Introduction
Huntington’s disease (HD) is an inheritable disease that causes progressive nerve degeneration in the brain; its development largely requires an individual to have a genetic predisposition. The disease, which affects the ability to move and patterns of thinking, can lead to various psychiatric diseases. Despite familiarity with the symptoms and progression of this malady, the exact processes behind the predisposition toward and development of Huntington’s disease are unknown. At the present time, the most prominent theory states that HD is influenced by single nucleotide polymorphisms (SNPs) found in specific haplogroups. The purpose of this paper is to discuss the genetic factors affecting the development and progression of HD.
Discussion
The articles reviewed in the scope of this paper indicate that haplogroups alone are too broad a topic to satisfactorily explain the development and progression of HD. Lee et al. (442) argue that 82% of all HD chromosomes are found in the 7 most widespread haplogroups, which does not correlate with the presence of the disease. This means that while the predisposition toward HD is wide, only relatively few individuals inherit and develop HD, indicating that a different part of the genome is involved.
However, the haplotype theory states that specific SNPs are responsible for the modulation of HD in patients. Diego-Balaguer et al. (5) find that COMT Val158Met polymorphism modulates disease progression, either by affecting the patient’s resilience or by decreasing performance in the later stages of the disease. Finally, Warby et al. (351) claim that CAG expansion has a direct correlation on both predisposition and development of HD, with the risks increasing past 36 CAG.
Based on this information, it could be hypothesized that haplotypes affect CAG expansions, in turn making individuals more or less likely to develop HD. However, haplotypes do not expand all or even the majority of cases of HD development; in other words, they can modulate the progression but not the development of the disease. The results of these researches are important in that they help guide the direction of further research into the genome as it relates to HD.
Together, they show that haplogroups are important but not the defining feature in HD inheritance and progression. Collectively, they suggest that the main defining features of HD should be sought in other genomic formations.