1. a+ --> a- mutation (forward mutation) a- --> a+ reverse mutation (reversion)

2. Amorph Hypomorph Hypermorph Neomorph Presence of pink pigment + / - An ALLELIC SERIES for this gene

6. Animation ed.9: 9.2&9.17 TRANSLATION

8. Animation ed.9: 9.2&9.17 TRANSLATION

16. Now, insertions and deletions of base pairs:

18. Forward mutation

19. Reverse mutation

21. Equivalent reversion UCC (Ser) forward UGC (Cys) reverse AGC (Ser) Wild typeMutantWild type CGC (Arg, basic) forward CCC (Proline) reverse CAC (His, basic) Wild typeMutant Pseudo-wild type Intragenic suppressor

23. Intergenic suppressor

24. Nonsense suppressor

26. Animation ed9: 9.19a Nonsense mutation

27. Animation ed9: 9.19b Nonsense suppressor

28. Animation 9.19c Nonsense suppression rod ns and suppressor-tRNA together give WT phenotype

33. Regulatory Coding

37. Series of slides on molecular markers / genetic mapping (RF)

38. When doing GENETIC mapping, Molecular Markers can be used as a locus Single Nucleotide Polymorphisms (SNPs) AACGTCATCG vs. AACGTTATCG Microsatellites (variable # of short repeats) CGCGCG vs. CGCGCGCGCG vs. CGCG Restriction Fragment Length Polymorphism (RFLP) SNP leading to a loss/gain of a restriction cut site

39. When doing GENETIC mapping, Molecular Markers can be used as a locus They are mile-markers, not destinations! אבני דרך, ולא יעדים! Almost all SNPs, Microsatellites, etc. are SILENT, and there are millions of them

40. Is there linkage between a mutant gene/phenotype and a SNP? USE standard genetic mapping technique, with SNP alternative sequences as “phenotype” B= bad hair, Dominant X B/b b/b B/b b/b 1/1’ 25% 1/1 25% 1/1’ 25% 1/1 25% 1/1’ 1/1 SNP1..ACGTC.. SNP1’..ACGCC.. SNP2..GCTAA.. SNP2’..GCAAA.. SNP3..GTAAC.. SNP3’..GTCAC.. 2/2’ 47% 2/2 3% 2/2’ 3% 2/2 47% 2/2’ 2/2 3/3’ 25% 3/3 25% 3/3’ 25% 3/3 25% 3/3’ 3/3 SO…B is 6 cM from SNP2, and is unlinked to SNP 1 or 3 B 2’ / b 2

41. Is there linkage between a mutant gene/phenotype and a SNP? USE standard genetic mapping technique, with SNP alternative sequences as “phenotype” B= bad hair, Dominant X B/b b/b 1/1’ 1/1 SNP1..ACGTC.. SNP1’..ACGCC.. SNP2..GCTAA.. SNP2’..GCAAA.. SNP3..GTAAC.. SNP3’..GTCAC.. 2/2’ 2/2 3/3’ 3/3 SO…B is 6 cM from SNP2, and is unlinked to SNP 1 or 3 We have the ENTIRE genome sequence of mouse, so we know where the SNPs are Now-do this while checking the sequence of THOUSANDS of SNPs

43. CGCGCG vs. CGCGCGCGCG vs. CGCG

45. ~1990

48. Screening for mutations Finding the very rare cases where NEW ALLELES arise

49. Types of mutations

53. +-+- Screening For Mutations

54. ad - ad + Screening For Reversions

64. Neurospora