1. Genetic Disorders

2. Inheritance of Genetic Traits
Genetic Disorders
Inheritance of Genetic Traits

3. Brief History
First there was Gregor Mendel, a monk who studied inherited characteristics. This was followed by Francis crick and James Watson who unraveled the DNA molecule. This has led us to understanding the human genome sequence

4. Gregor Mendel
1866
Gregor Mendel published the results of his investigations of the inheritance of "factors" in pea plants.

5. Rosalind Franklin
1950's.
Maurice Wilkins (1916- ), Rosalind Franklin ( ), Francis H. C. Crick (1916- ) of Britain and James D. Watson (1928- ) of the U.S. Discover chemical structure of DNA, starting a new branch of science--molecular biology. .

6. Watson and Crick
Watson and Crick made a model of the DNA molecule and proved that genes determine heredity

7. Arthur Kornberg
1957
Arthur Kornberg (1918- ) of the U.S. produced DNA in a test tube.

8. Genetic code
1966
The Genetic code was discovered; scientists are now able to predict characteristics by studying DNA. This leads to genetic engineering, genetic counseling.

9. Barbara McClintock
1983
Barbara McClintock ( ) of the U.S. was awarded the Nobel Prize for her discovery that genes are able to change position on chromosomes.

10. DNA Fingerprinting The late 1980's.
An international team of scientists began the project to map the human genome.
The first crime conviction based on DNA fingerprinting, in Portland Oregon.

11. Gene Therapy
1990.
Gene therapy was used on patients for the first time.

12. Dr. Kary Mullis
                           
1993
Dr. Kary Mullis discovered the PCR procedure, for which he was awarded the Nobel prize.

13. DNA Testing
                           
1995.
DNA testing in forensics cases gains fame in the O.J. Simpson trial.

14. Cloning Begins 1997. Dolly the sheep - the first adult animal clone.
                                     
1997.
Dolly the sheep - the first adult animal clone.

15. Human Genome Project
Imagine a world in which we will be able to treat diseases by altering our very genes‚ giving us new ones if ours are non-functional, changing bad genes for good ones. For the first time in our existence, we are closer to understanding just what we are. We now have the tools to make the whole world better through science ‚ the science of the human genome.

16. Mutations
Gene mutations can be either inherited from a parent or acquired. A hereditary mutation is a mistake that is present in the DNA of virtually all body cells. Hereditary mutations are also called germ line mutations because the gene change exists in the reproductive cells and can be passed from generation to generation, from parent to newborn. Moreover, the mutation is copied every time body cells divide

17. Mutations occur all the time in every cell in the body
Mutations occur all the time in every cell in the body. Each cell, however, has the remarkable ability to recognize mistakes and fix them before it passes them along to its descendants. But a cell's DNA repair mechanisms can fail, or be overwhelmed, or become less efficient with age. Over time, mistakes can accumulate.

18. extra, missing or mixed up chromosomes
Mistakes in Meiosis
extra, missing or mixed up chromosomes

19. Autosomal Aneuploidy having an unusual number of chromosomes 1-22
usually fatal
Trisomy – have three of a particular autosome instead of just two results from nondisjunction (homologous chromosomes fail to separate)
Examples:
1. trisomy 8
2. trisomy 13 (Patau syndrome)
3. trisomy 18 (Edward syndrome)
4. trisomy 21 (Down syndrome)

20. How to Study aneuploidy:
take sample cells from fetus & photograph metaphase chromosomes – line them up according to length & location of centromere = karyotype

21. Trisomy 13 Patau’s Syndrome
An individual with full trisomy 13 at age 7 years (survival beyond the first year is uncommon). 
He is deaf and legally blind

22. Edward’s Syndrome trisomy-18
1/8000 live births
Possible Malformations:
* Back part of head may be prominent
* Short eyelids
* Small mouth and unusually small jaw
* A small head
* Fold of the eyelid in the lateral corner of the eye
* Low set malformed ears

23. Trisomy-21 Three chromosomes in the 21st pair, and 47 total chromsomes
Also called Down Syndrome
Leads to physical defects and mental retardation

24. (Down Syndrome) Trisomy 21 Decreased muscle tone at birth
Separated sutures (joints between the bones of the skull)
Asymmetrical or odd-shaped skull
Round head with flat area at the back of the head
Small skull
Upward slanting eyes
Small mouth with protruding tongue (see tongue problems)
Broad short hands
Single crease on the palm (see below)
Retarded growth and development
Delayed mental and social skills (mental retardation)

25. Down’s Syndrome Caused by non-disjunction of the 21st chromosome.
This means that the individual has a trisomy (3 – 2lst chromosomes).

