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Is Population Bone Mineral Density Variation Linked to the Marker D11S987 On Chromosome 11q12–13?

Osteoporosis Research Center (H.-W.D., F.-H.X., T.C., X.-T.D., J.-L.L., K.M.D., H.D., M.J., R.R.R.) and Department of Biomedical Sciences (H.-W.D., F.-H.X., X.-T.D., J.-L.L.), Creighton University, Omaha, Nebraska 68131; and Laboratory of Molecular and Statistical Genetics (H.-W.D.), Hunan Normal University, ChangSha, Hunan 410081, P. R. China

Address all correspondence and requests for reprints to: Hong-Wen Deng, Ph.D., Osteoporosis Research Center, Creighton University, 601 North 30th Street Suite 6787, Omaha, Nebraska 68131. E-mail: deng{at}creighton.edu

Abstract

Our purpose is to test linkage of human chromosome 11q12–13 to BMD variation. Chromosome 11q12–13 has been linked to three BMD-related phenotypes that are inherited as Mendelian traits in human pedigrees: an autosomal dominant high bone mass trait, autosomal recessive osteoporosis pseudoglioma, and autosomal recessive osteopetrosis. A sibling pair study with 374 sibships showed significant linkage of D11S987 to normal BMD variation, with a maximum logarithm of odds score of 3.5. However, a subsequent linkage study with a total of 595 sibling pairs demonstrated reduced significance for linkage of D11S987 to bone mineral density variation, with a logarithm of odds score less than 2.2. We genotyped five markers in a genomic region of 27 cM centering on D11S987 and measured bone mineral density and other traits (weight, etc.) for 635 individuals from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with bone mineral density Z-scores less than -1.28 at the hip or spine. Adjusting for age, sex, and weight as covariates, we performed two-point and multipoint linkage analyses using the variance component linkage analysis method implemented in Sequential Oligogenic Linkage Analysis Routines. We found little evidence of linkage of these five markers to bone mineral density at the spine, hip, wrist and total body bone mineral content. The maximum logarithm of odds score at these five markers was 0.25, and the maximum logarithm of odds score at D11S987 was 0.15. Therefore, although we cannot exclude the linkage of D11S987 region to bone mineral density variation, there is no evidence for linkage of the marker D11S987 on human chromosome 11q12–13 to bone mineral density variation in our study population.

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