MUTATIONS Changes in DNA that affect genetic information

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

What Causes Mutations? There are two ways in which DNA can become mutated:  Mutations can be inherited. Parent to child  Mutations can be acquired. Environmental damage Mistakes when DNA is copied

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) Immunity to HIV

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

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.

DNA (antisense strand) mRNA Polypeptide Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids The antisense strand is the DNA strand which acts as the template for mRNA transcription

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

Point Mutation Sickle Cell disease is the result of one nucleotide substitution Occurs in the hemoglobin gene

Mutations: Substitutions Substitution mutation GGTCACCTCACGCCA ↓ CCAGUGGAGUGCGGU ↓ 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 © 2010 Paul Billiet ODWSODWS

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

Disaster Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Substitution mutation GGTCTCCTCACTCCA ↓ CCAGAAGAGUGAGGU ↓ Pro-Glu-Glu-STOP © 2010 Paul Billiet ODWSODWS

Frameshift Mutation Original:  The fat cat ate the wee rat. Frame Shift (“a” added):  The fat caa tat eth ewe era t.

Mutations: Additions Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Addition mutation GGTGCTCCTCACGCCA ↓ CCACGAGGAGUGCGGU ↓ Pro-Arg-Gly-Val-Arg A frame shift mutation © 2010 Paul Billiet ODWSODWS

Mutations: Deletions Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Deletion mutation GGTC/CCTCACGCCA ↓ CCAGGGAGUGCGGU ↓ Pro-Gly-Ser-Ala-Val A frame shift mutation © 2010 Paul Billiet ODWSODWS

Gene Mutation Animation

Phenylketonuria Background to Phenylketonuria Phenylalanine and tyrosine are two amino acids that humans obtain from protein in their diet. During normal metabolism, excess phenylalanine is acted upon by an enzyme (phenylalanine hydroxide). 20

Phenylketonuria: aka - PKU PKU is a hereditary disorder caused by a genetic defect which disrupts this metabolic pathway. An affected person lacks the normal allele of the gene required to make the enzyme Phenylalanine Hydroxide 21

Phenylketonuria: Continued Owing to this inborn error in metabolism, phenylalanine is no longer converted to tyrosine. Instead it undergoes alternative pathways which produces toxins which affect the metabolism of brain cells and severely limit mental development. 22

Screening for PKU – Newborn babies are screened for PKU, and sufferers are put on a diet containing minimum phenylalanine. As a result the worst effects of PKU can be kept to a minimum. 23

Albinism Albinism results from a mutation which prevents the formation of enzyme 3 (Melanocyte Tyrosinase). As a result albinos fail to synthesize melanin. 24

Albinism – the symptoms Due to the total lack of the pigment melanin Albino’s have characteristic  Very pale skin which fails to tan.  White hair  The colour of the iris is usually blue/gray or light brown with some people having a reddish or violet hue reflected through the iris.  In some cases there is vision problems. They must avoid ultraviolet radiation and may require to ware tinted glasses to assist with photophobia. 25

Albinism 26

Cystic Fibrosis Mucus is a slimy substance secreted by the inner lining of the wind pipe and intestine. Mucus is made of a glycoprotein which makes it thick, slimy and perfect for protection and lubrication. The genetic information for coding this glycoprotein is on chromosome 7. 27

Cystic fibrosis: due to gene mutation If the info on the gene for the glycoprotein is altered.... Two outcomes Homozygous for the mutant allele: Make abnormally thick and sticky mucous leading to lung congestion and blockage of the pancreatic duct = CYSTIC FIBROSIS. 2. Heterozygous for the mutant allele: they carry the mutant allele masked in their genotype 28

Cystic fibrosis 10/08/201529

Mutagenic agents – Increases mutation rate. These include  A variety of chemicals act as mutagens. E.g. Bromouracil, are structurally similar to DNA bases, and are inserted in place of normal bases. Ethidium bromide has a structure that allows it to wedge within the DNA double helix Peroxides and mustard gas, chemically modify DNA.  Exposure to high-energy radiation (bombardment by alpha, beta, or gamma particles) or ultraviolet light can have a similar effect. 30

Example of chemical mutations Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities31

The Chernobyl Babies – Radiation causes birth defects 32

Some mutations even make it on SNL!