26. Down’s Syndrome or Trisomy 21

27. Symptoms of Down Syndrome
Upward slant to eyes.
Small ears that fold over at the top.
Small, flattened nose.
Small mouth, making tongue appear large.
Short neck.
Small hands with short fingers.

28. Symptoms of Down Syndrome
Low muscle tone.
Single deep crease across center of palm.
Looseness of joints.
Small skin folds at the inner corners of the eyes.
Excessive space between first and second toe.
In addition, down syndrome always involves some degree of mental retardation, from mild to severe. In most cases, the mental retardation is mild to moderate.

29. sex chromosome aneuploidy
missing or extra sex chromosome(s)
Examples:
1. Turner Syndrome - XO
 females who lack ovaries & sex characteristics; short & sterile
2. Klinefelter Syndrome - XXY
 taller, longer limbs, sterile, some exhibit mental retardation
3. XYY male – 1 in every 1000; normal, fertile, taller than average

30. Turner Syndrome - XO

31. Turner’s
Turner syndrome is associated with underdeveloped ovaries, short stature, webbed, and is only in women.
Bull neck, and broad chest. Individuals are sterile, and lack expected secondary sexual characteristics.
Mental retardation typically not evident.
Chromosomal or monogenic?

32. Turner’s Syndrome

33. Klinefelter Syndrome - XXY

34. Kleinfelter’s syndrome (or Klinefleter’s)
Disorder occurring due to nondisjunction of the X chromosome.
The Sperm containing both X and Y combines with an egg containing the X, results in a male child.
The egg may contribute the extra X chromosome.

35. XXY
Males with some development of breast tissue normally seen in females.
Little body hair is present, and such person are typically tall, have small testes.
Infertility results from absent sperm.
Evidence of mental retardation may or may not be present.

36. www. narragansett. k12. ri. us/NHS/. /mrreis/. /Genetic%20Disorders

37. www. narragansett. k12. ri. us/NHS/. /mrreis/. /Genetic%20Disorders

38. XYY male
Two men, one taller than the other. (c) Dorling Kindersley

39. A. Dominant Autosomal Heredity
Huntington’s disease – a rare genetic disorder caused by a dominant gene
 progressive degeneration of the nervous system causes uncontrolled jerky movements & mental deterioration
 no effective treatment exists
 passed on because symptoms don’t occur until 30-50, after they have children
 if you are at risk, you can find out if you are a carrier with a biochemical test

40. Huntington’s Disease
Huntington's disease (HD) is an inherited, degenerative brain disorder which results in an eventual loss of both mental and physical control. The disease is also known as Huntington's chorea. Chorea means "dance-like movements" and refers to the uncontrolled motions often associated with the disease.

41. www. narragansett. k12. ri. us/NHS/. /mrreis/. /Genetic%20Disorders

42. www. narragansett. k12. ri. us/NHS/. /mrreis/. /Genetic%20Disorders

43. Huntington’s
Looking back at the pedigree chart is Huntington’s dominant or recessive?
Scientists have discovered that the abnormal protein produced by the Huntington's disease gene, which contains an elongated stretch of amino acids called glutamines, binds more tightly to HAP-1 than the normal protein does.

44. Huntington's disease (HD) may be rare but among those who grew up in the '60s this disease is well known --- folk singer Woody Guthrie died at age 55 from the genetic disorder. Guthrie was the father of the well-known peace-and-love era hippie singer-songwriter Arlo Guthrie most famous for Alice's Restaurant.
Woody Guthrie inherited the progressive neurodegenerative disease from his mother and passed it on to two of his children. Their slow fatal declines were described by their caregiver as "a descent into hell." With the onset of HD a patient suffers years of physical and mental deterioration with attendant psychiatric problems leading eventually to death.
Because HD is a dominant genetic disease, children with an affected parent have a 50/50 chance of inheriting the fatal genetic disorder. Read more: 

