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Biomedical subjects

Robert R Recker

Publications and source records attributed to Robert R Recker.

79 records · Page 5Linked to original sources
PubMed2002

Role of genetics in osteoporosis.

Osteoporosis is a disease characterized by fragile bones and high susceptibility to low-trauma fractures. It is a serious health problem, especially in elderly women. Bone mineral density (BMD) has been employed most commonly as the index for defining and studying osteoporosis. BMD has high genetic determination, with heritability ranging from 50 to 90%. Various gene-mapping approaches have been applied to identify specific genes underlying osteoporosis, largely using BMD as the study phenotype. We review here the genetic determination of osteoporosis as defined by BMD and discuss a fundamental issue we encounter in genetic research in osteoporosis: the choice of phenotype(s) to study. We briefly summarize and discuss advantages and disadvantages of various approaches used in genetic studies of osteoporosis. Finally, we review and discuss the current status for mapping and identification of genes for osteoporosis. We focus on linkage studies in humans and quantitative trait loci mapping in mice to supplement the already extensive reviews of association studies made by many investigators for candidate genes.

Animals↗
PubMed2002

Determination of bone size of hip, spine, and wrist in human pedigrees by genetic and lifestyle factors.

Osteoporosis is a major public health problem defined as a loss of bone strength, of which bone size is an important determinant. Compared with extensive studies on bone mass, studies on the importance of factors determining variation in bone size are relatively few. In particular, the significance of genetic factors is largely unknown. In 49 pedigrees with 703 subjects bone sizes of the hip, spine, and wrist were measured by dual X-ray absorptiometry. We evaluated the contribution of genetic factors in determining variation in bone size of the hip, spine, and wrist while studying age, sex, weight, height, exercise, smoking, alcohol consumption, and the interaction among these factors as covariates for their effects on bone size. We found that, on average, males have larger bone sizes. Male bone sizes at the spine and hip increased with age; however, the effect of age in our female subjects was nonsignificant. Height invariably affected bone size at all the sites studied. Alcohol consumption and exercise generally had significant effects in increasing bone size at the spine and/or hip in both males and females. After adjusting for sex, age, weight, height, lifestyle factors, and the significant interactions among these factors, heritabilities (+/-SE) were, respectively, 0.48 (0.09), 0.64 (0.08), and 0.60 (0.09) for bone size at the hip, spine, and wrist.

Adult↗
PubMed2002

Fine mapping of susceptibility genes by Lewontin's linkage disequilibrium measure with application to Alzheimer's disease.

OBJECTIVES: To formulate an equation for fine mapping of disease loci under complex conditions and determine the marker-disease distance in a specific case using this equation. METHODS: Lewontin's linkage disequilibrium (LD) measure D' was used to formulate an equation for mapping disease genes in the presence of phenocopies, locus heterogeneity, gene-gene and gene-environment interactions, incomplete penetrance, uncertain liability and threshold, incomplete initial LD, natural selection, recurrent mutation, high disease allele frequency and unknown mode of inheritance. This equation was then used to determine the distance between a marker ( epsilon 4 within the apolipoprotein E gene, APOE) and Alzheimer's disease (AD) loci using published data. RESULTS: An equation was formulated for mapping disease genes under the above conditions.If these conditions are present but ignored, then recombination fraction theta between marker and disease loci will be either overestimated or estimated with little bias. Therefore, an upper limit of theta can be obtained. AD has been found to be associated with the marker allele epsilon 4 in Africans, Asians, and Caucasians. This suggests that the AD- epsilon 4 allelic LD predates the divergence of peoples occurring 100 000 years ago. With the age of AD- epsilon 4 allelic LD so estimated, the maximal distance was calculated to be 23.2 kb (mean 5.8 kb). CONCLUSIONS: (1) A method is developed for LD mapping of susceptibility genes. (2) A mutation within the APOE gene itself, among others, is responsible for the susceptibility to AD, which is supported by recent evidence from studies using transgenic mice.

Alzheimer Disease↗
PubMed2001

A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.

Osteoporosis is a complex disease that affects >10 million people in the United States and results in 1.5 million fractures annually. In addition, the high prevalence of osteopenia (low bone mass) in the general population places a large number of people at risk for developing the disease. In an effort to identify genetic factors influencing bone density, we characterized a family that includes individuals who possess exceptionally dense bones but are otherwise phenotypically normal. This high-bone-mass trait (HBM) was originally localized by linkage analysis to chromosome 11q12-13. We refined the interval by extending the pedigree and genotyping additional markers. A systematic search for mutations that segregated with the HBM phenotype uncovered an amino acid change, in a predicted beta-propeller module of the low-density lipoprotein receptor-related protein 5 (LRP5), that results in the HBM phenotype. During analysis of >1,000 individuals, this mutation was observed only in affected individuals from the HBM kindred. By use of in situ hybridization to rat tibia, expression of LRP5 was detected in areas of bone involved in remodeling. Our findings suggest that the HBM mutation confers a unique osteogenic activity in bone remodeling, and this understanding may facilitate the development of novel therapies for the treatment of osteoporosis.

Alleles↗
PubMedDate not supplied

Evidence for a major gene underlying bone size variation in the Chinese.

Osteoporosis is a major public health problem defined as a loss of bone strength, of which bone size is an important determinant. In the present study, familial correlation and segregation analyses for the spine and hip bone sizes were performed for the first time in a Chinese sample composed of 393 nuclear families with a total of 1,193 individuals. The results indicate a major gene of codominant inheritance for spine bone size; however, there is no evidence of a major gene influencing hip bone size. Significant familial residual effects are found for both traits, suggesting their polygenic inheritance. Heritability estimates (+/-SE) for spine and hip bone size were 0.62 (0.13) and 0.59 (0.12), respectively. Sex and age differences in genotype-specific average bone size were observed. Compared with our previous study on bone mineral density (BMD) in the same population, this study suggests that genetic determination of bone size may be different from that of BMD, and thus studying bone size as one surrogate phenotype for osteoporotic fractures may be necessary.

Absorptiometry, Photon↗
PubMedDate not supplied

Race and sex differences and contribution of height: a study on bone size in healthy Caucasians and Chinese.

Osteoporosis is characterized by a loss of bone strength, of which bone size (BS) is an important determinant. However, studies on the factors determining BS are relatively few. The present study evaluated the independent effects of height, age, weight, sex, and race on areal BS at the hip and spine, measured by dual-energy X-ray absorptiometry, while focusing on the differential contributions of height to BS across sex, race, and skeletal site. The subjects were aged 40 years or older, including 763 Chinese (384 males and 379 females) from Shanghai, People's Republic of China, and 424 Caucasians (188 males and 236 females) from Omaha, Nebraska. Basically, Caucasians had significantly larger BS than Chinese. After adjusting for height, age, and weight, the Chinese had similar spine BS, but significantly larger intertrochanter BS in both sexes and larger total hip BS in females compared with Caucasians. Males had significantly larger BS than females before and after adjustment in both ethnic groups. The effects of age, weight, and race varied, depending on skeletal site. As expected, height had major effects on BS variation in both sexes and races. Height tended to account for larger BS variation at the spine than at the hip (except for Chinese females), and larger BS variation in Caucasians than in Chinese of the same sex (except for the trochanter in females). We conclude that height is a major predictor for BS, and its contributions vary across sex, race, and skeletal site.

Absorptiometry, Photon↗