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

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

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

Mutation of the Fly dpp gene

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

Genotype versus Phenotype Genotype: The genetic make-up of an individual. Phenotype: The appearance of an individual. Examples: +/+, +/m, m/m, +/M 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

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

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 Signal lacking -> No response Mutant m1Mutant m*1 Signal lacking -> No response m*1m*1 m1

Putting Mutations Into Groups C. Two non-responding mutations in different genes Signal and Receptor present -> Response Mutant m1Mutant m2 m2m2 m1 + Normal offspring Signal lacking -> No responseReceptor lacking -> No response

Comprehensive Screening for Mutants 1) 10 mutations distributed randomly among 10 genes 2) 50 mutations distributed randomly among 10 genes

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

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