45. B. Recessive Autosomal Heredity
most genetic disorders caused this way; rare except in some ethnic groups

46. 1. cystic fibrosis most common lethal genetic disorder among Americans
1 in 20 carry the recessive allele; 1 in has it
thick mucous in lungs makes breathing difficult; frequent lung infections
thick mucous also slows the secretion of some digestive enzymes
physical therapy, special diets, & new drug therapies have raised average life span

47. Physiotherapy for cystic fibrosis sufferer. (c) Dorling Kindersley

48. 2. sickle-cell anemia a blood disorder
most common in black Americans (Africa) or white Americans (Mediterranean Sea)
red blood cells are shaped like a sickle or half moon – can clog blood vessels
 rbc’s have a shorter life span – people suffer from anemia
hemoglobin protein in these cells differs from normal by one amino acid
treatments include transfusions & drug therapy
hetero’s can show signs if oxygen availability is low

49. Cystic Fibrosis (CF) Monogenic
Cause: deletion of only 3 bases on chromosome 7
Fluid in lungs, potential respiratory failure
Common among Caucasians…1 in 20 are carriers
Therefore is it dominant or recessive?

51. Sickle Cell Anemia
An inherited, chronic disease in which the red blood cells, normally disc-shaped, become crescent shaped. As a result, they function abnormally and cause small blood clots. These clots give rise to recurrent painful episodes called "sickle cell pain crises".

52. Sickle Cell
Sickle cell disease is most commonly found in African American populations.  This disease was discovered over 80 years ago, but has not been given the attention it deserves.

53. 3. Tay-Sachs disease affects the nervous system
missing an enzyme that normally breaks down a lipid produced & stored in the central
nervous system & it accumulates in the cells
results in blindness, progressive loss of movement & mental deterioration
symptoms occur within the first year of life & result in death by age 5; no treatment
allele common in PA Dutch

54. Tay-Sachs disease Monogenic, autosomal recessive
Central nervous system degrades, ultimately causing death.
Most common among people of Jewish, eastern Europe descent.

55. 4. phenylketonuria
is a treatable genetic disorder (Norway, Sweden)
absence of an enzyme that converts one amino acid, phenylalanine, to tyrosine
phenylalanine accumulates & can cause severe damage to the central nervous system
newborns appear normal since mother’s normal enzyme level prevents accumulation,
but when newborn begins drinking milk (high in phenylalanine) accumulation begins
PKU tests are now preformed on all newborns a few days after birth to prevent retardation

56. Phenylketonuria or PKU
People with PKU cannot consume any product that contains aspartame.
PKU is a metabolic disorder that results when the PKU gene is inherited from both parents (recessive or dominant? Monogenic or chromosomal?)
Caused by a deficiency of an enzyme which is necessary for proper metabolism of an amino acid called phenylalanine.

57. PKU
Phenylalanine is an essential amino acid and is found in nearly all foods which contain protein, dairy products, nuts, beans, tofu… etc.
A low protein diet must be followed.
Brain damage can result if the diet is not followed causing mental retardation…and mousy body odor (phenylacetic acid is in sweat).

58. PKU

59. Phenylalanine. Free diet

60. Even More Genetic Disorders:

61. Achondroplasia (dwarfism)
Symptoms
Absent or delayed sexual development in an adolescent
Excessive thirst with excessive urination
Headaches
Increased urine volume
Short stature -- below 5th percentile on a standardized growth chart, an adult less than 5 feet tall
Slow growth before age 5
Slowed or absent increase in height
Short person with short limbs, with large head and prominent forehead. (c) Dorling Kindersley

62. Achondroplasia (a.k.a. dwarfism)
Monogenic, autosomal
Carriers express genes, therefore, is it dominant or recessive?
There is also a disease called gigantism (Andre the Giant)

63. Fragile X Syndrome Overview
Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited mental retardation in males and a significant cause of mental retardation in females.
Symptoms
Mental retardation
Large testicles (macro-orchidism) after the beginning of puberty
Large body size
Tendency to avoid eye contact
Hyperactive behavior
Large forehead or ears with a prominent jaw
Grey haired man with prominent chin. (c) Dorling Kindersley

64. Albinism
Albinism is a congenital absence of normal pigmentation. It is characterized by partial or total lack of melanin pigment in the eyes, skin and hair. People who have this condition have visual difficulties like hypersensitivity to bright light and glare and many others.

