Genetics Basic Genetics Humans - 23000 genes, 37 mitochondrial genes, 13 encode protein Drosophila melanogaster - 17000 genes, 4 chromosomes: X/Y, 2, 3, 4 Never recombination on chromosome 4 or in males Males are smaller, solid pigmentation on dorsal abdomen, rounded, sex combs Possible mutagen phenotypes - smaller wings, white eyes, smaller bodies, shorter bristles Sex determined in flies by ratio of X chromosomes to autosomes Morgan - found chromosomes responsible for genetic inheritance Hemizygous - only one copy of a gene Recombination frequency = (# recombinant progeny / total # progeny) x 100 (cM or map units) Multigenic traits - continuous, eg hair colour Polycistronic - several genes per mRNA Genetic Defects Holoprosencephaly - eyes closer together, single central incisor Haplo-insufficient - gene present in only one functional copy - the lack of DNA becomes dominant Autosomal dominant - Huntington's Autosomal recessive - Cystic fibrosis X-linked recessive - red-green colorblindness, haemophilia X-linked dominant - vitamin D-resistant rickets, males pass on to all daughters Incomplete dominance - heterozygote has intermediate phenotype, eg pink flowers Co-dominance - heterozygote is sum of two phenotypes, eg lentil seed pattern - spotted and dotted Over-dominance - heterozygote advantage, eg sickle cell disease in relation to malaria resistance Under-dominance - heterozygote disadvantage Blood type O allele has single base pair deletion - frameshift A allele - alpha-N-acetylgalactosamine B allele - alpha-N-galactose A and B are codominant O is recessive to A and B Pleiotropy - a single mutation can affect multiple processes, eg protein phosphatase 1 Sickle cell disease - homozygous for Hbßs, recessive at disease level 1
Mutant allele dominant in malaria resistance Hbßa and Hbßs codominant in respect to protein production Incomplete dominance shown with RBC count at high altitude Epistasis - flower colour, blood group Locus for blood antigen basic structure at H H-/H- individuals are blood group O irrespective of alleles at locus I Functional H+ alleles -> IA, IB, IO alleles expressed Penetrance - % of population displaying expected phenotype Reduced penetrance - juvenile glaucoma, BRCA1 Phenylketonuria - genetic defect appears environmental - loss of function allele for phenylalanine hydroxylase gene - build up causes defect in brain development Treat with low protein diet -> introduce new protein foodstuff and disease appears environmental Mutations Missense mutation - substitutes one amino acid for another, eg sickle cell anaemia: glutamate -> valine Nonsense mutation - premature stop codon, eg muscular dystrophy Frameshift mutation - insertion/deletion of DNA not divisible by three - alters reading frame Loop of DNA forms at the site of a deletion Conditional mutant - can be switched on/off eg by temperature Mutagen - increases rate of mutation Transition mutation - purine-purine / pyrimidine-pyrimidine Transversion mutation - purine-pyrimidine Auxotroph - requires additional substance in media to grow, opposite of prototroph Revertant - base-pair change from wild type to auxotroph reverses back to original pair Pseudorevertant - base-pair changed to suppress original mutation but not to original pair Chaperones - hide mutations by squashing the protein back into shape Mitochondrial