16 and 18 March, 2004 Chapter 14 From Gene to Phenotype Dominance, epistasis, gene interaction

Overview Genetic and environmental contributions interact to determine phenotype. Mutations in same gene usually result in mutant phenotype when present together. Mutations in different genes complement. Dominance comes in several types. Most characters are determined by sets of genes that interact with the environment. Modified genetic ratios reveal gene interactions, including epistasis.

Complementation test Diagnostic test for allelism Mutants are crossed to bring two recessive mutations together in heterozygous form –if phenotype is mutant, mutations are in same gene they fail to complement both have loss of function –if phenotype is wild-type, mutations are in different gene each mutant contributes normal gene at different locus complementation due to interaction of different proteins Heterokaryons used in haploid organisms

Interactions between alleles Dominant versus recessive Incomplete dominance –intermediate phenotype –1:2:1 F 2 ratio –quantitative differences in gene dose Codominance –equal presence of two gene products –ABO blood groups –sickle-cell hemoglobin Hb A dominant for lack of anemia Hb A and Hb B codominant for hemoglobin Alleles of a single gene can show various degrees of dominance. Dominance is determined by type of molecular interaction and level of analysis.

Lethal alleles Cause death of organisms Recessive lethals masked in heterozygotes by wild-type allele Example: yellow coat color in mice –A Y is dominant for color –A Y is recessive lethal A Y /A  A Y /A 25% A Y /A Y lethal 50% A Y /Ayellow 25% A/A wild-type Example of pleiotropism: gene affects multiple characters

Lethal mutation Change in DNA sequence resulting in change in amino acid sequence Genetic load: total of deleterious and lethal genes in population Often result of lack of activity or abnormal activity of encoded protein Lethality affected by genetic and physical environment Detected by abnormal genetic ratios

Epistasis Allele of one gene eliminates expression of alleles of another gene, substituting its own phenotype Usually indicative of biochemical or developmental pathway (sequential gene activity) Involves genes at two or more loci Results in dihybrid F 2 ratios that deviate from 9:3:3:1

B- Black bb Brown E- Deposition ee No deposition in hairs

Two pathways - black, orange

Suppression Interaction between two molecules Product of one allele of a gene interferes with product of another gene on a different pathway Numerous causes –nonsense suppressors mutant tRNA that reads premature stop codon –protein-protein interactions

Coat color in mammals Five major genes, A, B, C, D, and S A: affects distribution of pigment in hair –A: agouti, yellow band on dark shaft –a: nonagouti, no yellow; solid pigment B: determines color of melanin –B = blackb = brown C: permits color; c: no color D: full intensity; d: dilute color (uneven) S: no spots; s: spots (piebald)

Penetrance and expressivity Penetrance –percent individuals with a given allele that show the phenotype of the allele –<100% penetrance a result of modifiers, epistasis, suppressors, environmental conditions Expressivity –extent to which allele is expressed at phenotypic level –affected by genetic background and environment These phenomena make pedigree analysis and genetic counseling more difficult

Assignment: Concept map, Solved Problems1 and 2, All Basic and Challenging Problems. Problems are particularly important for this chapter.