Cathepsin D: screening for new polymorphisms using single-strand conformation polymorphism analysis.
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.
Majores
Micael
M
Department of Psychiatry, University of Bonn, D-53105 Bonn, Germany.
Kolsch
Heike
H
Bagli
Metin
M
Papassotiropoulos
Andreas
A
Lohmann
Petra Louise
PL
Schmitz
Sandra
S
Rao
Marie Luise
ML
Maier
Wolfgang
W
Heun
Reinhard
R
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
D002402:Cathepsin D