1. Human Genetic Disorders

2. Autosomal Recessive Disorders
Requires the inheritance of two recessive alleles
Error found on chromosomes

3. Albinism
Inability to make melanin which gives pigmentation to hair, eyes, and skin
Mutation in the tyrosinase gene on chromosome #11
Tyrosinase is an enzyme that functions in the production of melanin

4. Problems Visual Problems that cannot be corrected with glasses
Sunburn VERY easily
Life expectancy is normal
Incidence is 1 in 17,000 births. 18,000 cases in USA

5. Cystic Fibrosis
Results in thick, sticky secretions in the respiration and digestive tract
Mutation in the gene for the transmembrane protein that acts as a channel for chloride ions
This gene is located on chromosome #7

6. Cystic Fibrosis 3,200 white babies born each year with CF
30,000 Americans live with CF
12 million Americans are carriers
1/20 European Americans are carriers

7. Cystic Fibrosis & Cholera
Cholera produces a toxin that opens chloride channels in the small intestine. This causes the often fatal diarrhea and dehydration in cholera patients.
In Europe, cholera epidemics have claimed millions of lives
People heterozygous for CF have fewer chloride channels and are resistant to cholera.
This explains the prevalence in European Americans

8. Celine Dion’s niece died of cystic fibrosis
Celine Dion’s niece died of cystic fibrosis. Since that time she has been a major spokesperson/fundraiser for cystic fibrosis. Her song, Fly, was written to honor the death of her niece.

9. Phenylketonuria (PKU)
One of the most common causes of mental retardation
Mutation in gene for the enzyme phenylalanine hydroxylase on chromosome #12
This enzyme converts the amino acid phenylalanine to the amino acid tyrosine

10. Phenylketonuria (PKU)
If phenylalanine is not broken down, the build up of this amino acid causes brain dysfunction and mental retardation
All babies in the US are screen for PKU and if put on a phenylalanine restricted diet will not develop mental retardation.
1 in 4,500 people from Ireland have PKU
1 in 8,000 American Caucasians have PKU
The heterozygous condition is believed to give protection against fungal infections in pregnant mothers. The original mutation is believed to be Celtic (northern European) in origin.

11. Sickle Cell Anemia
A blood disorder that results in a change in shape of the red blood cell from round to “sickle” shaped. This causes clogging of capillaries and tissues are deprived of oxygen.
Mutation in the beta chain of the hemoglobin protein gene found on chromosome #11.

12. Sickle Cell Anemia Most prevalent in persons of African descent.
1/12 African Americans are carriers of the disease.
Heterozygotes have protection from malaria.

14. Tay Sach’s Disease
A fatal disease that results from the build up of fatty acids around nerves of the central nervous system (brain & spinal cord)
Caused by the lack of the enzyme hexosaminidase A which is responsible for degrading lipids (fats)
The gene for this protein is located on chromosome #15
Interesting—this enzyme is actually normally found in the lysosomes and is a part of the normal cell recycling system.

15. Problems
Babies appear normal at first. After a few months they develop developmental problems, go blind, deaf, and become paralyzed.
They are diagnosed by a “cherry-red” spot in the eye
They die by the age of five.

16. Prevalence
Tay-Sachs is most common in descendents of Central & Eastern European Jews
About 1/30 American Jews are carriers of Tay-Sachs disease

17. Autosomal Dominant Disorders
Require the inheritance of only one copy of the allele
Found on chromosomes

18. Achondroplasia The most common form of dwarfism
Caused by a mutation in the gene for the Fibroblast growth factor receptor 3 protein
This protein functions in normal bone growth
This gene is found on chromosome #4

19. Achondroplasia
Because dwarfism was widely recorded in Egyptian art, it is considered the oldest recorded birth defect
1/25,000 births result in achondroplasia
Over 80% of these births are to parents of normal height; they are the result of a spontaneous mutation
It is often hypothesized that the pharoahs were dwarfs—that this rare stature was a sign from the gods.

20. Huntington’s Disease
Genetically programmed degeneration of brain cells causing uncontrolled movements, loss of mental faculties, and emotional disturbance
Caused by an abnormal gene for the protein huntingtin. Huntingtin is believed to function in normal brain activity.
The gene is located on chromosome #4.

21. Huntington’s Disease
In the normal gene for huntingtin, there is a section of DNA with up to 28 CAG codons repeated. (This codes for glutamine.)
In the abnormal gene, there is 40 or more repeats of the CAG codon and subsequently, a longer chain of glutamine in the protein.
Chains of glutamine are known for causing other neurological disorders.

22. Huntington’s Disease
Symptoms usually do not appear until a person is in their 40’s
There are currently 1,500 people in the US with Huntington’s Disease
It affects males and females and all races at the same rate

23. Marfan Syndrome
Characterized by problems with the skeleton, eyes, heart, and blood vessels.
Caused by a mutation in the gene for the protein fibrillin. This protein is essential for the formation of elastic fibers in the connective tissue.
This gene is located on chromosome #15.
Interesting—there is not a single mutation or couple of mutations found in families with this disorder—every family tends to have its “own” mutation.

