WF Blue Project

WF Blue Members

Nina and Isabella!

Project Overview

Tay Sachs is a genetic disorder due to the inheritance of two autosomal recessive alleles. It results in the degeneration of mental and physical capacities, starting at 6 months of age and usually leading to death by four years of age. Tay Sachs is due to a chromosomal mutation in the HEXA gene of chromosome 15, a common mutation is the product of a 4 base pair insertion in exon 11. Prior studies have been done in mice and humans exhibiting Duchenne muscular dystrophy in which oligonucleotide sequences bind to an exon, inducing exon-skipping when splicing occurs. This exon skipping restores the original reading frame and helps to counteract the original mutation effects. Such a system of oligonucleotide induced exon-skipping could also aid in restoring the original reading frame in certain Tay Sachs mutations.

Background Information

The major defect in Ashkenazi Jews with Tay-Sachs disease is an insertion in the gene for the alpha-chain of beta-hexosaminidase. Myerowitz, et al., 1988

This paper describes how a common mutation in Tay-Sachs is a 4 base pair insertion in exon 11 that results in a splice junction defect and pre-mature termination of beta-hexosaminidase.

Oligonucleotide treatment for DMD:

http://www.ncbi.nlm.nih.gov/pubmed/16285002

http://www.sciencedirect.com/science/article/pii/S0140673611607563