Mustanski Brian S, Dupree Michael G, Nievergelt Caroline M, Bocklandt Sven, Schork Nicholas J, Hamer Dean H
Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hum Genet. 2005 Mar;116(4):272-8. doi: 10.1007/s00439-004-1241-4. Epub 2005 Jan 12.
This is the first report of a full genome scan of sexual orientation in men. A sample of 456 individuals from 146 families with two or more gay brothers was genotyped with 403 microsatellite markers at 10-cM intervals. Given that previously reported evidence of maternal loading of transmission of sexual orientation could indicate epigenetic factors acting on autosomal genes, maximum likelihood estimations (mlod) scores were calculated separated for maternal, paternal, and combined transmission. The highest mlod score was 3.45 at a position near D7S798 in 7q36 with approximately equivalent maternal and paternal contributions. The second highest mlod score of 1.96 was located near D8S505 in 8p12, again with equal maternal and paternal contributions. A maternal origin effect was found near marker D10S217 in 10q26, with a mlod score of 1.81 for maternal meioses and no paternal contribution. We did not find linkage to Xq28 in the full sample, but given the previously reported evidence of linkage in this region, we conducted supplemental analyses to clarify these findings. First, we re-analyzed our previously reported data and found a mlod of 6.47. We then re-analyzed our current data, after limiting the sample to those families previously reported, and found a mlod of 1.99. These Xq28 findings are discussed in detail. The results of this first genome screen for normal variation in the behavioral trait of sexual orientation in males should encourage efforts to replicate these findings in new samples with denser linkage maps in the suggested regions.
这是关于男性性取向全基因组扫描的首份报告。对来自146个家庭、有两个或更多同性恋兄弟的456名个体样本,使用403个微卫星标记,按10厘摩间隔进行基因分型。鉴于先前报道的性取向遗传中母系传递负荷的证据可能表明表观遗传因素作用于常染色体基因,分别计算了母系、父系及综合传递的最大似然估计(mlod)分数。在7q36靠近D7S798的位置,最高mlod分数为3.45,母系和父系贡献大致相等。第二高的mlod分数1.96位于8p12靠近D8S505的位置,同样母系和父系贡献相等。在10q26靠近标记D10S217处发现母系起源效应,母系减数分裂的mlod分数为1.81,无父系贡献。在整个样本中未发现与Xq28的连锁关系,但鉴于先前报道的该区域连锁证据,我们进行了补充分析以阐明这些发现。首先,我们重新分析了先前报道的数据,发现mlod为6.47。然后,在将样本限制为先前报道的那些家庭后,我们重新分析了当前数据,发现mlod为1.99。对这些Xq28的发现进行了详细讨论。首次针对男性性取向行为特征正常变异的基因组筛查结果应促使人们努力在建议区域内具有更密集连锁图谱的新样本中重复这些发现。