Saar Kathrin, Geller Frank, Rüschendorf Franz, Reis André, Friedel Susann, Schäuble Nadine, Nürnberg Peter, Siegfried Wolfgang, Goldschmidt Hans-Peter, Schäfer Helmut, Ziegler Andreas, Remschmidt Helmut, Hinney Anke, Hebebrand Johannes
Molecular Genetics and Gene Mapping Center, Max Delbrück Center, Berlin, Germany.
Pediatrics. 2003 Feb;111(2):321-7. doi: 10.1542/peds.111.2.321.
Several genome scans have been performed for adult obesity. Because single formal genetic studies suggest a higher heritability of body weight in adolescence and because genes that influence body weight in adulthood might not be the same as those that are relevant in childhood and adolescence, we performed a whole genome scan.
The genome scan was based on 89 families with 2 or more obese children (sample 1). The mean age of the index patients was 13.63 +/- 2.75 years. A total of 369 individuals were initially genotyped for 437 microsatellite markers. A second sample of 76 families was genotyped using microsatellite markers that localize to regions for which maximum likelihood binomial logarithm of the odd (MLB LOD) scores on use of the concordant sibling pair approach exceeded 0.7 in sample 1.
The regions with MLB LOD scores >0.7 were on chromosomes 1p32.3-p33, 2q37.1-q37.3, 4q21, 8p22, 9p21.3, 10p11.23, 11q11-q13.1, 14q24-ter, and 19p13-q12 in sample 1; MLB LOD scores on chromosomes 8p and 19q exceeded 1.5. In sample 2, MLB LOD scores of 0.68 and 0.71 were observed for chromosomes 10p11.23 and 11q13, respectively.
We consider that several of the peaks identified in other scans also gave a signal in this scan as promising for ongoing pursuits to identify relevant genes. The genetic basis of childhood and adolescent obesity might not differ that much from adult obesity.
已经针对成人肥胖进行了多项全基因组扫描。由于单项正式遗传学研究表明青少年时期体重的遗传度更高,并且影响成年期体重的基因可能与儿童期和青少年期相关的基因不同,因此我们进行了全基因组扫描。
全基因组扫描基于89个有2名或更多肥胖儿童的家庭(样本1)。索引患者的平均年龄为13.63±2.75岁。最初对总共369名个体进行了437个微卫星标记的基因分型。使用微卫星标记对76个家庭的第二个样本进行基因分型,这些微卫星标记定位于在样本1中使用一致同胞对方法时最大似然二项式对数优势(MLB LOD)得分超过0.7的区域。
在样本1中,MLB LOD得分>0.7的区域位于1号染色体的1p32.3 - p33、2号染色体的2q37.1 - q37.3、4号染色体的4q21、8号染色体的8p22、9号染色体的9p21.3、10号染色体的10p11.23、11号染色体的11q11 - q13.1、14号染色体的14q24 - ter以及19号染色体的19p13 - q12;8号染色体p臂和19号染色体q臂的MLB LOD得分超过1.5。在样本2中,10号染色体的10p11.23和11号染色体的11q13的MLB LOD得分分别为0.68和0.71。
我们认为在其他扫描中确定的几个峰值在本次扫描中也给出了信号,有望在正在进行的寻找相关基因的研究中取得进展。儿童期和青少年期肥胖的遗传基础可能与成人肥胖没有太大差异。