Scott Webster
University of New Hampshire

Tay-Sachs disease (TSD) is a rare, autosomal genetic, lipid storage disease that causes neurological degeneration, usually in infants, resulting in death. Children born with Tay-Sachs die at a very young age, usually by the age of 4. Tay-Sachs is the first documented GM2 gangliosidosis, a family of clinically identical diseases that also includes Sandhoff disease and AB variant. Although TSD was one of the first diseases studied at a molecular and genetic level, there is no cure, or even treatment, for this lethal disease. Fortunately, the disease is very rare, but there is a higher prevalence of the disease in certain populations, mainly the Ashkenazi Jews, French Canadians from Quebec, and Cajuns in southern Louisiana (Sutton, V.R., 2002).
GeneChip Microassay, a modern descendant of techniques discovered by the research of TSD. (Used with permission from Creative Commons Attribution-Share Alike 2.0 Generic)

TSD was first diagnosed over 100 years ago, and, unfortunately, the debilitating and deadly course of the disease is easily observable and well documented. But as our understanding of genetics, molecular biology, and biochemistry has matured, we are no longer forced to simply answer what Tay-Sachs disease is, but are now able to ask many more questions about its cause, origins, and possible treatments. With new studies and technologies, it is now know that the neurological degradation and fatal effects of TSD are caused by an accumulation of gangliosides, but we can also research the normal function of these molecules and the mechanisms behind how they accumulate in TSD affected individuals. We can also explore the reason behind their accumulation and identify the "broken link in the chain," the biochemical difference between normal individuals and those with TSD. With genome mapping and gene sequencing, we can now identify the mutated gene that codes for TSD -- the root cause of the disease. Finally, we can also use genomics and bioinformatics to construct an evolutionary "heritage" of the genetic traits, constructing phylogenetic trees that can help in understanding the disease's origin, spread, and history, much in the same way a family tree helps us understand our family's history while helping us find out who we are, as individuals. If we continue to ask these questions and can answer them, we may be able to one day find a cure for Tay-Sachs disease.

As scientific advancements allow for us to further research Tay-Sachs and other genetic diseases, research on TSD has, in turn, allowed for more scientific advancement. Although a treatment remains elusive, research on Tay-Sachs disease has already yielded results in the form of new genetic screening techniques, molecular diagnostic assays, and the expansion and advancement of molecular biology. As our genomic understanding grows, Tay-Sachs and the GM2 gangliosidoses once again may provide a unique opportunity to advance a field of study. At a genetic/genomics level, TSD poses many questions with its connection to ethnic groups, with an opportunity to explore the possibility of a heterozygous advantage, as well as a chance to look at genetic drift, differential immigration patterns, and the founder effect.

As much as the GM2 gangliosidoses may do for the study of genetics, it may even be possible to find a treatment for the diseases while examining them through a genomics lens. At one point in our history, it was impossible to treat insulin dependent diabetes, until we discovered other animals that produced insulin that was similar to the human type. Before genetic engineering made synthetic human insulin possible, we isolated this vital hormone from other organisms. If it is possible to find species with highly conserved HEXA, HEXB, and GM2A genes, it may be possible to isolate working Hexosaminidase A enzymes and/or GM2 activating protein cofactors from these organisms.

TSD Hexosaminidase A. Image accessed from KEGG ( Licensed for academic use only (Not for commercial use).

Literature Review
1) What is Tay-Sachs disease?
2) What are the clinical symptoms of Tay-Sachs?
3) What are GM2 gangliosides and how do they accumulate??
4) What gene is involved with Tay-Sachs and is it different from the other, clinically identical, GM2 Gangliosidosis diseases? Any known reason for the connection between specific identified mutations and certain populations?
5) What are the affected gene products of the Tay-Sachs gene variant?

Genomic and Proteomic Research and Analysis
6) How does the normal TSD protein function and interact in the body?

7) Are their other organisms that get Tay-Sachs, and that may produce the normal TSD protein?


7) Materials and Methods

8) Works Referenced