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

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

Animation ed.9: 9.2&9.17 TRANSLATION

Animation ed.9: 9.2&9.17 TRANSLATION

Now, insertions and deletions of base pairs:

Forward mutation

Reverse mutation

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

Intergenic suppressor

Nonsense suppressor

Animation ed9: 9.19a Nonsense mutation

Animation ed9: 9.19b Nonsense suppressor

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

Regulatory Coding

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

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

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

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

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

CGCGCG vs. CGCGCGCGCG vs. CGCG

~1990

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

Types of mutations

+-+- Screening For Mutations

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Neurospora