Q8.Which of the following disease in humans is caused due to expanded microsatellite repeats?
(A) Huntington’s disease
(B) Cystic fibrosis
(C) Tuberculosis
(D) Alcaptonurea
Huntington’s disease (A) is caused by expanded microsatellite repeats, specifically CAG trinucleotide repeats in the HTT gene.
This leads to a toxic polyglutamine tract in the huntingtin protein, causing progressive neurodegeneration.
Option Breakdown
Huntington’s disease (A): Autosomal dominant disorder from >36 CAG repeats (normal: <36) in exon 1 of HTT on chromosome 4. Expansion causes protein misfolding, neuronal death in basal ganglia, chorea, cognitive decline, and psychiatric symptoms. Classic microsatellite expansion disease.
Cystic fibrosis (B): Autosomal recessive, caused by CFTR gene mutations (most common: ΔF508 deletion). Chloride channel dysfunction leads to thick mucus in lungs, pancreas. Not repeat expansion; point mutations/deletions dominate.
Tuberculosis (C): Infectious disease from Mycobacterium tuberculosis. No genetic basis via microsatellite repeats; environmental exposure and immune response determine susceptibility.
Alkaptonuria (D): Autosomal recessive, HGD gene mutations cause homogentisate accumulation, darkening connective tissues (ochronosis), arthritis. Single nucleotide variants, not repeat expansions.
Introduction to Microsatellite Repeat Diseases
Expanded microsatellite repeats Huntington’s disease represents a key example of trinucleotide repeat disorders where CAG expansions in the HTT gene exceed 36 repeats, producing neurotoxic polyglutamine proteins. These dynamic mutations show anticipation, worsening across generations. Critical for genetics, neurology exams, and research in molecular biology and neurodegeneration.
Mechanism of Repeat Expansion Pathology
Microsatellites (1-6 bp repeats) become pathogenic when expanded beyond thresholds.
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Gain-of-function toxicity: CAG repeats translate to polyQ tracts causing protein aggregation, disrupting transcription, autophagy in neurons.
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Anticipation: Paternal transmission often shows greater expansion due to spermatogenesis replication errors.
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Threshold effect: 36-40 repeats: incomplete penetrance; >40: full disease.
