data were analyzed in the R/qtl software to detect QTLs acting in both sexes as well as those having sex-specific effects. A QTL was detected in both sexes on chromosome 18 for midfemur volumetric BMD (vBMD; genome-wide, p < 0.01). On distal chromosome 1, a QTL was found for femur and vertebral aBMD as well as distal femur vBMD, and this QTL appears distinct from the proximal chromosome 1 QTL impacting BMD in our F344/LEW cross. Additional aBMD and vBMD QTLs and several sex-specific QTLs were also detected. These included a male-specific QTL (p < 0.01) on chromosome 8 and a female-specific QTL on chromosomes 7 and 14 (p < 0.01). Few of the QTLs identified showed overlap with the significant QTLs from the F344/LEW cross. These results confirm that the genetic influence on BMD in the rat model is quite complex and would seem to be influenced by a number of different genes, some of which have sex-specific effects.

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“…Linkage analysis has also been used to localize QTL for other osteoporosis-related phenotypes such as bone structure, bone shape and bone strength [16]. Loci for regulation of BMD have now been identified on almost all mouse chromosomes, and several rat chromosomes with replication of some QTL across different strains, and replication of some human BMD QTL [15]. These studies have also shown that the genes which regulate BMD in mice have effects that are site-specific and gender-specific [17].…”

Section: Animal Studiesmentioning

confidence: 99%

“…A genome wide search is then performed in the F2 generation and inheritance of alleles related to levels of BMD in the offspring. Linkage studies in mice, rats and primates have resulted in the identification of several quantitative trait loci (QTL) that regulate BMD [14,15]. Linkage analysis has also been used to localize QTL for other osteoporosis-related phenotypes such as bone structure, bone shape and bone strength [16].…”

Section: Animal Studiesmentioning

confidence: 99%

Osteoporosis as an Hereditary Disease

Ralston

2010

Clinic Rev Bone Miner Metab

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Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and increased risk of fragility fractures. Twin and family studies have shown that bone mineral density (BMD) and other determinants of fracture risk such as ultrasound properties of bone, skeletal geometry, and bone turnover have a significant heritable component. Osteoporotic fractures also have a genetic component but heritability reduces dramatically with increasing age. Many different genetic variants contribute to the regulation of these phenotypes; most are common variants of small effect size, but there is evidence that rare variants of large effect size also contribute in some individuals. Genome wide association studies have recently been successfully employed to identifying genes that predispose to osteoporosis, although some of these had already been identified through the study of rare bone diseases. Although there has been extensive progress in understanding the genetic basis of osteoporosis over the past 10 years, most of the genetic variants that regulate bone mass remained to be discovered.

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Genome screen for bone mineral density phenotypes in Fisher 344 and Lewis rat strains

Cited by 25 publications

References 20 publications

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

Linkage Screen for BMD Phenotypes in Male and Female COP and DA Rat Strains

Osteoporosis as an Hereditary Disease

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