24. Marfan Syndrome
People with Marfan characteristically are tall with very long limbs and fingers
It is believed that Abraham Lincoln had Marfan Syndrome
Many times people do not know they have the disease and yet are susceptible to aortic rupture
1/5,000 people in the US have Marfan Syndrome
Olympic star volleyball player Flo Hyman died of aortic rupture in Florida State University basketball player Ronaldo Pierce died of aortic rupture in Both had Marfan Syndrome.

26. Neurofibromatosis
Results in the growth of noncancerous tumors along nerves
Caused by a mutation in the gene for neurofibronin which is believed to act in tumor suppression. Therefore, if it is mutated, tumors are the result.
This gene is located on chromosome #17.

27. Neurofibromatosis
People afflicted have tumors that grow on their skin and can have bone deformity
1/4,000 babies in the US are born with neurofibromatosis
30 – 50% of the cases arise spontaneously
People usually lead a normal life
Interesting---this was once thought to be the disease of the “Elephant Man”. However, now that is diagnosed as Proteus syndrome

28. Osteogenesis Imperfecta
Characterized by bones that break frequently, often from no apparent cause
Results from abnormal production of collagen, the protein that is the primary constituent of the connective tissue (BOND IS A CONNECTIVE TISSUE!)
The gene for the alpha chain of collagen is located on chromosome #17, and the gene for the beta chain is on chromosome #7.
Often referred to as the “brittle bone” disease

29. Osteogenesis Imperfecta
It is estimated there are 20,000 – 50,000 people in the US with OI
Many cases are the result of spontaneous mutations
The symptoms vary widely but with proper care, good diet, exercise, etc. people with OI can lead normal lives

30. X-Linked Recessive Females have to inherit two copies of the gene
Males have to inherit one copy on the X from their mother

31. Duchenne Muscular Dystrophy
Characterized by progressive muscle weakness and wasting beginning early in life
Caused by a mutation in the gene for dystrophin
Dystrophin is the structural protein that provides support for muscle cells
No dystrophin—muscles do not work

32. Duchenne Muscular Dystrophy
1/3,500 boys worldwide have DMD
Most are wheelchair bound by 10 and die by age 20
Eventually cardiac and respiratory muscles waste away

33. Fragile X Syndrome Most common cause of genetic mental impairment
Mutation in the Fragile X Mental retardation protein believed to help brain cells develop & function normally

34. Fragile X Syndrome
In the promoter region for the FMR1 gene, there are CGG repeats
In the normal gene there are 6 – 40 repeats
In the abnormal gene there may be hundreds of repeats
The more CGG is repeated the more severe the disease
Heterozygous females make enough FMR to have normal intelligence
1/2000 males have Fragile X; 1/4,000 females

35. Fragile X

36. Hemophilia
Disorder resulting in improper blood clotting from cuts or from internal injuries
It is a result of a mutation in the gene for Blood Clotting Factor VIII
This protein is involved in stopping the flow of blood out of vessels when they are ruptured

37. ROYAL Hemophilia

38. Hemophilia
About 18,000 people (almost all male) in the US have hemophilia
400 babies in the US each year are born with hemophilia
In the 1980’s approximately 10,000 children were infected with HIV because of transfusions for hemophilia
With proper treatment, hemophiliacs can live a normal life

39. Nondisjunction Disorders
Caused by an abnormal number of a particular chromosome

40. Down Syndrome
Trisomy 21
Low muscle tone, flat face, slanted eyes, abnormal shape and small size ears
Most have congenital heart defects
Suffer from mild to moderate mental retardation
With good care, most live to around age 55
1/800 to 1/1,000 live births result in Down Syndrome

41. Down Syndrome

42. Edward’s Syndrome Trisomy 18
Results in small jaw, low-set ears, malformation of the head, hands, feet; kidney and heart defects
30% of babies die in first month
Less than 10% survive first year
Occurs in 1/6,000 live births
Twice as many females are born with Edward’s as are males

43. Edward’s Syndrome

44. Klinefelter’s Syndrome
XXY
Men affected have enlarged breasts, small testes, sparse facial and body hair, and inability to produce sperm
Some have lower IQ, many are very tall with long arms & legs
These men live as long as healthy individuals
1/500 – 1/1,000 males in US have XXY
3,000 males are born yearly with XXY

45. Klinefelter’s Syndrome

46. Patau Syndrome Trisomy 13
Results in cleft palate, polydactyly, severe mental deficiency, heart defects, and other abnormalities
Average lifespan is 3 days
Only 1 in 20 children survive longer than 6 months
Least common of all survivable trisomies
Occurs in 1/8,000 – 1/12,000 births
Birth rate favors females

47. Patau Syndrome

48. Turner Syndrome Monosomy X
Inhibits sexual development and causes infertility
Females are usually short with webbed necks, drooping eyelids, bone development problems, and retarded secondary sex characteristics
IQ is usually normal
Occurs in 1/3,000 live births

49. Turner Syndrome