By: Heala, Stephanie and Megan

Where is the gene located (chromosome number, gene locus)?

  • Tay-Sachs disease results from defects in a gene on chromosome number 15 that codes for the production of the enzyme beta-hexosaminidase A, also known as Hex-A (National Centre for Biotechnology Information, 2015).

What type of mutation causes the disorder?

  • Tay-Sachs is an autosomal recessive disorder, the disorder results from mutations in the gene encoding the alpha-subunit of beta-hexosaminidase A. (Learning About Tay Sachs Disease, 2015).
  • Seventy-eight mutations in the Hex A gene have been discovered and this includes sixty-five single base substitutions, eleven deletions and two insertions (NTSAD- Causes, 2015).
  • An example of the insertion is the four base insertion (TATC) in exon 11, which results in an altered reading frame for the Hex A (HEXA) gene, thus resulting in an early stop codon. (Learning About Tay Sachs Disease, 2015).

Figure 1. The gene on chromosome 15, where the premature stop codon is created.

What is the function of the protein the gene codes for?

  • In this case, the protein acts more like an enzyme, which is Hex A (NTSAD- Causes, 2015).
  • Hex A is a lysosomal enzyme composed of alpha and beta polypeptides, this enzyme aids lysosomes to break down large molecules for recycling (NTSAD- Causes, 2015).
  • In normal conditions, Hex A helps to degrade a lipid called GM2 ganglioside (NTSAD- Causes, 2015).

What effect does the mutation have on the structure of the protein the gene codes for?

  • Mutations in the Hex A gene disrupts the activity of beta-hexosaminidase A, which prevents the enzyme from breaking down GM2 ganglioside (Tay-Sachs disease, 2015).
  • Furthermore, mutations in the DNA changes the sequence of the bases, this leads to the bases in mRNA to be different as well. Resulting change in the sequence of amino acids of proteins, therefore primary structure of protein changes (Tay-Sachs disease, 2015).

What is the mechanism of the disorder (what effects does the alteration in function of the protein have on the workings of the cell and the body)?

  • This mutation occurs when the enzyme is absent or present in very small amounts, resulting in excessive accumulation of GM2 ganglioside in neurons (Goldstein, 2011).
  • Consequently the destruction of these neurons, which causes the signs and symptoms of Tay-Sachs disease (Tay-Sachs Disease, 2015).

Diagram of the wild type and mutated type protein and the pathway.

Figure 2. Tay-Sachs disease inserts 4 base pairs to the Hex A gene, causing change the reading frame. This is a nonsense and misense point mutation (Adnan, 2011).

Figure 3. Tay Sachs affects the lysosomes in the neurons of the brain and spinal cord.

Figure 4. The pathway of genetically inheriting Tay-Sachs, through an example of two parents who are unaffected but carriers, and the chances of their reproduction being affected or unaffected.  

What are the symptoms of the disorder?

  • Deafness
  • Blindness
  • Decreased muscle tone
  • Increased startle response
  • Degenerates the neurons in the brain and spinal cord
  • Paralysis or loss of muscle function
  • Seizures
  • Delayed mental and social developments
  • Low growth rates
  • Red spot on the macula (Herndon, 2012)

Can the disorder be treated? If so, how?

  • There is no cure for Tay-Sachs disease (Herndon, 2012).
  • Treatment may include medication for pain or to control seizures, physical therapy, feeding tubes, and respiratory care to reduce mucus buildup in the lungs (Herndon, 2012).
  • Emotional support for the affected family is also critical in care (Herndon, 2012).


A genetic screening programme for Tay-Sachs disease and cystic fibrosis for Australian Jewish high school students. (n.d.). Retrieved May 17, 2015, from http://jmg.bmj.com/content/40/4/e45.full

Adnan, M. (2011). Genetic Diseases. Retrieved May 18, 2015, from http://medicinembbs.blogspot.ca/2011/02/genetic-d.

Goldstein D. Growth of genome screening needs debate. Nature [serial online]. August 4, 2011;476(7358):27. Available from: Science Reference Center, Ipswich, MA. Accessed May 18, 2015.

Herndon, J. (2012, July 25). Tay-Sachs Disease. Retrieved May 18, 2015, from http://www.healthline.com/health/tay-sachs-diseas...

HEXA gene. (n.d.). Retrieved May 17, 2015, from http://ghr.nlm.nih.gov/gene/HEXA

Learning About Tay-Sachs Disease. (n.d.). Retrieved May 17, 2015, from https://www.genome.gov/10001220

Myerowitz, R., & Costigan, F. (1988). The Major Defect in Ashkenazi Jews with Tay- SachsDisease Is an Insertion in the Gene for the at-Chain of beta-Hexosaminidase. The Journal of Biological Chemistry, 263(35), 18587-18589.

National Centre for Biotechnology Information (US). (n.d.). Retrieved May 17, 2015, from http://www.ncbi.nlm.nih.gov/books/NBK22250/

NTSAD - Causes. (n.d.). Retrieved May 17, 2015, from http://www.ntsad.org/index.php/tay- sachs/causes

Tay-Sachs disease. ( October, 2012). Genetics Home Reference. Retrieved May 18, 2015 from http://ghr.nlm.nih.gov/condition/tay-sachs-disease

Comment Stream

a year ago

Well done ladies! Extensive research, all cited properly, and explained in a clear, concise manner. Great job!