Mendelian Inheritance Patterns in Humans | University of California, San Diego

University:
University of California, San Diego
Course:
BIMM 100 | Molecular Biology
Academic year:

2024
Views:

184

Pages:

1
Author:

customer-8930767

molecular basis of Mendelian inheritance patterns in humans using one autosomal dominant, one autosomal recessive, and one X-linked disorder. Mendelian disorders arise from mutations in single genes, following predictable inheritance patterns based on chromosome location and allelic effects. Autosomal dominant – Huntington’s disease: CAG trinucleotide repeat expansion (>36 repeats) in HTT gene (chromosome 4p16.3), encoding huntingtin protein. Mutant huntingtin forms aggregates, causing neurodegeneration. Dominance mechanism: toxic gain-of-function (polyglutamine tract alters protein conformation, sequesters transcription factors). Inheritance: affected parent has 50% chance of passing to offspring; both sexes equally affected; no carrier state; penetrance is age-dependent (symptoms onset ~40 years). Anticipation occurs (earlier onset in successive generations) due to repeat instability during spermatogenesis. Autosomal recessive – Cystic fibrosis (CF): Mutations in CFTR gene (7q31.2), encoding CFTR chloride channel. Common mutation ?F508 (deletion of Phe508) causes misfolding ? ER retention and degradation. Recessive mechanism: loss-of-function; heterozygotes (carriers) have 50% normal CFTR, sufficient for function. Inheritance: affected child has 25% risk if both parents carriers; consanguinity increases risk. Clinical: thick mucus in lungs/pancreas due to defective Cl? and HCO?? transport. Diagnosis: sweat chloride test (>60 mM); newborn screening by immunoreactive trypsinogen + CFTR mutation panel. X-linked recessive – Hemophilia A: Mutations in F8 gene (Xq28), encoding coagulation factor VIII. Over 2,000 mutations (inversions, deletions, point mutations) cause deficiency. Mechanism: males (XY) have one X, so a single mutant allele causes disease; females (XX) require two mutations for disease, thus are typically carriers. Inheritance: affected male cannot pass to sons (sons get Y) but passes to all daughters (carriers); carrier females have 50% chance of affected sons. Variable expressivity in carriers due to X-inactivation skewing. Treatment: recombinant factor VIII replacement; gene therapy (AAV5-hFVIII) approved.