View Full Version : Huntington's Disease and PolyGlutamine Repeats

08-04-2012, 05:06 PM
Huntington's disease is a neurodegenerative disease that mostly affects people of West European descent. It is caused by defects in the gene coding for the "Huntingtin" protein. People with or at risk of Huntington's disease carry an excessive number of CAG repeats (coding for the amino acid glutamine), which causes the production of a defective Huntingtin protein that eventually leads to neuronal apoptosis (programmed cell-death).

A person is likely to develop the disease if he or she has 36 or more CAG repeats. The risk of disease and severity of symptoms increase with the number of repeats. It's very rare for someone to develop the disease without inheriting 36 or more repeats from a parent (meaning the mutation would have happened in utero or in the gonads). Those with 36-40 repeats are at risk, but will usually be affected by the disease. Those with greater than 40 repeats always develop the disease.

A table for age of onset for CAG repeats 39 and greater: http://www.compgene.com/hd.htm

Get tested (Columbia Medical Center in NYC - 23andme cannot test repeats): http://www.hdny.org/genetic.html

08-04-2012, 08:35 PM
Some more information on Huntington's from Clinical Medicine 4th Ed;

Huntington's disease is a rare autosomal dominant condition with full penetrance. Expansion of CAG repeats in the Huntington's disease gene on chromosome 4 leads to production of a mutant huntingtin protein. It is not known how the mutant protein causes disease. There is loss of neurones within the basal ganglia, leading to depletion of GABA and acetylcholine but sparing dopamine. Symptoms begin in middle age and there is then a relentlessly progressive course, with chorea and personality change preceding dementia and death. No treatment arrests the disease, and the management is symptomatic treatment of chorea and genetic counselling of family members.

Chorea is defined as "a continuous flow of jerky, quasi-purposive movements, flitting from one part of the body to another."

Little bit
09-29-2012, 03:24 PM
Interesting tid-bit about Huntington's Disease:

Huntington’s Gene Mutation Carriers Learn Faster

The worse the mutation, the better the learning efficacy. Seems to boil down to glutamate:

Degenerative diseases of the nervous system are based on complex changes. A key mechanism is an increased release of the neurotransmitter glutamate. However, since glutamate is also important for learning, in some cases it could lead to the paradoxical effect: better learning efficiency despite degeneration of the nerve cells.

Exceptional intelligence has been linked with schizophrenia and bipolar, connected to genetic risk for genetic diseases such as with Ashkenazi Jews, and now Huntington's Disease. Autism researcher, Baron-Cohen hypothesizes that autism could be the unintended consequence of brainy systemizer's getting together. So is exceptional intelligence actually a genetic liability, and not a gift?

10-02-2012, 06:21 AM
Little bit, thank you for sharing. It may also interest you that melatonin (or lack thereof) also appears to play some role in some cases of autism. Google about acetylserotonin O-methyltransferase (ASMT; present on both X and Y chromsomes in pseudoautosomal region) and autism.
...sorry for the tangent

Little bit
10-02-2012, 12:19 PM
Interesting, thanks Human. Doesn't appear that I can check our 23andme raw data for any ASMT variants but I did find this paper:

My son takes Melatonin often and I know many ASDer's take it every night. I would not be surprised at all if Melatonin plays a significant role in autism due to how prevalent sleep issues are for them. I also have sleep issues but mine seems different: whereas my son, and his ASD cousin have significant difficulty falling asleep...I fall asleep easily, but wake up and then can't go back to sleep. I've had this problem with sleep all my life so I'm inclined to believe it very well could be something genetic.