In my school biology lessons, we studied the causes of genetic mutations and a few diseases that can arise as a result. From the I have researched more into one disease specifically, Huntington's.
Huntington's disease (HD) is a progressive brain disorder that results in the death of brain cells. The part of the brain most affected is a group of nerve cells at the base of the brain known as the basal ganglia. This part of the brain organises muscle-driven movements of the body also known as the motor movements. Adult-onset HD is the most common form of this disorder and usually appears in a person's 30s – 40s. Early symptoms include irritability, depression, small involuntary movements, poor coordination and trouble learning new information or making decisions. As HD progresses the jerking and twitching movements called chorea to become more pronounced. The average life expectancy of adult-onset HD is 15-20 years after initial symptoms.
Huntington's disease is caused by a mutation in the HTT gene on chromosome 4. This gene provides instructions to make a protein called huntingtin. The exact role of this protein is unknown, however, it appears to be involved in an important role in neurons and is essentials for brain development in foetuses. Huntingtin is found in many body tissues, most commonly in the brain. Within cells it may be involved in chemical signalling, transporting materials. Binding to proteins and other structures. It may also protect the cell from apoptosis (self-destruction). Huntington's disease is a trinucleotide disorder because the mutation of the gene occurs in a particular region known as the CAG trinucleotide repeat. This region is made up of CAG base nucleotides that appear multiple times in a row. Normally the CAG triplet is repeated 10-35 times within the region. People with HD have a mutation that increases the size of the CAG trinucleotide repeat resulting in 36-120 CAG repeats. If over 40 repeats occur in the repeat then the person almost always develops HD however people with 36-39 repeats may or may not develop the symptoms of HD. The expanded CAG region leads to the production of an abnormally long huntingtin protein in protein synthesis. The elongated protein is cut into smaller, toxic fragments which bind together and accumulate in nerve cells affecting their normal function. It particularly affects the striatum and cerebral cortex resulting in the symptoms of HD.
HD is inherited by an autosomal dominant pattern meaning that one copy of the mutated gene is enough to pass the disease onto offspring. The size of the CAG trinucleotide repeat often increases as it is passed down generations a process known as anticipation. Anticipation occurs during meiosis for sexual reproduction. Unstable repeats undergo triplet expansion causing germ cells to have a greater number of repeats than somatic cells. Triplet expansion is caused by slippage during DNA replication also called ‘copy choice' DNA replication. The DNA sequence has a repetitive nature which causes ‘loop out' structures to form while keeping the complementary base pairing between the parent and daughter DNA strand. If the ‘loop out' structure is formed on the daughter strand it will cause an increase in the number of repeats. If formed on the parent strand a decrease in the number of repeats is caused. Expansion of these repeats is much more common than reduction so it is more likely that the offspring of a person with HD will have it.
A large number of repeats is associated with early onset HD (more than 60 repeats) which usually appears in childhood or adolescence. People with 27 to 35 repeats in the HTT gene do not have HD but are at risk of having a child with the disease as the CAG triplet will repeat even more for the offspring.
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