1. Mutation and Disease

2. Why Study Our DNA? Learn the effects of mutations Understand how genetic diseases are generated Propose possible treatments for genetic diseases Identify causes of genetic diseases Unfortunately, inheritance is mostly NON-Mendelian – The alleles for traits are passed on and expressed in complex ways

3. Mutations Mutation  Any change in the DNA sequenceMutation  Any change in the DNA sequence Mutations can be good, neutral, or badMutations can be good, neutral, or bad Most mutations are badMost mutations are bad Types:Types: 1)Point mutation 2)Frame shift 3)Chromosomal Mutations can be caused by:Mutations can be caused by: mistakes in replication of DNAmistakes in replication of DNA mistakes in cellular divisionmistakes in cellular division external forcesexternal forces

4. Agents of Mutation Mutagen  Any substance that can cause a change inMutagen  Any substance that can cause a change in 1) Radiation: X rays, cosmic rays, ultraviolet light, and nuclear radiation 2) Chemicals: dioxins, asbestos, benzene, and formaldehyde Carcinogens  chemicals that cause cancer, often by mutating the DNA Carcinogens  chemicals that cause cancer, often by mutating the DNA 3) High temperatures and Pressure

5. Point mutation  is a change in a single base pair in DNA. Point mutation  is a change in a single base pair in DNA. A point mutation in the base pairs of a codon can change an amino acid A point mutation in the base pairs of a codon can change an amino acid Codon  3 bases in DNA chain Codon  3 bases in DNA chain 1 codon = 1 amino acid 1 codon = 1 amino acid Not all point mutations cause a change Not all point mutations cause a change Mutation may code for same amino acid Mutation may code for same amino acid CCC, CCA, and CCG all code for Proline CCC, CCA, and CCG all code for Proline Point Mutations

6. Point Mutation of Sickle Cell Anemia Glutamate changed to Valine Shape of hemoglobin changes Hemoglobin causes: Sickle shape Sickle shape Low O 2 levels in cell Low O 2 levels in cell Painful and slow blood movement in capillaries Painful and slow blood movement in capillaries

7. Frame Shift Mutations Frame shift  A mutation in which a 1 or more bases are added to or deleted from DNA Frame shift  A mutation in which a 1 or more bases are added to or deleted from DNA Very dangerous mutation. Why? Very dangerous mutation. Why? – Could change every amino acid on from the site of the mutation – Completely different protein that may not function AT ALL

8. Chromosomal Mutations Major change in a chromosome's structure or the number of chromosomes in a gamete 4 Types: 1)Deletion 2)Duplication 3)Translocation 4)Inversion

9. Deletions and Duplications Deletion  section of chromosome is lost – Cri-du-chat (cat’s cry) – Deletion from Chromosome 5 causes mental retardation and bad formed larynx – Cry sounds like cat meow Duplication  Copy of DNA section is inserted to a chromosomes that already has that section – Why can two copies be good? – Test out mutation – One mutated copy tests new protein while normal protein does normal functions – Hemoglobin in humans has evolved this way

10. Translocation and Inversion Translocation  section of DNA is switched with non- homologous chromosome – Typically reciprocal (two chromosomes each have translocation) – Philadelphia Chromosome  translocation of #9 and #12; causes uncontrolled growth in white blood cells (leukemia) Inversion  DNA switches order in chromosome – Genes lose function or produce harmful/helpful new versions

11. Non-Disjunction Non-disjunction  chromosomes fail to break apart during meiosis – Produces gametes with extra chromosomes or missing chromosomes – Polyploidy  too much DNA Most miscarriages (baby deaths before birth) are caused by this Trisomy 21 and 18  – 3 copies of #21 or #18 chromosome – Live, but lives are short and difficult X and Y polyploidy survive… – XYY? – Extra Y’s just mean more male characteristics; no essential genes – XXY and XXX? – Barr bodies turn off extra Xs

12. Human Inheritance Patterns Autosomal Recessive  – RR  no trait – Rr  carriers – rr  show the trait CF  Cystic Fibrosis – 1:4,000 births in US – Build up of thick mucus blocks lungs and promotes disease PKU  Phenylketonuria – 1:15,000 births in US – Enzyme cannot breakdown certain amino acids – Build up causes brain damage – Must be medicated and restrict diet

13. Human Inheritance Patterns Autosomal Dominate  – RR  have trait – Rr  have trait – rr  no trait Dwarfism  Achondroplasia – 1:25,000 births worldwide – Only heterozygous survive to be born – Defective cartilage leads to short arms and legs; large heads; regular sized body

14. Human Inheritance Patterns X-Linked Recessive  – XX  no trait – XX r  carries – X r X r  have trait DMD  Duchenne muscular dystrophy – Muscle tissue degrades; most cannot walk or need crutches X-Linked Dominate  – XX  have trait – X r X r  no trait – Extremely rare in humans. Why? Effects both men and women equally Less likely to reproduce