The Finnish genetic heritage in 2022 – from diagnosis to translational research

• Published in: Disease models & mechanisms Vol. 15; no. 10
• Main Authors: Uusimaa, Johanna, Kettunen, Johannes, Varilo, Teppo, Järvelä, Irma, Kallijärvi, Jukka, Kääriäinen, Helena, Laine, Minna, Lapatto, Risto, Myllynen, Päivi, Niinikoski, Harri, Rahikkala, Elisa, Suomalainen, Anu, Tikkanen, Ritva, Tyynismaa, Henna, Vieira, Päivi, Zarybnicky, Tomas, Sipilä, Petra, Kuure, Satu, Hinttala, Reetta
• Format: Journal Article
• Language: English
• Published: Cambridge The Company of Biologists Ltd 01-10-2022; The Company of Biologists
• Subjects: Anemia; big data; Blood; Congenital diseases; Disease; DNA methylation; DNA polymerase; Enzymes; finngen; finnish disease heritage; Genetic counseling; Genetic disorders; Genetic diversity; Genetic drift; Genotypes; Kinases; Mitochondrial DNA; Molecular modelling; monogenic disorders; Mutation; Phenotypes; Population genetics; population isolate; Population studies; Population-based studies; Proteins; rare disease; Review; Subpopulations; Finland
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.049490

Isolated populations have been valuable for the discovery of rare monogenic diseases and their causative genetic variants. Finnish disease heritage (FDH) is an example of a group of hereditary monogenic disorders caused by single major, usually autosomal-recessive, variants enriched in the population due to several past genetic drift events. Interestingly, distinct subpopulations have remained in Finland and have maintained their unique genetic repertoire. Thus, FDH diseases have persisted, facilitating vigorous research on the underlying molecular mechanisms and development of treatment options. This Review summarizes the current status of FDH, including the most recently discovered FDH disorders, and introduces a set of other recently identified diseases that share common features with the traditional FDH diseases. The Review also discusses a new era for population-based studies, which combine various forms of big data to identify novel genotype–phenotype associations behind more complex conditions, as exemplified here by the FinnGen project. In addition to the pathogenic variants with an unequivocal causative role in the disease phenotype, several risk alleles that correlate with certain phenotypic features have been identified among the Finns, further emphasizing the broad value of studying genetically isolated populations.