Peltonen L, Jalanko A, Varilo T
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Hum Mol Genet. 1999;8(10):1913-23. doi: 10.1093/hmg/8.10.1913.
Finland, located at the edge of the inhabitable world, is one of the best-studied genetic isolates. The characteristic features of population isolates-founder effect, genetic drift and isolation-have, over the centuries, shaped the gene pool of the Finns. Finnish diseases have been a target of extensive genetic research and the majority of some 35 disease genes enriched in this population have been identified; the molecular and cellular consequences of disease mutations are currently being characterized. Special strategies taking advantage of linkage disequilibrium have been efficiently used in the initial mapping and restriction of Finnish disease loci and this has stimulated development of novel statistical approaches in the disease gene hunt. Identification of mutated genes has provided tools for detailed analyses of molecular pathogenesis in Finnish diseases, many of which reveal a distinct tissue specificity of clinical phenotype. Often these studies have not only clarified the molecular detail of Finnish diseases, but also provided novel information on biological processes and metabolic pathways essential for normal development and function of human cells and tissues.
芬兰位于可居住世界的边缘，是研究最为深入的遗传隔离群之一。几个世纪以来，群体隔离的特征——奠基者效应、遗传漂变和隔离——塑造了芬兰人的基因库。芬兰疾病一直是广泛遗传研究的对象，目前已鉴定出约35种在该群体中富集的疾病基因中的大多数；目前正在对疾病突变的分子和细胞后果进行表征。利用连锁不平衡的特殊策略已有效地用于芬兰疾病基因座的初步定位和限制，这推动了疾病基因搜寻中新型统计方法的发展。突变基因的鉴定为芬兰疾病分子发病机制的详细分析提供了工具，其中许多疾病揭示了临床表型具有明显的组织特异性。这些研究通常不仅阐明了芬兰疾病的分子细节，还提供了有关人类细胞和组织正常发育和功能所必需的生物过程和代谢途径的新信息。
