Central Idea

The Nizam’s Institute of Medical Sciences in Hyderabad reports three to four cases of Huntington’s disease monthly, with each case impacting entire families.

Understanding Huntington’s Disease

	Details
Nature of Disorder	Genetic, progressive brain disorder
Genetic Cause	Mutation in the huntingtin gene on chromosome 4
Inheritance Pattern	Autosomal dominant disorder (only one copy of the defective gene, from either parent, is enough for disease onset)
Symptoms	Movement Disorders: Involuntary movements (chorea), muscle problems (dystonia), abnormal eye movements. Cognitive Disorders: Difficulty in organizing and focusing, lack of flexibility, impulse control issues. Psychiatric Disorders: Depression, mood swings, changes in personality
Age of Onset	Typically between 30 and 50 years of age, but can vary widely Gradual onset, worsening over 10-25 years, leading to severe disabilities
Diagnosis	Genetic testing to detect the presence of the defective gene
Treatment	No cure; treatment focuses on managing symptoms, including medication for movement and psychiatric disorders, and therapy
Impact on Life Expectancy	Can shorten life expectancy, particularly if onset is at a younger age

Genetic Mutation: Huntington’s disease is caused by a mutation in the HTT gene, leading to abnormal huntingtin (Htt) proteins that damage neurons.
Polyglutamine Tracts: The severity of the disease correlates with the length of glutamine repeats in the Htt protein; longer repeats result in earlier and more severe symptoms.
Inheritance Pattern: The disease manifests even if only one copy of the HTT gene is mutated, demonstrating its dominant nature.
Similar Proteins and Diseases: Other proteins with polyglutamine tracts, when mutated, can also cause neuronal degeneration, leading to disorders like spinocerebellar ataxia.

Genetic Engineering in Flies: Researchers engineered fruit flies to express the human HTT gene with extended polyglutamine tracts in their neurons.
Gal4/UAS System: Utilizing the Gal4 gene from baker’s yeast, the study induced expression of mutated HTT in fly neurons.
Symptoms in Flies: Flies with longer glutamine tracts exhibited symptoms similar to Huntington’s disease, unlike those with shorter, normal tracts.

Gene Expression Experiment: The study explored the effects of altering the expression of 32 genes on disease-like symptoms in fruit flies.
Yod1’s Protective Role: Overexpression of the Yod1 gene eliminated neurodegeneration and other disease-like effects in flies with longer glutamine tracts.

Broader Implications and Future Research

Potential in Human Treatment: If overexpression of the human version of Yod1 shows similar benefits in fruit flies, it could be a promising avenue for treating Huntington’s in humans.
Value of Model Organisms: Studies in fruit flies and yeasts are pivotal for understanding molecular mechanisms of diseases like Huntington’s.