Liu Yong-Jun, Xu Fu-Hua, Shen Hui, Liu Yao-Zhong, Deng Hong-Yi, Zhao Lan-Juan, Huang Qing-Yang, Dvornyk Volodymyr, Conway Theresa, Davies K Michael, Li Jin-Long, Recker Robert R, Deng Hong-Wen
Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68131, USA.
J Clin Endocrinol Metab. 2004 Feb;89(2):875-82. doi: 10.1210/jc.2003-030774.
We have recently reported a whole-genome scan in a sample of 630 subjects from 53 extended pedigrees, in which several genomic regions that may contain quantitative trait loci (QTLs) for obesity were suggested. In the present study, with an attempt to confirm our previous findings, we performed a follow-up linkage study in an expanded sample of 79 pedigrees with 1816 subjects (including expanded previous 53 pedigrees and 26 newly recruited pedigrees containing 1058 subjects). A new set of microsatellite markers spanning previously identified regions were selected, with the average genomic distance narrowed from approximately 10 cM to approximately 5 cM in this study. Using a variance component method, we performed two- and multipoint linkage analyses in the following three sample sets: expanded previous 53 pedigrees (758 subjects), 26 new pedigrees, and 79 total pedigrees. For body mass index, analyses of the expanded 53 pedigrees attained a LOD score of 2.32 near marker D1S468 in two-point analysis and a maximum LOD score (MLS) of 2.21 in multipoint analysis; 2q14 near marker D2S347 attained a LOD score of 3.42 in two-point analysis and a MLS of 3.93 in multipoint analysis. The linkage peaks at 1p36 and 2q14 were further supported in the analyses of all 79 pedigrees, with multipoint MLS being 1.38 and 0.90, respectively. For fat mass, genomic region 6q27 achieved a LOD score of 1.24 in two-point analysis and an MLS of 0.92 in multipoint analysis in all 79 pedigrees. Our data support that 1p36, 2q14, and 6q27 are promising regions that may harbor QTLs for obesity phenotypes.
我们最近报道了对来自53个扩展家系的630名受试者样本进行的全基因组扫描，研究中发现了几个可能包含肥胖数量性状基因座（QTL）的基因组区域。在本研究中，为了证实我们之前的发现，我们在一个扩大的样本中进行了后续连锁研究，该样本包括79个家系的1816名受试者（包括之前的53个家系和新招募的26个家系，后者包含1058名受试者）。我们选择了一组新的微卫星标记，这些标记覆盖了之前确定的区域，在本研究中平均基因组距离从约10厘摩缩小到约5厘摩。使用方差成分法，我们在以下三个样本集中进行了两点和多点连锁分析：之前的53个家系（758名受试者）、26个新家系以及79个家系的总和。对于体重指数，在两点分析中，对扩展的53个家系进行分析时，标记D1S468附近的LOD得分为2.32，在多点分析中最大LOD得分（MLS）为2.21；标记D2S347附近的2q14在两点分析中LOD得分为3.42，在多点分析中MLS为3.93。在对所有79个家系的分析中，1p36和2q14处的连锁峰得到了进一步支持，多点MLS分别为1.38和0.90。对于体脂，在所有79个家系中，基因组区域6q27在两点分析中的LOD得分为1.24，在多点分析中的MLS为0.92。我们的数据支持1p36、2q14和6q27是可能含有肥胖表型QTL的有前景的区域。
