No evidence for shared etiology in two demyelinative disorders, MS and PLOSL.
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.
Sulonen
Anna-Maija
AM
Finnish Institute for Molecular Medicine, FIMM, and National Public Health Institute, Biomedicum, Helsinki, Finland.
Kallio
Suvi P
SP
Ellonen
Pekka
P
Suvela
Minna
M
Elovaara
Irina
I
Koivisto
Keijo
K
Pirttilä
Tuula
T
Reunanen
Mauri
M
Tienari
Pentti J
PJ
Palotie
Aarno
A
Peltonen
Leena
L
Saarela
Janna
J
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
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