Deng H W, Xu F H, Conway T, Deng X T, Li J L, Davies K M, Deng H, Johnson M, Recker R R
Osteoporosis Research Center, Creighton University, Omaha, Nebraska 68131, USA.
J Clin Endocrinol Metab. 2001 Aug;86(8):3735-41. doi: 10.1210/jcem.86.8.7762.
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 approximately 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.
我们的目的是检测人类11号染色体q12 - 13区域与骨密度变异之间的连锁关系。11号染色体q12 - 13区域已与三种与骨密度相关的表型相关联，这些表型在人类家系中按孟德尔遗传方式遗传：一种常染色体显性高骨量性状、常染色体隐性骨质疏松假性胶质瘤和常染色体隐性骨硬化症。一项对374个同胞对的研究表明，D11S987与正常骨密度变异存在显著连锁，最大优势对数得分为3.5。然而，随后一项对总共595个同胞对的连锁研究表明，D11S987与骨矿物质密度变异的连锁显著性降低，优势对数得分小于2.2。我们对以D11S987为中心的约27厘摩的基因组区域中的五个标记进行了基因分型，并测量了来自53个人类家系的635名个体的骨矿物质密度和其他性状（体重等）。每个家系均通过一名在髋部或脊柱处骨矿物质密度Z评分小于 -1.28的先证者确定。将年龄、性别和体重作为协变量进行校正后，我们使用顺序寡基因连锁分析程序中实现的方差成分连锁分析方法进行了两点和多点连锁分析。我们几乎没有发现这五个标记与脊柱、髋部、腕部和全身骨矿物质含量的骨密度存在连锁的证据。这五个标记的最大优势对数得分为0.25，D11S987的最大优势对数得分为0.15。因此，尽管我们不能排除D11S987区域与骨矿物质密度变异之间的连锁关系，但在我们的研究人群中，没有证据表明人类11号染色体q12 - 13上的标记D1S987与骨矿物质密度变异存在连锁关系。
