Human Genetics: Genetic Disorders

1. Human Genetics:Genetic Disorders Ms. Y. Martinez LSHS 07-08

2. Genes and the Environment  • The phenotype of an organism is only partly determined by its genotype. • Many traits are strongly influenced by environmental, or nongenetic, factors, including nutrition, exercise and sunlight. • For example, nutritional improvements in the United States and Europe have increased the average height of these populations about 10 centimeters over their average height in the 1800s.

3. Human Genetic Disorders • Most of the time, the mechanisms that separate human chromosomes in meiosis work very well, but every now and then something goes wrong.

4. The most common error in meiosis occurs when homologous chromosomes fail to separate. This is known as nondisjunction, which means “not coming apart.” • If nondisjunction occurs, abnormal numbers of chromosomes may find their way into gametes, and a disorder of chromosome numbers may result.

5. At the end of meiosis, the chromosomes have failed to separate and the gametes have an UNEQUAL number of chromosomes

6. After nondisjunction occurs and a gamete has one EXTRA chromosome, a Trisomic human genetic disorder can result. • After nondisjunction occurs and a gamete has one LESS chromosome, a MONOSOMIC human genetic disorder can result.

7. Trisomy Disorders • Remember 2n = 46 • In a trisomy disorder, a gamete has gained an EXTRA chromosome • So, a trisomic individual has 2n = 47

8. Trisomy Disorders • Trisomy 21 (Down or Down’s Syndrome) • Klinefelter (or Klinefelter’s) Syndrome (Males only, XXY Trisomy) 2n = 47

9. Trisomy 21, Down Syndrome • Individuals have an extra 21st chromosome • Usually occurs once in every 800 births

10. People with Down Syndrome

11. Characteristics • Round face • Extra 21st chromosome • Short fingers • Cupped ear • Protruding tongue • Mental deficiency

12. Simian Crease in the hand • Nondisjunction is the cause

13. Incidence of Down Syndrome in Newborns (Hook, et al., 1988) Maternal Age Incidence • 20 – 24 1 : 1400 • 25 – 29 1 : 1100 • 30 - 34 1 : 700 • 1 : 350 • 1 : 225 • 39 1 : 140 • 41 1: 85 • 43 1: 50 • 45+1 :25

14. Klinefelter Syndrome, XXY Trisomy • Individuals have an extra “X” sex chromosome • Usually occurs once in every 1080 births

15. A male with Klinefelter Syndrome

16. Male reproductive cells do not undergo meiosis (sterile) • Only 40% have breast development • Intelligence is less than normal • Nondisjunction is the cause

17. Monosomy Disorders • Remember 2n = 46 • In a monosomy disorder, a gamete has LOST a chromosome • So, a monosomic individual has 2n = 45

18. Monosomy Disorders • Turner Syndrome, XO (Females Only) • OR • Turner Syndrome , X (Females only) 2n = 45

19. Turner Syndrome, X or XO • Individuals have only ONE “X” sex chromosome • Usually occurs once in every 5000 births

20. A female with Turner Syndrome

21. Female reproductive cells do not undergo meiosis (sterile) • Has webbing of the neck • Intelligence is less than normal • Nondisjunction is the cause

22. Autosomal Dominant Disorders (ex RR, Rr) • Autosomal dominant is one of several ways that a trait or disorder can be passed down through families. • If a disease is autosomal dominant, it means you only need to get the abnormal gene from one parent in order for you to inherit the disease. One of the parents may often have the disease.

23. Examples of Autosomal Dominant Disorders (ex RR, Rr) • Huntington’s Disease • Achondroplasia • Polydactyly • Marfan Syndrome

24. Huntington’s Disease, DD or Dd • Huntington's disease causes a progressive loss of muscle control and mental function until death occurs. • People who have this disease generally show no symptoms until they are in their thirties or older, when the gradual damage to the nervous system begins.

25. Achondroplasia, DD or Dd

26. Most people with achondroplasia are born to parents of average height, following a genetic change - usually in the sperm. • This particular change - or mutation - occurs occasionally when the DNA is copied in cells that multiply to make the sperm. • The mutation that causes achondroplasia is a single change in the letters of the DNA code of the FGFR-3 gene.

27. Characteristics • short stature • short arms • short legs • a large head

28. Polydactyly, DD or Dd • Polydactyly refers to extra digits - in the hand, extra fingers or thumbs.

29. Marfan Syndrome, DD or Dd • Marfan syndrome is a disorder that affects connective tissue. • Connective tissues are proteins that support skin, bones, blood vessels and other organs.

