2009 © Institute for Molecular Medicine Finland FIMM
Research Director Janna Saarela, MD, PhD, FIMM Technology Centre
Dr Saarela’s research group is focusing on genetics of complex neuropsychiatric diseases using cutting edge genetic technologies. By taking advantage of the well characterized clinical samples from Finnish population isolates and the large Finnish population cohorts her group has identified novel genes responsible for multiple sclerosis in collaboration with Professor Peltonen’s group and the International Multiple Sclerosis Genetics Consortium (IMSGC). Additionally her group is actively testing, optimizing and further developing novel genomics and genetics methods and analysis pipelines with the FIMM Technology Centre.
Multiple sclerosis (MS) is one of the most common neurological diseases of young adults with a prevalence of 100-150/100000 in Northern European populations. It is a complex inflammatory disease of the central nervous system with presumed autoimmune etiology. Both environmental and genetic factors are thought to contribute to the development of MS and the genetic risk factors likely include both common and rare risk alleles. The role of the HLA locus and specially the HLA-DRB1*1501 has been established for over a decade, but recent genome-wide association studies (GWAS) and subsequent meta-analysis have identified novel MS loci: IL2RA, IL7R, CLEC16A, CD58, TNFRSF1A, IRF8, and TYK2. Most of these associated variants are common, have small odds ratios and explain only a fraction of the genetic risk. Currently there is no known cure for MS and the diagnosis is often delayed because two separate episodes of neurologic symptoms characteristic of MS are required for a definitive MS diagnosis. Thus, identification of the predisposing genes will shed light to the biological pathways and mechanisms behind MS and will enable functional studies and development of more accurate diagnosis and treatment for the disease.
Dr Saarela’s group takes advantage of the population history of Finland and the province of Southern Ostrobothnia, which is an old internal isolate with increased prevalence and familial occurrence of MS, in search for genes predisposing to the disease. We hypothesize that some variants predisposing to MS have either become enriched in Southern Ostrobothnia or can be more easily detected against a homogenous allelic background using cutting edge genetic technologies like high density SNP screens and targeted next-generation sequencing of the associated loci. We are also utilizing multiplex MS families originating from the high-risk isolate to look for potential rare, even family specific MS variants.
Key publications:
Jakkula E, Leppä V, Sulonen A-M, Varilo T, Kallio S, Kemppinen A, Purcell S, Koivisto K, Tienari PJ, Sumelahti M-L, Elovaara I, Pirttilä T, Reunanen M, Aromaa A, Oturai A, Søndergaard H, Harbo HF, Mero I-L, Gabriel SB, Mirel DB, Hauser SL, Kappos L, Polman C, De Jager PL, Hafler DA, Daly MJ, Palotie A, Saarela J, and Peltonen L. Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene. Am J Hum genet, in press
Kallio SP, Jakkula E, Purcell S, Suvela M, Koivisto K, Tienari PJ, Elovaara I, Pirttilä T, Reunanen M, Bronnikov D, Viander M, Meri S, Hillert J, Lundmark F, Harbo HF, Lorentzen AR, De Jager PL, Daly MJ, Hafler DA, Palotie A, Peltonen L, Saarela J. Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS. Hum Mol Genet. 2009 May 1;18(9):1670-83.
Silander K, Saarela J. Whole genome amplification with Phi29 DNA polymerase to enable genetic or genomic analysis of samples of low DNA yield. Methods Mol Biol. 2008;439:1-18.
Lundmark F, Duvefelt K, Iacobaeus E, Kockum I, Wallström E, Khademi M, Oturai A, Ryder LP, Saarela J, Harbo HF, Celius EG, Salter H, Olsson T, Hillert J. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat Genet. 2007 Sep;39(9):1053-4.