Human Genetic Mutations

1. Human Genetic Mutations

2. 2 Main Types of Mutations 1.) Chromosomal Mutations 2.) Gene Mutations

3. What are chromosomes? • Humans have 23 pairs of chromosomes, with one chromosome from each parent. • The chromosomes are coiled up DNA. • Under normal conditions all of the chromosomes are inherited in tact. This is a normal karyotype of human chromosomes. A karyotype is a picture of chromosomes lined up to look at and compare.

4. Chromosomal Mutations • Any change in the structure or number of chromosomes • Large scale: Affect many genes

5. 5 Types • Deletion • Duplication • Inversion • Translocation • NonDisjunction

6. Chromosomal Deletion One or more genes are removed Causes: Wolf-Hirschhorn syndrome (severe mental retardation) cri du chat syndrome (mewing sounds, mental retardation)

7. Chromosomal Duplication A segment of genes is copied twice and added to the chromosome Causes: Charcot–Marie–Tooth disease (high arched foot, claw feet, confined to a wheelchair)

8. Chromosomal Inversion a segment of genes flip end-to-end on the chromosome Causes: Four-Ring Syndrome (cleft pallate, club feet, testes don’t descend)

9. Chromosomal Translocation Material is swapped with another chromosome Causes: Burkitt’s Lymphoma (cancer of the lymph nodes, in children)

10. Nondisjunction • Chromosomes FAIL TO SEPARATE during meiosis • Meiosis I Nondisjunction • Meiosis II Nondisjunction

11. Nondisjunction • Produces gametes (and therefore a baby) with one missing chromosome or one extra chromosome

12. Nondisjunction (in Meiosis II)

13. Fertilization

14. Nondisjunction • Every cell in that baby’s body will have __ copies of this chromosome instead of___. • This condition is called ____________. • Trisomy 21 = Individual has _____ copies of chromosome # ________

15. Nondisjunction • Every cell in that baby’s body will have 3 copies of this chromosome instead of 2. • This condition is called __________. • Trisomy 21 = Individual has _____ copies of chromosome # ________

16. Nondisjunction • Every cell in that baby’s body will have 3 copies of this chromosome instead of 2. • This condition is called TRISOMY • Trisomy 21 = Individual has __ copies of chromosome # ____.

17. Nondisjunction • Every cell in that baby’s body will have 3 copies of this chromosome instead of 2. • This condition is called TRISOMY • Trisomy 21 = Individual has 3 copies of chromosome # 21.

18. Chromosomal Mutations • Most chromosomal mutations are lethal • If the fetus survives: Tend to cause wide-spread abnormalities • Example: Down Syndrome

19. Down Syndrome • Cause: Nondisjunction of chromosome 21 • Three copies of chromosome 21 = “TRISOMY 21”

20. Trisomy 21 - Down Syndrome

21. Genetic Screening - Amniocentesis

22. KEY POINT #1 Too much or too little DNA is bad!

23. Let’s Review What are the 4 types of chromosomal aberrations? Which type of aberration is probably the most damaging?

24. Onto gene mutations!

25. Gene Mutations • Small scale: one geneis affected • Any change to the DNA sequence of a gene: Nucleotides/Bases may be added, missing, or changed

26. Gene Mutations: 2 Types Point Mutation Frameshift Mutation

27. Point Mutation • One base (A, T, C, or G) is substituted for another • Causes: Sickle-cell anemia • 3 Possible Consequences: • nonsense mutations: code for a stop, which can translate the protein • missense mutations: code for a different amino acid • silent mutations: code for the same amino acid

28. Frameshift Mutation • One or more bases (A, T, C, or G) are added or deleted • Causes: Cystic Fibrosis • Caused by: • Insertion: adding a base • Deletion: removing a base

29. Causes of Mutations • spontaneous • occur during DNA replication • Caused by MUTAGENS • physical, ex: radiation from UV rays, X-rays or extreme heat • or chemical (molecules that misplace base pairs or disrupt the helical shape of DNA).

30. Gene Mutations • KEY IDEA: A mutated gene will make a mutated protein • Mutant proteins are trouble! • They do not go where they are supposed to go • They do not do what they are supposed to do

31. Example: Sickle Cell Anemia Normal Red Blood Cell Sickle Red Blood Cell Red blood cells form an abnormal crescent shape Hemoglobin (protein) is abnormally shaped don't move easily through your blood vessels form clumps and get stuck in the blood vessels • Red blood cells shaped like a disc • Hemoglobin (protien) carries oxygen to all parts of the body

33. Example: Cystic Fibrosis (CF) • What is it? • Autosomal, recessive disorder • Symptoms • Thick mucus in the lungs and digestive track • Constant lung infections and impaired digestion

34. Cystic Fibrosis (CF) • Who gets it? • Anyone • Most common in Caucasians • Prevalence • 1 in ~3,000 Americans has CF • 1 in 23 white Americans carries the mutant allele!

35. Cause of Cystic Fibrosis (CF) • The “CFTR” gene is mutated • 3 base pairs are deleted • Mutant protein is missing an amino acid and cannot fold correctly vs

36. Normal CFTR protein:Ion channel in cell membrane

37. KEY POINT #2 Mutation of a gene = Mutant protein Dysfunctional proteins cause the symptoms of the disorder

38. Review • What are the two major types of genetic mutations? • How are chromosomal aberrations and gene mutations different? • What are the 4 types of chromosomal aberrations? • What are some types of gene mutations?