LECTURE 5: HUNTING FOR MUTANTS

What is a mutant? A mutant is different than “normal”. The mutant characteristic is passed on to the next generation.

Central Dogma of Biology DNA -> RNA -> Protein DNA mRNA Transcription Translation Protein Gene Function

Mutations Often Result in the Synthesis of Abnormal Proteins DNA mRNA Transcription Translation Protein DNA -> RNA -> Protein X Abnormal Gene Function

Mutation of the Fly dpp gene

Mutation of the Fly dpp gene

Recessive versus Dominant Mutations/Alleles Allele: A particular variant of a gene (could be normal or mutant). Recessive mutations: Both copies of the gene must be mutated to manifest defect (homozygous). Loss-of-function mutations are typically recessive. Recessive mutations are represented by lower case letters. + = wildtype, m = recessive mutation Dominant mutations: The defect is manifest when only copy of the gene is mutated (heterozygous). Dominant mutations can confer new activities or interfere with normal gene function. Dominant mutations are represented by upper case letters. + = wildtype, M = dominant mutation

Genotype versus Phenotype Genotype: The genetic make-up of an individual. Examples: +/+, +/m, m/m, +/M Phenotype: The appearance of an individual. Example: Individuals having a +/+ or +/m genotype have a normal phenotype. Individuals having m/m genotype have mutant phenotype. Individuals with one normal (+) and one mutant (m) copy of a gene are called carriers for the mutation (+/m).

Abe Lincoln

One quarter of the offspring from two Marfan carrier parents will have Marfan Syndrome + mf Two types of mother’s eggs Two types of father’s sperm +/mf +/+ mf/+ mf/mf + mf or +/mf mf/+ = 1/2 offspring = Normal +/+ = 1/4 offspring = Normal mf/mf = 1/4 offspring = Marfan

Putting Mutations Into Groups A. Two Genes Function in a Common Process

Putting Mutations Into Groups B. Two non-responding mutations in the same gene Mutant m1 Mutant m*1 Signal lacking -> No response Signal lacking -> No response m1 m*1 Signal lacking -> No response

Putting Mutations Into Groups C. Two non-responding mutations in different genes Mutant m1 Mutant m2 Signal lacking -> No response Receptor lacking -> No response m1 Normal offspring + m2 Signal and Receptor present -> Response

The Body Plan of a Fly Maggot V Head Thorax Abdomen Tail “Denticle” Hairs Skin Nervous System (inside)

Fly Embryonic Patterning Mutants Anterior-Posterior Patterning Mutants Dorsal-Ventral Patterning Mutants