title: Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24.
abstract: Genome-wide linkage analyses performed in a Finnish study sample have identified four potential predisposing loci for multiple sclerosis (MS). Here we made an effort to restrict the wide linkage region on chromosome 17 with a dense set of 31 markers using multipoint linkage analyses and monitoring for shared marker alleles in MS chromosomes. We carried out the linkage analyses in 22 Finnish multiplex MS families originating from a regional subisolate that shows an exceptionally high prevalence of MS in order to minimize the genetic and environmental heterogeneity of the study sample. Thirty markers on the 23 cM initial interval gave positive pairwise LOD scores. We monitored for shared haplotypes among affected family members within a family, and identified an approximately 4 cM region flanked by the markers D17S1792 and ATA43A10 in 17 out of the 22 families (77.3%). The multipoint linkage analyses using Genehunter and SIMWALK 2.40 provided further evidence for the same 4 cM region, for example a maximal multipoint NPL score of 5.98 (P<0.0002). We observed nominal evidence for association to MS, with one marker flanking the shared region, and this association was replicated in the additional set of families. Using the combined power of linkage, association and shared haplotype analyses, we were thus able to restrict the MS locus on chromosome 17q from 23 cM to a 4 cM region covering a physical interval of approximately 2.5 Mb. Thus, this study describes the restriction of an MS locus outside the HLA region into a segment approachable by molecular tools.
authors.affiliation: Department of Human Genetics, UCLA School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Janna
authors.initials: J
authors.lastname: Saarela
authors.forename: Marlena
authors.initials: M
authors.lastname: Schoenberg Fejzo
authors.forename: Daniel
authors.initials: D
authors.lastname: Chen
authors.forename: Saara
authors.initials: S
authors.lastname: Finnilä
authors.forename: Maikki
authors.initials: M
authors.lastname: Parkkonen
authors.forename: Satu
authors.initials: S
authors.lastname: Kuokkanen
authors.forename: Eric
authors.initials: E
authors.lastname: Sobel
authors.forename: Pentti J
authors.initials: PJ
authors.lastname: Tienari
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Sumelahti
authors.forename: Juhani
authors.initials: J
authors.lastname: Wikström
authors.forename: Irina
authors.initials: I
authors.lastname: Elovaara
authors.forename: Keijo
authors.initials: K
authors.lastname: Koivisto
authors.forename: Tuula
authors.initials: T
authors.lastname: Pirttilä
authors.forename: Mauri
authors.initials: M
authors.lastname: Reunanen
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D002886:Chromosomes, Human, Pair 17; D005387:Finland; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009103:Multiple Sclerosis / Q000235:genetics*; D020161:Physical Chromosome Mapping
chemical_list: D005819:Genetic Markers