Single gene inheritance GENETICS it will help you
- 2. Overview and Concepts • Single-gene (Mendelian) disorders result from pathogenic variants in one gene. • Inheritance can be dominant, recessive, or X-linked. • Family pedigree analysis helps identify the likely mode of inheritance. • Affected individuals typically show patterns over generations, making these disorders traceable.
- 3. Genotype and Phenotype • Genotype: The genetic makeup (e.g., mutation in a gene like CFTR). • Phenotype: The observable traits or clinical symptoms. • Two people with the same genotype may show different phenotypes due to modifier genes or environment. • Homozygous = two identical alleles; Heterozygous = two different alleles.
- 4. Autosomal Dominant Inheritance • One mutated allele is sufficient to cause disease. • Vertical transmission: appears in multiple generations. • Affected individuals have a 50% chance of passing the mutation to offspring. • Examples: Marfan syndrome, Achondroplasia, Neurofibromatosis type 1 (NF1). Often due to: • Haploinsufficiency • Dominant-negative effect • Gain-of-function mutations
- 5. Autosomal Recessive Inheritance • Two mutated alleles are needed (homozygosity or compound heterozygosity). • Parents of affected children are typically asymptomatic carriers. • Horizontal pattern: disease often seen in siblings, not parents. • 25% risk of disease in offspring of two carrier parents. • Examples: Cystic fibrosis, Phenylketonuria (PKU), Tay-Sachs disease.
- 6. Sex-limited Phenotype in Autosomal Dominant Diseases • Gene is autosomal, but phenotype is expressed only in one sex. • Common in traits tied to sexual physiology (e.g., male-limited precocious puberty). • Genotype may be present in both sexes, but only one sex shows the disease.
- 7. Penetrance • Penetrance = proportion of individuals with a mutation who express the phenotype. • Complete penetrance = everyone with the mutation shows symptoms. • Incomplete (reduced) penetrance = some mutation carriers remain unaffected. Influenced by: • Age • Environment • Modifier genes Example: BRCA1 mutations show incomplete, age-dependent penetrance for breast/ovarian cancer.
- 8. Expressivity • Expressivity = variation in disease severity or symptoms among individuals with the same genotype. May be: • Variable expressivity – same mutation, different clinical features. • Seen in Neurofibromatosis type 1: mild café-au-lait spots vs. severe tumors. • Expressivity is influenced by: • Modifier genes • Environmental triggers • Epigenetic factors