65. Albinism
Patients are unable to produce skin or eye pigments, and thus are light-sensitive
Autosomal recessive
Therefore, is it monogenic or chromosomal?

66. Galactosemia

67. Cri-du-Chat Symptoms Cry that is high-pitched and sounds like a cat
Downward slant to the eyes
Low birth weight and slow growth
Low-set or abnormally shaped ears
Mental retardation
Partial webbing or fusing of fingers or toes
Single line in the palm of the hand (simian crease)
Skin tags just in front of the ear
Slow or incomplete development of motor skills
Small head (microcephaly)
Small jaw (micrognathia)
Wide-set eyes

68. Williams Syndrome
Williams syndrome is a rare genetic disorder that can lead to problems with development
affects a child's growth, physical appearance, and cognitive development
missing genetic material from chromosome 7, including the gene elastin - gives blood vessels the stretchiness and strength
The most common symptoms of Williams syndrome are mental retardation, heart defects, and unusual facial features (small upturned nose, wide mouth, full lips, small chin, widely spaced teeth).
People with this syndrome also exhibit characteristic behaviors, such as hypersensitivity to loud noises and an overly outgoing personality.

69. Resources:
100/humgenetics2.html
03/human-genetic-disorder-part-i.html
Genetic Disorders narragansett.k12.ri.us/NHS PowerPoint
Genetic Disorders faculty.ccc.edu/jminarcik/Ch5.ppt

70. Hemophilia, the royal disease
Hemophilia is the oldest known hereditary bleeding disorder.
Caused by a recessive gene on the X chromosome.
There are about 20,000 hemophilia patients in the United States.
One can bleed to death with small cuts.
The severity of hemophilia is related to the amount of the clotting factor in the blood. About 70% of hemophilia patients have less than one percent of the normal amount and, thus, have severe hemophilia.

71. X-linked Inheritance pedigree chart

72. Color Blindness Cause: x-linked recessive
1/10 males have, 1/100 females have. Why the difference?
Individuals are unable to distinguish shades of red-green.
Are you color blind?
                                          

73. www. narragansett. k12. ri. us/NHS/. /mrreis/. /Genetic%20Disorders

74. Muscular Dystrophy
What Is Muscular Dystrophy? Muscular dystrophy is a disease in which the muscles of the body get weaker and weaker and slowly stop working because of a lack of a certain protein (see the relationship to genetics?)
Can be passed on by one or both parents, depending on the form of MD (therefore is autosomal dominant and recessive)

75. ALS (Amyotrophic Lateral Sclerosis, or Lou Gehrig’s disease)

76. the disease strikes people between the ages of 40 and 70, and as many as 30,000 Americans have the disease at any given time
This monogenic mutation is believed to make a defective protein that is toxic to motor nerve cells.
A common first symptom is a painless weakness in a hand, foot, arm or leg, other early symptoms include speech swallowing or walking difficulty

77. Adenoleukodystrophy
ALD) is a rare, inherited metabolic disorder that afflicts the young boy Lorenzo Odone, whose story is told in the 1993 film 'Lorenzo's oil'. In this disease the fatty covering (myelin sheath) on nerve fibers in the brain is lost, and the adrenal gland degenerates, leading to progressive neurological disability and death.

78. Lorenzo’s Oil
Their invention, Lorenzo's Oil, has been adopted as the therapy of choice for ALD by major neurological institutes the world over.

79. Lorenzo Odone
The oil came too late to stop his son from developing the symptoms must be hard to bear. Lorenzo lost most of his bodily functions and has been bedridden for 18 years.

80. Diabetes Disease in which the body does
not produce or properly use insulin.
Insulin is a hormone that is needed to convert sugar, starches, and other food into energy needed for daily life.
Genetic mutation can lead to Type 1 diabetes, but no one sure if relative to a specific gene

81. Diabetes Warning signs
Type 1 reveals itself in childhood, Type 2 can be made worse from excessive lifestyle
Warning signs
Extreme thirst
Blurry vision from time to time
Frequent urination
Unusual fatigue or drowsiness
Unexplained weight loss
Diabetes is the leading cause of kidney failure, blindness, and amputation in adults, and can also lead to heart disease.

82. The very tragic disease… hairy ears
Y-linked trait, which are rare
symptoms…hairy ears
Only 1 cure known….

83. Summary of Genetic Disorders