A thorough assessment of benign genetic variability in GRN and MAPT

Hum Mutat. 2010 Feb;31(2):E1126-40. doi: 10.1002/humu.21152.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Exons / genetics
  • Genetic Variation*
  • Humans
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Molecular Sequence Data
  • Open Reading Frames / genetics
  • Progranulins
  • Protein Structure, Tertiary
  • Sequence Alignment
  • tau Proteins / chemistry
  • tau Proteins / genetics*

Substances

  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • MAPT protein, human
  • Progranulins
  • tau Proteins