12. The search for the genetic lesion in Ashkenazi Jews with classic Tay-Sachs disease

Abstract

Publisher Summary This chapter gives an overview on the search for the genetic lesion in Askenazi Jews with Classic Tay-Sachs diseases (TSD). Elucidation of the mutation underlying classic TSD in the Ashkenazi Jewish population posed more of a challenge. Restriction enzyme digestion patterns of the mutant α-chain gene were identical to those of the normal gene, indicating that the mutation involved a small deletion or single base change. Amplification of the region encompassing the mutation by polymerase chain reaction followed by digestion of the amplified product with Dde1, then Southern analysis of the sample, reveals a 120-base-pair DNA (deoxyribonucleic acid) fragment from the normal allele in contrast to an 85-base pair piece from the mutant. It has generally been assumed that only one mutation gives rise to the classic form of TSD in the Ashkenazi Jewish population. PCR-based assay for the insertion mutation which involved amplification of a segment of exon 11 inclusive of the region of insertion and detection of the lesion by probing duplicate samples of the amplified product with oligonucleotides specific for either the normal or mutant sequence was developed.