title: Cathepsin D: screening for new polymorphisms using single-strand conformation polymorphism analysis.
abstract: Cathepsin D (CTSD) is a lysosomal protease involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer's disease (AD). Previous findings revealed a significant association between the T allele of the 224 C/T (A58V) polymorphism in exon 2 of the CTSD gene and late onset AD. The exonic regions of the CTSD gene were screened for further polymorphic variations using polymerase chain reaction and single-strand conformation polymorphism analysis. In addition to the known 224 C/T polymorphism and two silent mutations in exons 3 and 4 we detected two new polymorphisms in introns 5 and 8. Combination of these sequence variations results in three different haplotypes; one of these haplotypes is due to the new polymorphism in intron 5. We detected no further missense mutations except for the known 224 C/T polymorphism in exon 2. Thus, if sequence variations within the CTSD gene influence the risk for various diseases, the pathogenic mechanism is likely to be linked to the amino acid substitution in the profragment of CTSD.
authors.affiliation: Department of Psychiatry, University of Bonn, D-53105 Bonn, Germany.
authors.forename: Micael
authors.initials: M
authors.lastname: Majores
authors.forename: Heike
authors.initials: H
authors.lastname: Kolsch
authors.forename: Metin
authors.initials: M
authors.lastname: Bagli
authors.forename: Andreas
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: Petra Louise
authors.initials: PL
authors.lastname: Lohmann
authors.forename: Sandra
authors.initials: S
authors.lastname: Schmitz
authors.forename: Marie Luise
authors.initials: ML
authors.lastname: Rao
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Reinhard
authors.initials: R
authors.lastname: Heun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D002402:Cathepsin D / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D002402:Cathepsin D