Thursday, October 30, 2014

Identification of a Gene Associated with Familial ALS

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gherig's disease, is a fatal, "progressive, neurodegenerative disorder affecting the motor neurons in the central nervous system." As the motor neurons die, the brain loses its ability to communicate signals to the body's muscles, ultimately resulting in loss of voluntary muscle movement, paralysis, and eventual respiratory failure. According to the ALS association, the disorder affects 6-8 out of 100,000 people, and 10% of the cases are inherited. There is no cure for the disorder, and the cause of most cases is unknown.

A team of international scientists at the University of Massachusetts Medical School used exome sequencing in order to determine possible genes associated with familial ALS. This technique entails sequencing only the protein-coding genes in a genome. The team performed an exome-wide screen on 363 people with famililar ALS. Each subject also had a relative with the disorder. The team analyzed every coding gene in the genome of the subjects, specifically looking for patterns of rare, damaging mutations that are found more frequently in subjects with ALS.

Through their analysis, the team recognized an elevated frequency of  mutation in the TUBA4A gene in subjects with ALS. The team performed further analyses and was able to determine that the TUBA4A gene is associated with familial ALS. TUBA4A encodes for the protein Tubulin Alpha 4A.
Although the highest levels of the protein occur in the brain, the protein can be found in all human tissue. TUBA4A protein plays a vital role in the nerve cell. The protein "helps build the microtubule network, one of the most important structural components of the nerve cell" by moving the vital building blocks. The team found that mutated TUBA4A protein "is toxic to the neuron by weakening the entire microtubule network.

Landers, PhD, states that "identifying even rare mutations that could cause ALS" is of great importance as these mutations may lead to other common pathways that are changed before motor neuron death in ALS. The study also supports the idea that the cytoskeleton architecture and dynamics are crucial in the progression of ALS.

I was immediately drawn to this article after being bombarded by "Ice Bucket Challenges" all summer. Overall, I think it is really exciting that the TUBA4A was identified to be associated with familial ALS. Any advancements in this disorder are of great value to the scientific community as there is little knowledge regarding the disorder. Hopefully, with all of the donations and increased awareness of ALS, more studies like the one outlined in this article can be performed to gain more knowledge of the genetic roots of the disease.

Article: http://www.medicalnewstoday.com/releases/284333.php
Related Article:
http://ac.els-cdn.com/S0896627310009785/1-s2.0-S0896627310009785-main.pdf?_tid=469435f8-6079-11e4-a282-00000aacb362&acdnat=1414703652_490b044105d452aeb30b16b2123d7470

No comments:

Post a Comment