30. Characteristics • very tall • Thin • Double jointed • heart and blood vessel problems • a weak in the aorta

31. President Abraham Lincoln was thought to have Marfan Syndrome. • What do you think?

32. Autosomal Recessive Disorders (ex rr) • Autosomal recessive is one of several ways that a trait, disorder, or disease can be passed down through families. • An autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop.

33. Autosomal Recessive Disorders (ex rr) • Phenylketonuria (fen-ul-ket-oh-NOOR-ee-uh), , PKU • Cystic Fibrosis • Tay-Sachs Disease • Sickle-cell Anemia • Albinism

34. Phenylketonuria, PKU, (ex rr) • Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. • Phenylalanine is an amino acid found in milk and many other foods. • If it goes untreated, it causes “mental retardation.” (http://www.marchofdimes.com/professionals/14332_1219.asp)

35. Cystic Fibrosis, (ex rr) • Is a common genetic disease that is most common among people whose ancestors came from Northern Europe. • The disease is caused by a recessive allele on chromosome 7. • Children with cystic fibrosis have serious digestive problems. In addition, they produce a thick, heavy mucus that clogs their lungs and breathing passageways.

38. Tay-Sachs Disease, (ex rr) • Is caused by an allele found mostly in Jewish families of central and eastern European ancestry. • Tay-Sachs disease results in nervous system breakdown and death in the first few years of life. • Although there no treatment for Tay-Sachs disease.

39. Sickle Cell Disease • Is a common genetic disorder found in African Americans. • Is characterized by the bent and twisted shape of the red blood cells. • These sickle-shaped red blood cells tend to get stuck in the capillaries, the narrowest blood vessels in the body. • As a result, blood stops moving through these vessels, damaging cells, tissues, and organs. • Sickle cell disease produces physical weakness and damage to the brain, heart, and spleen. In some cases, it may be fatal.

40. Hemoglobin is the protein in red blood cells that carries oxygen. • The normal allele for the gene differs little from the sickle cell allele—just one DNA base is changed. • This change substitutes the amino acid valine for glutamic acid. • As a result, the abnormal hemoglobin is somewhat less soluble than normal hemoglobin.

41. Albinism, (ex rr)

42. Albinism, (ex rr) • Is an inherited condition present at birth, characterized by a lack of pigment that normally gives color to the skin, hair, and eyes. • Many types of albinism exist. • The condition, which is found in all races, may be accompanied by eye problems and may lead to skin cancer later in life.

43. Sex-Linked Recessive Disorders(ex XrXr or XrY) • Sex-linked diseases are inherited through one of the "sex chromosomes" -- the X or Y chromosomes. • Because these chromosomes determine sex, genes located on them are said to be sex-linked genes. • Many sex-linked genes are found on the X chromosome. • Are found more often in Males (XY makeup)

44. If mom is a carrier and dad is normal, what chance will: • their daughters be carriers?___ • their daughters express the disorder?____ • their sons express the disorder?____ • their sons be carriers of the disorder?____

45. Colorblindness, XrXr or XrY • The gene associated with color vision is located on the X chromosome. • In males, a defective version of this gene produces colorblindness, an inability to distinguish certain colors. • The most common form of this disorder, red-green colorblindness, is found in about 1 in 10 males in the United States. • Among females, however, colorblindness is rare—only about 1 female in 100 has colorblindness. Why the difference?

46. A non-colorblind individual will be able to see the number. A colorblind individual will not.

47. A colorblind individual will not see the green leaf. • A non-colorblind individual will it.

48. Hemophilia, XrXr or XrY • In hemophilia, a protein necessary for normal blood clotting is missing. • About 1 in 10,000 males is born with a form of hemophilia. • People with hemophilia can bleed to death from minor cuts and may suffer internal bleeding from bumps or bruises. • Hemophilia can be treated by injections of normal clotting proteins, which are now produced using recombinant DNA.

49. Czar Nicholas II of Russia and his family, photographed c. 1916, showing his wife Alexandra (who was a carrier of hemophilia), his four daughters, and (in the foreground) his son Alexis, perhaps the most famous European royal with hemophilia.

50. Duchenne Muscular Dystrophy, XrXr or XrY • Duchenne muscular dystrophy (DIS-truh-fee) is a sex-linked disorder that results in the progressive weakening and loss of skeletal muscle. • In the United States, one out of every 3000 males is born with this condition.