A thorough assessment of benign genetic variability in GRN and MAPT.
Mutations in APP, PSEN1, MAPTand GRNare the most common genetic causes of dementia. The previous miss-assignment of pathogenicity to benign variants in these genes stresses the importance of discerning between disease causing mutations and benign variants with no pathogenic effect on the function of the respective protein. In this study we sequenced GRNand MAPTin 282 samples from the Centre d'Etude du Polymorphisme Humain - Human Genome Diversity Cell Line Panel, in order to identify benign variants that could otherwise be mistaken for pathogenic mutations. We found sixteen different non-synonymous changes, eleven of which are novel variants.
Guerreiro
Rita J
RJ
Laboratory of Neurogenetics, National Institute of Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. portalegrer@nia.nih.gov
Washecka
Nicole
N
Hardy
John
J
Singleton
Andrew
A
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D005091:Exons / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D000077153:Progranulins; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics*
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D016875:tau Proteins