1. Mutation: The Source of Genetic Variation Chapter 11

2. What is a mutation & why does it happen?  A mutation is a change in the nucleotide sequence of a DNA molecule.  Ex:  Mutation can occur spontaneously as a result of errors in DNA replication or  be induced by exposure to radiation or chemicals (called mutagens)

3. Mutations in Somatic cells versus germ cells  A mutation in a somatic cell can be passed on to descendent cells only NOT to offspring.  Mutation in skin cell – only to skin cells produced by mitosis from that particular cell  Mutations in somatic cells increase cancer risk (in that particular individual)  Only mutations in germ cells (sex cells) can be passed on to offspring.

4. 11.3 Measuring Spontaneous Mutation Rates  Studies of mutation rates in a variety of traits indicate that mutations in the human genome are rare events;  about 1 in 1 million copies of a gene is used by geneticists as the average mutation rate for humans.  Mutation rate The number of events that produce mutated alleles per locus per generation

5. Why Do Genes Have Different Mutation Rates?  Several factors influence mutation rate Size of the gene: Larger genes have higher mutation rates Nucleotide sequence: Presence of nucleotide repeats are associated with higher mutation rates Spontaneous chemical changes: C/G base pairs are more likely to mutate than A/T pairs

6. 11.4 Environmental Factors Influence Mutation Rates  Environmental agents, including radiation and chemicals, can cause mutations  Chernobyl – April 1986

7. Types of Radiation  Ionizing radiation Radiation that produces ions during interaction with other matter, including molecules in cells  Background radiation Radiation in the environment that contributes to radiation exposure

8. How Much Radiation Are We Exposed To?  Rem Unit of radiation exposure used to measure radiation damage in humans The amount of ionizing radiation that has the same effect as a standard amount of x-rays  Millirem A rem is equal to 1,000 millirems

9. US Sources of Radiation Exposure  In the US, the average person is exposed to about 360 mrem/year, 82% of which is natural Mutations in somatic cells increase cancer risk

10. Chemicals Can Cause Mutations  Some chemicals cause nucleotide substitutions or change the number of nucleotides in DNA  Other chemicals structurally change the bases in DNA, causing a base pair change after replication

11. Two Types of Mutations  Nucleotide substitutions Mutations that involve replacing one or more nucleotides in a DNA molecule with other nucleotides Ex: ACG to ATG  Frameshift mutations Mutational events in which a number of bases (other than multiples of three) are added to or removed from DNA, causing a shift in the codon reading frame Ex: ACG to ACGT (insertion); or to AG (deletion)

12. Nucleotide Substitutions  Three types of nucleotide substitutions Missense mutations Sense mutations Nonsense mutations

13. Missense Mutations  Missense mutations Mutations that cause the substitution of one amino acid for another in a protein  Example: The GAG codon (glu) in hemoglobin can mutate to  GUG (val),  AAG (lys), or  GCG (ala)

14. Sense Mutations  Sense mutations Mutations in a single nucleotide can change a termination codon into one that codes for an amino acid, producing elongated proteins  Example: Stop codon UAA in alpha globin can mutate to CAA (glu)

15. Nonsense Mutations  Nonsense mutations Mutations that change an amino acid specifying a codon to one of three termination codons producing a shortened protein  Example: A UAU codon (tyr) in beta globin can mutate to a stop codon UAA

16. Frameshift Mutations Are Caused by Nucleotide Deletions and Insertions  Insertions & deletions change the reading frame, changing the amino acids in the protein from the point of the mutation through the rest of the protein.

17. Frameshift Mutations Are Caused by Nucleotide Deletions and Insertions  THE FAT CAT ATE HIS HAT Normal code  THE FAA TCA TAT EHI SHA T Insertion  THE FTC ATA TEH ISH AT Deletion

18. Gene Expansion is Related to Anticipation  Anticipation Onset of a genetic disorder at earlier ages and with increasing severity in successive generations

19. Keep In Mind  Mutations in DNA can occur in several ways, including nucleotide substitution, deletion, and insertion

20. 11.6 Mutations and DNA Damage Can Be Repaired  Not all mutations cause genetic damage  Cells have enzyme systems that repair DNA Correct errors in replication Repair damage caused by environmental agents such as ultraviolet light, radiation, and chemicals

21. Keep In Mind  Damage to DNA can be repaired during DNA synthesis and by enzymes that repair damage to DNA caused by radiation or chemicals

22. DNA Polymerase  DNA polymerase corrects mistakes in DNA replication (proofreading function)

23. Genetic Disorders Can Affect DNA Repair Systems  Several genetic disorders, including xeroderma pigmentosum, are caused by mutations in genes that repair DNA (correlated with cancer)

24. 11.7 Mutations, Genotypes, and Phenotypes  In most genes associated with a genetic disorder, many different types of mutations can cause a mutant phenotype  In the cystic fibrosis gene, many different mutations have been identified, including deletions, nucleotide substitutions, and frameshift mutations

25. 11.8 The Type and Location of a Mutation Within a Gene Are Important  The wide range of mutations in genetic disorders leads to wide variation in clinical symptoms Depending on the mutation, symptoms can range from very mild to very severe  More than 1,500 different mutations have been discovered in the CFTR gene Some people carry two different mutations (compound or double heterozygotes)

26. 11.9 Genomic Imprinting Is a Reversible Alteration of the Genome  Genomic imprinting alters the expression of normal genes, depending on whether they are inherited maternally or paternally  Genomic imprinting When expression of a gene depends on whether it is inherited from the mother or the father Also known as genetic or parental imprinting

27. Genomic Imprinting and Genetic Disorders  Only segments of chromosomes 4, 8, 15, 17, 18, and 22 are imprinted  Disorders of chromosome 15 (80% of cases) Prader-Willi syndrome (PWS): deletion on the paternal copy Angelman syndrome (AS): deletion on the maternal copy

28. Genomic Imprinting and Genetic Disorders  Uniparental disomy (UPD) A condition in which both copies of a chromosome are inherited from one parent  About 20% of PWS and AS cases have no deletions, but UPD has been identified PWD: Both copies come from the mother AS: Both copies come from the father

29. Genomic Imprinting is Not Permanent  In each generation, the previous imprinting is erased and the gene is reimprinted During gamete formation or early development  Imprinting is an epigenetic change Involving reversible changes by chemical modifications to DNA and gene function without affecting the nucleotide sequence