WF Blue Project

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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.

Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide Fletcher, et al., 2005

Studies were performed on mdx mice, or mice exhibiting a nonsense mutation in exon 23 of the dystrophin gene. Antisense oligonulceotides were administered to the mice, along with 2-O-methylphosphorothioate and peptide nucleic acid

Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study Cirak, et al., 2011

Through this study patients with DMD were treated using oligonucleotides. This study showed an increase in dystrophin levels.

Project Details and Methods

Predicted Outcomes

Resources Required