LECTURE 5: HUNTING FOR MUTANTS

1. LECTURE 5: HUNTING FOR MUTANTS

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

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

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

5. Mutation of the Fly dpp gene

6. Mutation of the Fly dpp gene

7. 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). Dominant mutations: The defect is manifest when only copy of the gene is mutated (heterozygous). Recessive versus Dominant Mutations/Alleles • 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

8. 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 +/mgenotype have a normal phenotype. Individuals having m/mgenotype have mutant phenotype. Individuals with one normal (+) and one mutant (m) copy of a gene are called carriers for the mutation (+/m).

9. Abe Lincoln

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

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

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

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

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

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