Kwok J B, Adams L J, Salmon J A, Donald J A, Mitchell P B, Schofield P R
Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Am J Med Genet. 1999 Feb 5;88(1):99-102. doi: 10.1002/(sici)1096-8628(19990205)88:1<99::aid-ajmg18>3.0.co;2-9.
Straub et al. [1994: Nat Genet 8:291-296] reported a candidate bipolar affective disorder (BAD) locus on chromosome 21q22.3. As a replication study, we analyzed 12 Australian BAD pedigrees for the presence of excess allele sharing and cosegregation with the putative chromosome 21q22.3 BAD locus, using six microsatellite markers. The nonparametric simulation-based statistic SimAPM produced positive results for the marker PFKL (P < 0.001) and D21S198 (P = 0.007). PFKL also demonstrated linkage (P < 0.001) when analyzed using the more conservative statistic, SimIBD. Comparable results were obtained when using the original APM statistic (P = 0.02 for D21S198). However, other nonparametric analyses such as GENEHUNTER and model-free linkage (MFLINK) analysis did not yield significant results. Combined LOD scores for the 12 families were strongly negative for all six markers under six genetic models. Two-point and multipoint analyses of individual families revealed one family, family 17, with maximal LOD scores greater than 1.41 for the 10.5-cM region between PFKL and D21S198. This report provides additional support for the suggestive linkage of a susceptibility locus for BAD on chromosome 21q22.3.
施特劳布等人[1994年：《自然遗传学》8：291 - 296]报告称在21号染色体q22.3区域发现了一个双相情感障碍（BAD）候选基因座。作为一项重复研究，我们使用六个微卫星标记，分析了12个澳大利亚BAD家系，以检测是否存在等位基因共享过剩以及与假定的21号染色体q22.3区域BAD基因座的共分离情况。基于非参数模拟的统计量SimAPM在标记PFKL（P < 0.001）和D21S198（P = 0.007）上得出了阳性结果。当使用更保守的统计量SimIBD进行分析时，PFKL也显示出连锁关系（P < 0.001）。使用原始的APM统计量时也获得了类似结果（D21S组蛋白的P值为0.02）。然而，其他非参数分析，如GENEHUNTER和无模型连锁（MFLINK）分析，并未得出显著结果。在六种遗传模型下，这12个家系中所有六个标记的组合LOD分数均为强阴性。对各个家系的两点和多点分析显示，有一个家系（家系17）在PFKL和D21S198之间10.5厘摩区域的最大LOD分数大于1.41。本报告为21号染色体q22.3区域存在BAD易感基因座的提示性连锁提供了额外支持。
