Neurogenetics - An Overview

Introduction:

Many autoimmune disorders such as Alzheimer's disease (a type of brain disorder, which slowly causes memory loss, and destroys thinking skills including simple tasks), amyotrophic lateral sclerosis (ALS, a neurological disorder that affects nerves involved in voluntary muscle movements), multiple sclerosis (a disease in which the immune system attacks the myelin sheath that covers the nerves), Huntington's disease (neurological disease, where the nerves breakdown), myotonic muscular dystrophy (a disease which causes gradual loss of muscle and its weakness), Charcot-marie-tooth (CMT, degenerative disease, which causes muscle weakness, decreased sensation and other symptoms) neuropathy, and Friedreich ataxia (a disease that affects the nerves) are related to genetic factors and mutations such as trinucleotide repeat expansions, duplication, and deletion in genes. The Human Genome Project is the greatest project which contains the entire human genome (complete set of DNA which is present in the cell). Neurogenetics can help in understanding the cause of brain disorders with the help of whole genome sequencing and identifying the genes which can help in treatment approaches.

What Is Neurogenetics?

Neurogenetics is the study of genetics which helps in analyzing the effects of genes on the function and structure of the brain and nervous system. Neurogenetics can help in identifying the genes underlying the diseases of the brain and identifying risk factors associated with those conditions. Neurogenetics can also help in identifying genes associated with positive personality traits, such as intellect or athletic ability, and negative personality traits, such as anger or violence.

What Are The Uses Of Neurogenetics?

The uses of neurogenetics are:

• Neurogenetics Can Help in Finding Diagnostic Markers: Genetics has a role in neurological diseases. Diseases are related to a region on the chromosome, and some may be due to mutations, such as in Huntington's disease. Some mutations can cause an increased risk of disease but cannot directly cause the disease, such as the APOE4 gene in Alzheimer's disease. Some genes contribute to the disease phenotype, such as Parkinson's disease (a brain disorder that causes uncontrollable movements), muscular dystrophy, amyotrophic lateral sclerosis, and many forms of epilepsy. As genetic determinants are being explored, distinct forms of neurological and psychiatric diseases that can disappear or fade, such as depression or Parkinson's disease, have the same determinants seen in bipolar disorder. The Genetics of some neurological disorders are:

  1. Huntington's Disease: It is a neurodegenerative inherited disorder where the nerve cells present in the brain slowly break down. This occurs due to a mutation in the gene called huntingtin, this mutation can cause CAG (nucleotide bases in DNA) to repeat, and more than 36 CAG repeats can develop this disease, and these people have a 50 percent of chance to pass down the condition to the offspring. Genetic testing can be done to determine the chance of passing down the disease; the most effective test is a direct genetic test, which counts the number of CAG repeats.

  2. Autism: It is a neurodevelopmental genetic disorder. This disease is associated with many genes, and there is no single gene that causes this disorder. The concordance rate between identical twins is high. This requires early diagnosis, which can be difficult due to delays in verbal IQ (intelligence quotient) and language; other measures, such as tracking eye movements and estimation of brain volume, obtained by non-invasive Magnetic Resonance Imaging (MRI) can be helpful. Infants who have older siblings with autism are focused highly because siblings are more affected. There are several forms of autism. The classical form includes deficits in language development, social cognition, and repetitive, restrictive movements. Genetic testing for this condition is not yet reliable, but recently the copy number variants can cause genetic mutations. Children who are affected by Fragile X syndrome or Rett Syndrome (a developmental disorder of the brain) commonly exhibit autism. Early intervention with behavioral therapy can be effective.

  3. Alzheimer's Disease: It is a type of brain disorder, which slowly causes memory loss, and destroys thinking skills, including simple tasks. There are two types, early onset or familial Alzheimer's disease and late-onset. Early onset occurs between 45 and 60 years of age, and this is strongly related to family history. It is an inherited autosomal dominant disorder in which mutation in the amyloid beta gene occurs, and fragments of AB42 protein accumulate throughout the brain. Plaques in the frontal lobe and hippocampus are related to loss of memory and learning ability. Late onset of Alzheimer's disease occurs after 65 years, and an allele of the apolipoprotein E (APOE) gene, located on chromosome 19, is the strongest risk factor associated with this disorder.

  4. Epilepsy: It is a neurological disorder characterized by seizures (uncontrolled electrical activity of the brain that affects movements, consciousness, feelings, and behavior), unusual behavior, or loss of awareness. This occurs due to genes that regulate the components of membrane ion channels and cause neuronal excitability.

• Neurogenetics Can Help in Genetic Testing: Genetic testing can help in studying DNA (deoxyribonucleic acid) and its variations. Types of genetic testing are:

  1. Genetic Testing of Minors: Minors (below eighteen) who are at risk of developing genetic disorders because of family history. For example, in the case of Lesch-Nyhan Syndrome, which is an inherited violent self-destructive disorder, genetic tests can distinguish it from others and help in therapy and predicting prognosis.

  2. Prenatal Testing and Pre-implantation Genetic Diagnosis: Couples undergoing in vitro fertilization (IVF) who has a family history of risk of developing neurological disorders can help in relieving genetic information.

Genetic tests can be done with the help of trained geneticists and genetic counselors, along with the help of family history. The use of whole genomic sequencing has made genetic testing less expensive but more complex. A specialized test called Chromosomal microarray testing is done to detect duplicated or deleted regions on DNA.

• Use of Neurogenetics in Therapeutic Management: The use of approaches such as RNA (ribonucleic acid) silencing, Gene replacement, and stem cells help in therapeutics. Replacing abnormal protein with normal protein can help in the management of muscular dystrophy. RNA silencing is interfering with the RNA, which is caused by the mutated gene and therefore hindering its function.

• Behavioral Use of Neurogenetics: It is a new scientific approach in which researchers are finding whether genes are responsible for behaviors such as intelligence, learning ability, athletic ability, and many more skills. But personality and behavioral traits can be self-molding and an adjustment to the environment despite genetic predisposition.

• Other Uses:

  1. Neurogenetics can help in understanding new genes, mechanisms of diseases, and their pathogenesis.

  2. Neurogenetics helps in understanding variable disease phenotypes.

Conclusion:

Interpreting the genetic test results can be a challenging task even for a skilled person and depends on varying knowledge of disease susceptibility. According to studies, genes have a complex network rather than being simple. Predicting the disease outcome is difficult, especially if environmental factors are included.