title: No common founder for C9orf72 expansion mutation in Sweden.
abstract: Hexanucleotide expansion mutations in the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic cause for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). SNP haplotype analyses have suggested that all C9orf72 expansion mutations originate from a common founder. However, not all C9orf72 expansion mutation carriers have the same haplotype. To investigate if the C9orf72 expansion mutation carriers in Sweden share a common founder, we have genotyped SNPs flanking the C9orf72 expansion mutation in cases with FTD, FTD-ALS or ALS to perform haplotype analysis. We have genotyped 57 SNPs in 232 cases of which 45 carried the C9orf72 expansion mutation. Two risk haplotypes consisting of 31 SNPs, spanning 131 kbp, were found to be significantly associated with the mutation. In summary, haplotype analysis on Swedish C9orf72 expansion mutation carriers indicates that the C9orf72 expansion mutation arose on at least two risk haplotypes.
authors.affiliation: Department of NVS, Division for Neurogeriatrics, Karolinska Institutet, Center for Alzheimer Research, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital, Genetics unit, Stockholm, Sweden.
authors.forename: Huei-Hsin
authors.initials: HH
authors.lastname: Chiang
authors.affiliation: Department of NVS, Division for Neurogeriatrics, Karolinska Institutet, Center for Alzheimer Research, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital, Genetics unit, Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Forsell
authors.affiliation: Department of NVS, Division for Neurogeriatrics, Karolinska Institutet, Center for Alzheimer Research, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital, Genetics unit, Stockholm, Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Lindström
authors.affiliation: Department of NVS, Division for Neurogeriatrics, Karolinska Institutet, Center for Alzheimer Research, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital, Genetics unit, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Lilius
authors.affiliation: Department of NVS, Division for Neurogeriatrics, Karolinska Institutet, Center for Alzheimer Research, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital, Genetics unit, Stockholm, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Thonberg
authors.affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Nennesmo
authors.affiliation: Department of NVS, Division for Neurogeriatrics, Karolinska Institutet, Center for Alzheimer Research, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital, Genetics unit, Stockholm, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D013548:Sweden
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins