Small-scale changes in the genome

DNA synthesis errors and their correction Does change in DNA sequence = change in protein sequence? Gene mutations and DNA repair The nature and causes of mutations DNA repair mechanisms

DNA Mutation

I. II.

Types of DNA Sequence Changes Mechanism of Mutation

Somatic vs Germ-line Mutations

General Mutation Types

Strand Slippage: Producing Insertions and Deletions

Base Substitutions: Transitions and Transversions

Wobble
Pairing rules are relaxed at the third position of the codon

Base Substitutions

Types of Mutations

Intragenic Suppressor

General Rule: If 1st mutation is a deletion, suppressor is an insertion If 1st mutation is an insertion, suppressor is a deletion
(Pierce pg 480 for example)

The Mechanisms of Mutation

D A A D D A

Cytosine

Guanosine

Spontaneous Mutations

Non-Standard Wobble Base Pairing

Chemical Mutagens: Changing Donors and Acceptors

Tri-nucleotide Repeat Disorders

8 Repeats

Mechanism of Short Repeat Expansion: 2. Slippage

13 Repeats

Mechanism of Short Repeat Expansion: 1. Unequal Crossing Over

Tri-nucleotide Repeat Disorders: Huntingtons Disease

Normal Repeat Range: 9-37

Disease Range 37-121 . This repeat occurs within the coding region of the gene These Diseases Show Anticipation

Tri-nucleotide Repeat Disorders: Huntingtons Disease

Correlation of Age of Onset with Triplet Repeat Length
100

80 60

Onset
40 20

30

40

50

60

70

80

90

100

CAG Repeats
Physician's Guide to the Management of Huntington's Disease 2nd ed.

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The Ames Test

Ames test: his+ revertants

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Genome Size: Common Building Blocks, Differing Sizes

Mutation Rates

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DNA Repair Pathways

Genetic Disease and DNA Repair

13

CFTR Mutations: Different Mutations are Different Alleles

See Pierce, pg 506-7 for PKU example

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CFTR: From Gene to Protein

Classes of Mutations: I: No Protein Translated II: Defective Protein (Degraded) III: Channel Not Regulated Correctly IV: Channel Works Poorly V: Reduced Synthesis of the Protein

CFTR Mutations: Different Alleles can have Different Effects

CFTR+/ CFTR+ CFTR-/ CFTR-

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