Title HG CL 5 BASIC OF INHERITANCE.pdf ✅

HG CL 5 : BASIC OF INHERITANCE ● Distinguish between gene and allele, genotype and phenotype, wild type genes and mutant genes ● Explain mendelian inheritance and non-mendelian inheritance ● Distinguish between autosomal dominant inheritance, autosomal recessive inheritance and sex-linked inheritance ● Explain the concepts of dominance, recessive, codominance, pseudodominance, variable expressivity, reduced penetrance using examples where appropriate ● Establish the mode of inheritance of certain traits or disorder A. TERMINOLOGY : Gene Part of DNA mole of chr that direct synth of specific polypeptide chain Modifier gene Gene that laters expressions of gene @ another locus. Genome Complete set of org’s DNA inc all genes. Allele Alternative form of gene found @ same locus on homologous chr Genotype Genetic constitution of an idv Phenotype Appearance (biochem, physical, physiological) of indv that results from interaction of envi & genotype. B. FAMILY HISTORY / TREE In order to create a FH, need ; - At least; 3 generations - Use standardized symbols & terminology Consultant Indv requesting counseling Proband 1st affected member coming to medical attention Details needed in FH General Specific - Both sides of family - Full name - DOB - Date, cause of death - Any specific medical diagnoses. - Consanguinity AR inheritance - Infant deaths, still births, abortions. C. INHERITANCE PATTERN Mendelian (single gene disorder) Non-mendelian - Autosomal: dominant, recessive - X linked: dominant, recessive - Y linked - Mitochondrial - Digenic inheritance - Genomic Imprinting - Uniparental disomy - Polygenic inheritance - Pleiotropy - Cryptic chromosomal translocation


II. AUTOSOMAL RECESSIVE - Manifest when mutant allele is present in double dose – homozygous state. - Heterozygous individuals generally show no features of the disorder and are healthy – carrier Typical features : - > 1 affected children with unaffected parents - Usually only one generation involved (a single sibship of brothers & sisters: “horizontal”) - Usually in large/inbred sized families - Males and females affected with equal frequency and severity - Risk of having another affected offspring – 25% or 1⁄4 - Unaffected siblings of an affected child – 2⁄3 chance of carrier. Disease related to AR : - Thalassaemia - Inborn error of metabolism - Galactosaemia - Mucopolysaccharidoses (except Type II) Additional features : 1. Consanguinity - “Common gene pool” shared by blood relatives 1st deg Parent : child – 50% 2nd deg Aunt : nephew – 25% 3rd deg 1st cousins : 12.5% - Consanguinity ↑↑ the chance that a mating couple will both carry the same disease-causing mutation. - It is seen more often in pedigrees involving rare recessive diseases >> common recessive disease 2. Locus heterogeneity - Caused by mutations at different loci in different families, - Homozygous for mutant alleles at different loci – double heterozygotes - If 2 deaf persons marry, one would expect all their children to be affected; contrary to that, has been reported that all children have normal hearing parents were homozygous at different loci - Eg of disease : Adult polycystic kidney disease, familial Alzheimer, breast cancer, osteogenesis imperfecta.