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VOOZH | about |
%611738
Table of Contents
Cytogenetic location: 20p12.3 Genomic coordinates (GRCh38) : 20:5,100,001-9,200,000
For a discussion of genetic heterogeneity of bone mineral density (BMD), see BMND1 (601884).
Using an 'affected-only' approach defined by BMD values at both the spine and the hip in combination with osteoporotic fractures, Styrkarsdottir et al. (2003) performed multipoint allele-sharing linkage analysis in 1,323 individuals from 207 extended Icelandic families with osteoporosis and identified linkage to chromosome 20p12.3 (lod score, 5.10; corrected p value = 1.6 x 10(-6)). Fine mapping and haplotype analyses showed the strongest association in the region of the BMP2 gene (112261); sequencing BMP2 in 188 patients and 94 controls revealed a missense polymorphism (S37A) and 2 SNP haplotypes that were associated with osteoporosis (166710). A replication study in postmenopausal Danish women, in one group with persistently low BMD and another with osteoporotic fracture, showed a significant association for haplotype 'C' (p = 0.0038) for low BMD, whereas S37A and haplotype 'B' were nominally significant for osteoporotic fractures and low BMD, respectively.
Kung et al. (2010) performed a genomewide association study in 800 unrelated Southern Chinese women with extreme BMD (high or low), followed by replication studies in 6 independent study populations of European descent and Asian populations involving 18,098 individuals. In the metaanalysis, a SNP (rs2273061) in intron 3 of the JAG1 gene (601920) was associated with high BMD (p = 5.27 x 10(-8) and p = 4.15 x 10(-5) for lumbar spine and femoral neck, respectively) and was further found to be associated with low risk of osteoporotic fracture (p = 0.009; odds ratio, 0.7). Regionwide and haplotype analyses showed that the strongest evidence for association was from a linkage disequilibrium block that included rs2273061 (p = 8.52 x 10(-9) and 3.47 x 10(-5) for lumbar spine and femoral neck, respectively).
Kung et al. (2010) performed functional analysis of the BMD-associated SNP (rs2273061) in intron 3 of the JAG1 gene (601920) using EMSA and observed binding of MYC (190080) to the 'G' but not the 'A' allele; mRNA expression analysis of bone-derived cells and peripheral blood mononuclear cells confirmed association of the high BMD-related G allele with higher JAG1 expression. Kung et al. (2010) concluded that JAG1 is a candidate gene for BMD regulation.
Kung, A. W. C., Xiao, S.-M., Cherny, S., Li, G. H. Y., Gao, Y., Tso, G., Lau, K. S., Luk, K. D. K., Liu, J., Cui, B., Zhang, M.-J., Zhang, Z., and 21 others. Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies. Am. J. Hum. Genet. 86: 229-239, 2010. [PubMed: 20096396, images, related citations] [Full Text]
Styrkarsdottir, U., Cazier, J.-B., Kong, A., Rolfsson, O., Larsen, H., Bjarnadottir, E., Johannsdottir, V. D., Sigurdardottir, M. S., Bagger, Y., Christiansen, C., Reynisdottir, I., Grant, S. F. A., Jonasson, K., Frigge, M. L., Gulcher, J. R., Sigurdsson, G., Stefansson, K. Linkage of osteoporosis to chromosome 20p12 and association to BMP2. PLoS Biol. 1: e69, 2003. Note: Electronic Article. [PubMed: 14691541, images, related citations] [Full Text]
Cytogenetic location: 20p12.3 Genomic coordinates (GRCh38) : 20:5,100,001-9,200,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 20p12.3 | {Osteoporosis} | 166710 | Autosomal dominant | 2 |
For a discussion of genetic heterogeneity of bone mineral density (BMD), see BMND1 (601884).
Using an 'affected-only' approach defined by BMD values at both the spine and the hip in combination with osteoporotic fractures, Styrkarsdottir et al. (2003) performed multipoint allele-sharing linkage analysis in 1,323 individuals from 207 extended Icelandic families with osteoporosis and identified linkage to chromosome 20p12.3 (lod score, 5.10; corrected p value = 1.6 x 10(-6)). Fine mapping and haplotype analyses showed the strongest association in the region of the BMP2 gene (112261); sequencing BMP2 in 188 patients and 94 controls revealed a missense polymorphism (S37A) and 2 SNP haplotypes that were associated with osteoporosis (166710). A replication study in postmenopausal Danish women, in one group with persistently low BMD and another with osteoporotic fracture, showed a significant association for haplotype 'C' (p = 0.0038) for low BMD, whereas S37A and haplotype 'B' were nominally significant for osteoporotic fractures and low BMD, respectively.
Kung et al. (2010) performed a genomewide association study in 800 unrelated Southern Chinese women with extreme BMD (high or low), followed by replication studies in 6 independent study populations of European descent and Asian populations involving 18,098 individuals. In the metaanalysis, a SNP (rs2273061) in intron 3 of the JAG1 gene (601920) was associated with high BMD (p = 5.27 x 10(-8) and p = 4.15 x 10(-5) for lumbar spine and femoral neck, respectively) and was further found to be associated with low risk of osteoporotic fracture (p = 0.009; odds ratio, 0.7). Regionwide and haplotype analyses showed that the strongest evidence for association was from a linkage disequilibrium block that included rs2273061 (p = 8.52 x 10(-9) and 3.47 x 10(-5) for lumbar spine and femoral neck, respectively).
Kung et al. (2010) performed functional analysis of the BMD-associated SNP (rs2273061) in intron 3 of the JAG1 gene (601920) using EMSA and observed binding of MYC (190080) to the 'G' but not the 'A' allele; mRNA expression analysis of bone-derived cells and peripheral blood mononuclear cells confirmed association of the high BMD-related G allele with higher JAG1 expression. Kung et al. (2010) concluded that JAG1 is a candidate gene for BMD regulation.
Kung, A. W. C., Xiao, S.-M., Cherny, S., Li, G. H. Y., Gao, Y., Tso, G., Lau, K. S., Luk, K. D. K., Liu, J., Cui, B., Zhang, M.-J., Zhang, Z., and 21 others. Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies. Am. J. Hum. Genet. 86: 229-239, 2010. [PubMed: 20096396] [Full Text: https://doi.org/10.1016/j.ajhg.2009.12.014]
Styrkarsdottir, U., Cazier, J.-B., Kong, A., Rolfsson, O., Larsen, H., Bjarnadottir, E., Johannsdottir, V. D., Sigurdardottir, M. S., Bagger, Y., Christiansen, C., Reynisdottir, I., Grant, S. F. A., Jonasson, K., Frigge, M. L., Gulcher, J. R., Sigurdsson, G., Stefansson, K. Linkage of osteoporosis to chromosome 20p12 and association to BMP2. PLoS Biol. 1: e69, 2003. Note: Electronic Article. [PubMed: 14691541] [Full Text: https://doi.org/10.1371/journal.pbio.0000069]
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