Econs Michael J, Koller Daniel L, Hui Siu L, Fishburn Tonya, Conneally P Michael, Johnston C Conrad, Peacock Munro, Foroud Tatiana M
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Am J Hum Genet. 2004 Feb;74(2):223-8. doi: 10.1086/381401. Epub 2004 Jan 16.
Peak bone mineral density (BMD) is a highly heritable trait and is a good predictor of the risk of osteoporosis and fracture in later life. Recent studies have sought to identify the genes underlying peak BMD. Linkage analysis in a sample of 464 premenopausal white sister pairs detected linkage of spine BMD to chromosome 1q (LOD 3.6). An independent sample of 254 white sister pairs has now been genotyped, and it also provides evidence of linkage to chromosome 1q (LOD 2.5) for spine BMD. Microsatellite markers were subsequently genotyped for a 4-cM map in the chromosome 1q region in all available white sister pairs (n=938), and a LOD score of 4.3 was obtained near the marker D1S445. Studies in the mouse have also detected evidence of linkage to BMD phenotypes in the region syntenic to our linkage finding on chromosome 1q. Thus, we have replicated a locus on 1q contributing to BMD at the spine and have found further support for the region in analyses employing an enlarged sample. Studies are now ongoing to identify the gene(s) contributing to peak spine BMD in women.
峰值骨密度（BMD）是一种高度可遗传的性状，是预测晚年骨质疏松症和骨折风险的良好指标。最近的研究试图确定峰值骨密度背后的基因。对464对绝经前白人姐妹样本进行的连锁分析发现，脊柱骨密度与1号染色体q臂存在连锁关系（LOD值为3.6）。现在对254对白人姐妹的独立样本进行了基因分型，该样本也为脊柱骨密度与1号染色体q臂的连锁关系提供了证据（LOD值为2.5）。随后，对所有可用的白人姐妹对（n = 938）在1号染色体q臂区域进行了4厘摩图谱的微卫星标记基因分型，在标记D1S445附近获得了4.3的LOD分数。对小鼠的研究也发现了与我们在1号染色体q臂上的连锁发现同区域的骨密度表型存在连锁关系的证据。因此，我们在1号染色体q臂上复制了一个与脊柱骨密度相关的基因座，并在采用扩大样本的分析中为该区域找到了进一步的支持。目前正在进行研究以确定导致女性脊柱峰值骨密度的基因。
