A Darwinian approach to Huntington's disease: subtle health benefits of a neurological disorder.

  title={A Darwinian approach to Huntington's disease: subtle health benefits of a neurological disorder.},
  author={Benjamin R Eskenazi and Noah Wilson-Rich and Philip T B Starks},
  journal={Medical hypotheses},
  volume={69 6},
Antagonistic pleiotropy in mice carrying a CAG repeat expansion in the range causing Huntington’s disease
This novel mouse line provides direct experimental evidence that, although the HD mutation causes a fatal neurodegenerative disorder, there may be premorbid benefits of carrying the mutation.
Genetic counseling and testing for Huntington's disease: A historical review
  • M. Nance
  • Medicine
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2017
How the emergence of Huntington's disease registries and patient support organizations, genetic testing, and the discovery of a disease‐causing CAG repeat expansion changed the contours of genetic counseling for families with HD are reviewed.
Comment on Eskenazi et al.
  • R. Albin
  • Medicine, Biology
    Medical hypotheses
  • 2008
Antagonistic Pleiotropy in Human Disease
The strength of evidence for antagonistic pleiotropy in humans is examined and a primer of evolutionary theory on types of selection as a guide for understanding this mechanism and how it may manifest in other diseases is provided.
Antagonistic pleiotropy as a widespread mechanism for the maintenance of polymorphic disease alleles
It is hypothesized that, rather than being an exception to the rule of genetic disorders, antagonistic pleiotropy may be common and this may explain why so many serious diseases, even apparently environmentally caused ones, have a genetic component.
Antagonistic pleiotropy and mutation accumulation influence human senescence and disease
The predictions of two evolutionary explanations of senescence—mutation accumulation and antagonistic pleiotropy—which postulate that genetic variants with harmful effects in old ages can be tolerated, or even favoured, by natural selection at early ages are tested.
Possible Role of the Polyglutamine Elongation in Evolution of Amyloid-Related Evolvability
The objective of this paper is to determine whether evolvability could also be applied to the physiological functions of epolyQ, which is widely expressed from microorganisms to human brain, whereas APs are only identified in vertebrates.
3-Nitropropionic Acid as a Tool to Study the Mechanisms Involved in Huntington’s Disease: Past, Present and Future
This review will focus on the past and present research of 3-Nitropropionic acid, to finally bring a perspective on what will be next in this promising field of study.
Caracterizaçāo das citocinas na doença de Machado Joseph
Levels of eotaxin, a peptide secreted by astrocytes, were elevated in the asympt omatic carriers, suggesting that a specific response of these cells can be related to symptom p r gression, in SCA3/MJD.


Genetic fitness in Huntington's Disease and Spinocerebellar Ataxia 1: a population genetics model for CAG repeat expansions
An analysis of genetic fitness was performed in Huntington's Disease (HD) and Spinocerebellar Ataxia 1 (SCA1) families and a model based on a differential fitness according to the degree of expansion predicted the frequency of alleles in the low/medium range has been maintained or even increased up to relatively recently.
Huntington's disease
Instability of CAG repeats in Huntington's disease: relation to parental transmission and age of onset.
Several features of the expansion mutation in HD are similar to those previously observed for mutations of similar size in spinobulbar muscular atrophy and in myotonic dystrophy, and to those observed more recently in spinocerebellar ataxia type 1 and in dentatorubropallidoluysian atrophy, four diseases also caused by expansion of CAG repeats.
Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects
The existence of an intermediate allele in parental alleles of 30–38 CAG repeats in the HD gene which is greater than usually seen in the general population but below the range seen in patients with HD is shown.
Structure and expression of the Huntington's disease gene: Evidence against simple inactivation due to an expanded CAG repeat
Observations suggest that the dominant HD mutation either confers a new property on the mRNA or alters an interaction at the protein level, suggesting the operation of interacting factors in determining specificity of cell loss.
Recent insights into the molecular pathogenesis of Huntington disease.
In a YAC transgenic mouse model that replicates key elements of the HD phenotype, the development of selective striatal neurodegeneration is coincident with cleavage of htt and translocation of the N-terminal htt fragment into the nucleus, and inhibition of this process may be a potential therapeutic strategy for this currently untreatable disorder.
Mutational bias provides a model for the evolution of Huntington's disease and predicts a general increase in disease prevalence
This work finds that human alleles have expanded from a shorter ancestral state and exhibit unusual asymmetric length distributions, and predicts an ever–increasing incidence of Huntington's disease.
Huntington’s disease
The rate of progression of HD was significantly more rapid with a younger age at onset, and CAG repeat length may be an important determinant of not only the age of onset, but also the rate of disease progression.
Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells.
These phenotypes indicate a disruption of striatal cell homeostasis by the mutant protein, via a mechanism that is separate from its normal activity, and support specific stress pathways, including elevated p53, endoplasmic reticulum stress response and hypoxia, as potential players in HD.