Ekholm Jenny M, Kieseppä Tuula, Hiekkalinna Tero, Partonen Timo, Paunio Tiina, Perola Markus, Ekelund Jesper, Lönnqvist Jouko, Pekkarinen-Ijäs Petra, Peltonen Leena
Department of Molecular Medicine, National Public Health Institute, 00251 Helsinki, Finland.
Hum Mol Genet. 2003 Aug 1;12(15):1907-15. doi: 10.1093/hmg/ddg199.
We performed a genome-wide scan for susceptibility loci in bipolar disorder in a study sample colleted from the isolated Finnish population, consisting of 41 families with at least two affected siblings. We identified one distinct locus on 16p12 providing significant evidence for linkage in two-point analysis (Z(max)=3.4). Furthermore, three loci with a two-point LOD score >2.0 were observed with markers on 4q32, 12q23 and Xq25, the latter locus having been earlier identified in one extended Finnish pedigree. In the second stage we fine mapped these chromosomal regions and also genotyped additional family members. In the fine mapping stage, 4q32 provided significant evidence of linkage for the three-point analyses (Z(max)=3.6) and 16p12 produced a three-point LOD score of 2.7. Since the identified chromosomal regions replicate earlier linkage findings in either bipolar disorder or other mental disorders, they should be considered good targets for further genetic analyses.
我们在从芬兰隔离人群中收集的一个研究样本中，对双相情感障碍的易感基因座进行了全基因组扫描，该样本由41个至少有两个患病同胞的家庭组成。我们在16p12上鉴定出一个独特的基因座，在两点分析中提供了显著的连锁证据（Z(max)=3.4）。此外，在4q32、12q23和Xq25的标记上观察到三个两点LOD得分>2.0的基因座，后一个基因座此前已在一个芬兰大家庭中被鉴定出来。在第二阶段，我们对这些染色体区域进行了精细定位，并对其他家庭成员进行了基因分型。在精细定位阶段，4q32在三点分析中提供了显著的连锁证据（Z(max)=3.6），16p12产生了2.7的三点LOD得分。由于所鉴定的染色体区域重复了双相情感障碍或其他精神障碍中早期的连锁发现，因此它们应被视为进一步基因分析的良好靶点。
