MUTATIONS

WHAT ARE MUTATIONS? Changes in the nucleotide sequence of DNA May occur in somatic cells (aren’t passed to offspring) May occur in gametes (eggs & sperm) and be passed to offspring

ARE MUTATIONS HELPFUL OR HARMFUL? Mutations happen regularly Almost all mutations are neutral Chemicals & UV radiation cause mutations Many mutations are repaired by enzymes

ARE MUTATIONS HELPFUL OR HARMFUL? Some type of skin cancers and leukemia result from somatic mutations Some mutations may improve an organism’s survival (beneficial) Mutagen any thing That causes mutations

CAUSES OF MUTATIONS Any thing that causes mutations is called mutagen A mutagen that causes mutations resulting in cancer is carcinogen A high frequency UV light contains enough energy to cause a point mutation. One in nine canadians will develop cancer at some point in life. X-rays also cause mutaions by breaking the backbone of DNA spontaneous mutations occurring without chemical change or radiation but as a result of errors made in DNA replication Induced mutations may also be caused by exposure to chemicals. Numerous pesticides have been linked to deleterious mutations and have now been banned in Canada and other parts of the world.

INDUCED MUTATIONS Caused by mutagens rather than spontaneous Induced mutations may also be caused by exposure to chemicals. Numerous pesticides have been linked to deleterious mutations and have now been banned in Canada and other parts of the world. Cystic fibrosis is another example of a genetic disease. It is caused by any one of at least 60 different types of mutations in the CFTR gene. The severity of cystic fibrosis varies with the location of the mutation. Missense, splicing, nonsense, and frameshift mutations have been characterized in the CFTR gene, all causing cystic fibrosis. The most common mutation is a 3-base-pair deletion discovered in Toronto at the Hospital for Sick Children by Dr. Lap-Chee Tsui and his research team.

Chemicals that resemble DNA can also cause mutations. This capability has been taken advantage of in AIDS therapy. Some of the chemicals in AIDS drugs resemble the nitrogenous bases in DNA and insert themselves into the virus’s DNA.When the viral DNA is to be duplicated, the DNA polymerase stops because it does not recognize the substituted chemical as a base. The progression of the disease is slowed.

TYPES OF MUTATIONS

CHROMOSOME MUTATIONS May Involve: Changing the structure of a chromosome The loss or gain of part of a chromosome

CHROMOSOME MUTATIONS Five types exist: Deletion Inversion Translocation Nondisjunction Duplication

DELETION Due to breakage A piece of a chromosome is lost

INVERSION Chromosome segment breaks off Segment flips around backwards Segment reattaches

DUPLICATION Occurs when a gene sequence is repeated

TRANSLOCATION Involves two chromosomes that aren’t homologous Part of one chromosome is transferred to another chromosomes

TRANSLOCATION

NONDISJUNCTION Failure of chromosomes to separate during meiosis Causes gamete to have too many or too few chromosomes Disorders: Down Syndrome – three 21 st chromosomes Turner Syndrome – single X chromosome Klinefelter’s Syndrome – XXY chromosomes

CHROMOSOME MUTATION ANIMATION

GENE MUTATIONS Change in the nucleotide sequence of a gene May only involve a single nucleotide May be due to copying errors, chemicals, viruses, etc.

TYPES OF GENE MUTATIONS Include: Point Mutations Substitutions Insertions Deletions Frameshift

POINT MUTATION Change of a single nucleotide Includes the deletion, insertion, or substitution of ONE nucleotide in a gene

No change Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Substitution mutation GGTCTTCTCACGCCA ↓ CCAGAAGAGUGCGGU ↓ Pro-Glu-Glu-Cys-Gly

Mutations: Substitutions Substitution mutation GGTC A CCTCACGCCA ↓ CCAG U GGAGUGCGGU ↓ Pro- Arg -Glu-Cys-Gly Substitutions will only affect a single codon Their effects may not be serious unless they affect an amino acid that is essential for the structure and function of the finished protein molecule (e.g. sickle cell anaemia) Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids

Mutations: Inversion Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Inversion mutation GGTCCTCTCACGCCA ↓ CCAGGAGAGUGCGGU ↓ Pro-Gly-Glu-Cys-Gly Inversion mutations, also, only affect a small part of the gene

MISSENSE MUTATIONS missense mutation a mutation that results in the single substitution of one amino acid in the resulting polypeptide

POINT MUTATION Sickle Cell disease is the result of one nucleotide substitution Occurs in the hemoglobin gene

FRAMESHIFT MUTATION Inserting or deleting one or more nucleotides Changes the “ reading frame ” like changing a sentence Proteins built incorrectly

FRAMESHIFT MUTATION Original: The fat cat ate the wee rat. Frame Shift (“a” added): The fat caa tet hew eer at.

AMINO ACID SEQUENCE CHANGED

GENE MUTATION ANIMATION

NORMAL MALE 32 2n = 46

NORMAL FEMALE 33 2n = 46

MALE, TRISOMY 21 (DOWN’S) 34 2n = 47

FEMALE DOWN’S SYNDROME 35 2n = 47

KLINEFELTER’S SYNDROME 36 2n = 47

TURNER’S SYNDROME 37 2n = 45