title: No evidence for shared etiology in two demyelinative disorders, MS and PLOSL.
abstract: Loss-of-function mutations of DAP12 and TREM2 cause a recessively inherited disease PLOSL, manifesting in brain white matter. The genes of the DAP12-TREM2 signaling receptor are located on 19q13.12 and 6p21.1, to which linkage has been observed also in families affected by another immune-mediated demyelinating disease, MS. We have tested if allelic variation in DAP12 or TREM2 predisposes also to MS by monitoring carrier frequency of the Finnish PLOSL mutation in Finnish MS cases and by studying DAP12 and TREM2 in MS by linkage and association. To conclude, the DAP12-TREM2 complex unlikely has a role in genetic susceptibility of MS.
authors.affiliation: Finnish Institute for Molecular Medicine, FIMM, and National Public Health Institute, Biomedicum, Helsinki, Finland.
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Sulonen
authors.forename: Suvi P
authors.initials: SP
authors.lastname: Kallio
authors.forename: Pekka
authors.initials: P
authors.lastname: Ellonen
authors.forename: Minna
authors.initials: M
authors.lastname: Suvela
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: Pentti J
authors.initials: PJ
authors.lastname: Tienari
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Janna
authors.initials: J
authors.lastname: Saarela
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001927:Brain Diseases / Q000150:complications / Q000209:etiology* / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D003711:Demyelinating Diseases / Q000150:complications / Q000209:etiology* / Q000235:genetics; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009103:Multiple Sclerosis / Q000209:etiology / Q000378:metabolism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D017421:Sequence Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002868:Chromosomal Proteins, Non-Histone; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human; C110546:TYROBP protein, human; D004259:DNA-Directed DNA Polymerase; C118146:TENT4A protein, human