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 (meowing sounds, mental retardation)

7. Wolf-Hirschhorn syndrome (WHS) refers to a condition that is caused by a missing part (deletion) of the short arm of chromosome 4.

8. 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)

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

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

14. Nondisjunction Chromosomes FAIL TO SEPARATE during meiosis
Meiosis I Nondisjunction
Meiosis II Nondisjunction

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

16. Nondisjunction (in Meiosis II)

17. Fertilization

18. 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 # ________

19. 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 # ________

20. 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 # ____.

21. 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.

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

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

24. One in every 691 babies in the the United States is born with Down syndrome, making Down syndrome the most common genetic condition.
Short stature (height)
Low muscle tone
A short, wide neck.
Slanted eyes.
Irregularly shaped mouth and tongue.
Intellectual disability
Heart defects

25. Genetic Screening - Amniocentesis

26. Karyotypes
A pictorial display of metaphase chromosomes from a mitotic cell
Homologous chromosomes- pairs
Chromosomes pairs 1-22 are called autosomes
Chromosome pair 23 are called the sex chromosomes

27. Trisomy 21 - Down Syndrome

28. Klinefelter’s Syndrome
Due to nondisjunction
Chromosome makeup is XXY
Creates a sterile male

29. Turner’s Syndrome Due to nondisjunction
Monosomy- the condition in which there is a missing chromosome.
Sex chromosome make up is X only
Females that will not undergo puberty.

31. Edward’s Syndrome Due to nondisjunction
Extra number 18 chromosome (trisomy 18)
Traits: Low ears, kidney and heart defects

33. Patau’s Syndrome Extra number 13 chromosome (trisomy 13)
Traits: Deformed
eyes, ears and
lips, polydactyly
(extra fingers or
toes)

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

36. 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

37. Gene Mutations: 2 Types
Point Mutation
Frameshift Mutation

38. Point Mutation One base (A, T, C, or G) is substituted for another
Can Cause: 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

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

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

41. Gene Mutations
KEY IDEA: A mutated gene will make a mutated protein

42. Example: Sickle Cell Anemia
Normal Red Blood Cell
Red blood cells shaped like a disc
Hemoglobin (protien) carries oxygen to all parts of the body
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
Mutation located on Chromosome 11
Effects mostly African Americans

45. Example: Cystic Fibrosis (CF)
What is it?
Autosomal, recessive
disorder found on
Chromosome 7
Symptoms
Thick mucus in the lungs and digestive track
Constant lung infections and impaired digestion

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

47. 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

49. Albinism
Due to the lack of the pigment melanin (a protein) in the skin, eyes, and hair.

50. Hemophilia Disorder that is linked to the sex chromosomes
Missing a protein needed for the blood to clot

51. Tay-Sachs Disease
Inability to synthesize an enzyme that prevent lipid buildup in brain cells.
Causes the breakdown of nervous system

52. Phenylketonuria (PKU)
Inability to code for an enzyme needed for changing the amino acid phenylalanine to tyrosine.
Damages brain cells and causes mental retardation.

53. Duchenne Muscular Dystrophy
Linked to the sex chromosomes
Results in the progressive weakening and loss of skeletal muscle.

54. Colorblindness Carried on the X of the sex chromosomes.
Occurs more frequently in males than females.

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