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By Larisa Mihali
Neurogenetics is a scientific field that merges the study of the brain with the principles of genetics. Many autoimmune diseases including Alzheimer's disease, ALS, Huntington’s disease, and others have genetic underpinnings. What if scientists could figure out which genetic factors are responsible for their illness?
Neurogenetics is a field of scientific research that uses recent advances in genome sequencing in order to better understand the cause of brain and nerve disorders. Neurogenetics also helps advance the concept of personalized clinical care. With a comprehensive understanding of a patient’s genetic profile and medical history, physicians can create highly tailored treatment programs for each patient. For example, a cancer patient can now receive genome analysis of the specific mutations within a tumor. Based on those results, doctors can then assess whether cancer medications (which can be highly toxic) will even work before administering the drug.
How has neurogenetics developed as a field of medicine? The Human Genome Project—a global effort to map each gene in the human body—represented a major breakthrough when it was completed in 2003. Then, scientists developed whole exome sequencing, which looks just at the small portion of DNA that is usually responsible for genetic diseases, which made the tool more affordable and practical.
The two founders of the field of neurogenetics, Seymour Benzer and Sydney Brenner, recognized more than half a century ago the power to use the tools of the microbial genetics trade, in which Benzer and Brenner were so well versed, to the question of how the nervous system develops and functions. Forward genetic screens and later reverse genetic approaches have firmly established the power of genetics in revealing fundamental insights into the brain. With the advancement of technological tools, we are able to understand with increased resolution the composition of the nervous system and construct atlases, from comprehensive molecular composition of diverse neuronal and glial types to activity maps of single neurons/ensembles, to complete connectomes of the nervous system.
Today, researchers can study the DNA of hundreds of patients with a given condition to search for patterns that may exist in their genomes. Thanks to those and other advancements, the field of neurogenetics has already successfully identified genes related to the development of Alzheimer’s, Parkinson’s, Huntington’s, and Multiple Sclerosis.
Let’s look a little bit more into these neurological diseases. Alzheimer disease (AD) is the fourth leading cause of death in adults. The incidence of the disease rises steeply with age. AD is twice as common in women than in men. Some of the most frequently observed symptoms of the disease include a progressive inability to remember facts and events and, later, to recognize friends and family.
AD tends to run in families. Currently, mutations in four genes, situated on chromosomes 1, 14, 19, and 21, are believed to play a role in the disease. The formation of lesions made of fragmented brain cells surrounded by amyloid-family proteins are characteristic of the disease. Tangles of filaments largely made up of a protein associated with the cytoskeleton have also been observed in samples taken from Alzheimer brain tissue.
Currently, scientists are studying the interrelationship between the various gene loci (particularly the mutation on chromosome 21) and how environmental factors could affect a person's susceptibility to AD. Recently, use of a mouse model of the disease identified an enzyme that may be responsible for the increase in amyloid production characteristic of AD. If a way to regulate this enzyme could be found, then AD may be slowed or halted in some people.
Huntington disease (HD) is an inherited, degenerative neurological disease that leads to dementia. The HD gene, whose mutation results in Huntington disease, was mapped to chromosome 4 in 1983 and cloned in 1993. The mutation is a characteristic expansion of a nucleotide triplet repeat in the DNA that codes for the protein huntingtin. As the number of repeated triplets - CAG (cytosine, adenine, guanine) - increases, the age of onset in the patient decreases. Furthermore, because the unstable trinucleotide repeat can lengthen when passed from parent to child, the age of onset can decrease from one generation to the next. Since people who have those repeats always suffer from Huntington's disease, it suggests that the mutation causes a gain-of-function, in which the mRNA or protein takes on a new property or is expressed inappropriately.
With the discovery of the HD gene, a new predictive test was developed that allows those at risk to find out whether or not they will develop the disease. Animal models have also been developed, and we know that mice have a gene that is similar to the human HD gene. Research on understanding the mechanism that causes the triplet repeat to increase is ongoing, since its discovery could be critical to the development of an effective treatment for this and other similar diseases.
In conclusion, neuroscience and genetics are both fascinating immense fields that are continuously improving regarding diagnostics and treatments. Please keep in mind that these few diseases referenced in this article are not 100% inherited through genes, they can be discovered even if it is not handed down by ascendants; but if one of these runs in families for a few generations then the chances may be higher for some.
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