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17 March 2003

Cortical index and size of hand bones: segregation analysis and linkage with the 11q12-13 segment.

Zvi Cohen, Leonid Kalichman, Eugene Kobyliansky, Ida Malkin, Eliana Almog, Gregory Livshits

Med Sci Monit 2003; 9(3): MT13-20 :: ID: 4722

Abstract

BACKGROUND: Bone geometry (BG) and size (BS) are important factors in determining bone fragility. Previous studies have suggested that more than half of BG and BS variation is genetically determined. The possible chromosomal locations of genes involved in BS and BG determination have not been explored. We evaluated the extent and mode of inheritance of the radiographic hand BS index (BSI) and the metacarpal cortical index (MCI), and tested the hypothesis of linkage between these traits and the 11q 12-13 chromosomal region. MATERIAL/METHODS: Hand radiographs and blood samples were collected from 1190 individuals belonging to 349 Chuvasha nuclear families (Russian Federation). Segregation analysis was conducted on a total sample. Transmission disequilibrium testing (TDT) and model-based linkage analyses (MBLA) were performed on a sub-sample of 163 families. RESULTS: The hypothesis of a major gene effect was confirmed for both studied traits. The best-fitting models were Mendelian, with an additive type of inheritance. The inferred major gene explained 50% of the CI and 40% of the BSI variation. The TDT and MBLA results did not permit confirmation of hypotheses about linkage between hand BSI and the 11q 12-13 chromosomal region, but a possible linkage between CI and that region cannot be ruled out. CONCLUSIONS: We support the hypothesis of a major gene effect in the heritability of BSI and MCI. We provide suggestive evidence for possible linkage disequilibrium between MCI and the 11q12-13 chromosomal segment (marker D11S1983), but not for a linkage between BSI and this segment

Keywords: Bones of Upper Extremity - anatomy & histology, Metacarpus - anatomy & histology

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