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Frequently Asked Questions (FAQ) - Genetic background -

Genetic background

Chromosomes contain genes, which are the basic units of inheritance. A gene is a sequence of DNA (deoxyribonucleic acid) which codes for a certain protein. The DNA is a polymer (long chain) composed of nucleotides whose structure is a double helix. A nucleotide is a chemical compound consisting of a DNA base (adenine, guanine, cytosine or thymine) linked to a sugar molecule (deoxyribose) and a phosphate group. The DNA carries the genetic information, which is translated into specific amino acid sequences within the proteins using the “genetic code”.

Humans are diploid. This means that they have two copies (also called alleles) of each gene, one inherited from each parent. A human cell contains 23 pairs of chromosomes. In each pair, one chromosome comes from the father and the other from the mother.

HD is an inherited genetic (hereditary) disease which is caused by mutations in one gene (the HD gene) present in all cells of the body since fertilisation. This means that HD can be passed on from one generation to the next.

HD is an autosomal genetic disease. This means that it may affect both men and women equally because the abnormal gene is located on a chromosome which is the same in both sexes (autosome or non-sex chromosome).

Most HD affected people are heterozygous. This means that they have two different copies of the gene: one normal copy from the unaffected parent and one abnormal copy from the affected parent. In exceptional cases, when both parents are affected, the offspring may inherit two abnormal copies of the gene (one from each parent). In this case, the child is homozygous (two identical copies of the gene).

HD is a dominant genetic disease. This means that only one abnormal gene copy from either parent is sufficient to inherit the disease. In other words, the mutation in the HD gene dominates over the normal copy from the unaffected parent.

In 1993, scientists identified the gene that causes HD. Located on chromosome 4, this gene codes for a protein called huntingtin (Htt). In the first part of the HD gene, there is a sequence of three nucleotides, cytosine-adenine-guanine (CAG), which is repeated several times (i.e. …CAG-CAG-CAG-CAG…). This is called a “trinucleotide repeat”. According to the genetic code, the trinucleotide CAG codes for the amino acid glutamine. Hence, a sequence of CAG repeats forms a chain of glutamines or “polyglutamine”.

A trinucleotide repeat length of up to 35 CAG units is considered normal. When the HD gene has more than 40 CAG repeats, the altered form of the huntingtin protein produced will cause the disease within a normal life time. Hence, HD is caused by a trinucleotide repeat expansion and is one of several polyglutamine diseases.