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. One or more genes are removed
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. Too much or too little DNA is bad!
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 gene is 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 shaped like a disc
Hemoglobin (protien) carries oxygen to all parts of the body
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

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?