First-stage autosomal genome screen in extended pedigrees suggests genes predisposing to low bone mineral density on chromosomes 1p, 2p and 4q
First-stage autosomal genome screen in extended pedigrees suggests genes predisposing to low bone mineral density on chromosomes 1p, 2p and 4q
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DOI：
10.1038/sj.ejhg.5200169
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发表时间：
1998-03-01
影响因子：
5.2
通讯作者：
Spotila, LD
中科院分区：
文献类型：
--
作者：
Devoto, M;Shimoya, K;Spotila, LD
骨质疏松症的特点是骨密度低，而骨质减少在美国每年造成 150 万例骨折。(1) 为了确定基因组中可能含有骨质减少倾向基因的区域，我们对七个患有低骨矿物质密度 (BMD) 复发的大谱系的 149 名成员进行了基因分型，其中 330 个 DNA 标记分布在整个常染色体基因组中。该数量性状的连锁分析是使用脊柱和髋部 BMD 值通过经典的 led-score 方法使用遗传模型和从七个家族估计的参数进行的。此外，还使用传统的 Haseman-Elston 方法对来自同一谱系的 74 对独立同胞进行了非参数分析。对于 11q 染色体上的标记 CD3D，通过所有家族参数分析获得的最大 lod 得分为 + 2.08 (theta = 0.05)。参数分析的所有其他综合对数值均小于+1.90，即暗示性关联的阈值。非参数分析表明低 BMD 与染色体 1p36（D1S450 的 Z(max) = + 3.51）和 2p23-24（D2S149 的 Z(max) = + 2.07）存在连锁。这些区域的最大多点 lod 分数分别为 +2.29 和 +2.25。在单点和多点非参数分析中，相关 lod 得分高于暗示性连锁阈值的第三个区域位于染色体 4qter（对于 D4S1539，Z(max) = + 2.95；对于 D4S1554，Z(max) = + 2.48）。我们的数据表明存在多个参与控制脊柱和髋部 BMD 的基因，并指出了在该样本和其他独立样本中需要进一步筛选的几个候选区域。
Osteoporosis is characterized by low bone density, and osteopenia is responsible for 1.5 million fractures in the United States annually.(1) In order to identify regions of the genome which are likely to contain genes predisposing to osteopenia, we genotyped 149 members of seven large pedigrees having recurrence of low bone mineral density (BMD) with 330 DNA markers spread throughout the autosomal genome. Linkage analysis for this quantitative trait was carried out using spine and hip BMD values by the classical led-score method using a genetic model with parameters estimated from the seven families. In addition, non-parametric analysis was performed using the traditional Haseman-Elston approach in 74 independent sib pairs from the same pedigrees. The maximum lod score obtained by parametric analysis in all families combined was + 2.08 (theta = 0.05) for the marker CD3D on chromosome 11q. All other combined lod scores from the parametric analysis were less than +1.90, the threshold for suggestive linkage. Non-parametric analysis suggested linkage of low BMD to chromosomes 1p36 (Z(max) = + 3.51 for D1S450) and 2p23-24 (Z(max) = + 2.07 for D2S149). Maximum multi-point lod scores for these regions were +2.29 and +2.25, respectively. A third region with associated lod scores above the threshold of suggestive linkage in both single-point and multi-point non-parametric analysis was on chromosome 4qter (Z(max) = + 2.95 for D4S1539 and Z(max) = + 2.48 for D4S1554). Our data suggest the existence of multiple genes involved in controlling spine and hip BMD, and indicate several candidate regions for further screening in this and other independent samples.