Human Genetic Disorders

1. Key Concepts What are two major causes of genetic disorders in humans? How do geneticists trace the inheritance of traits? How are genetic disorders diagnosed and treated? Human Genetic Disorders

2. Key Terms • Genetic disorder • Karyotype • pedigree

3. Causes of Genetic Disorders • Genetic disorder – abnormal condition that a person inherits through genes or chromosomes • Some are caused by mutations in the DNA of genes • Others are caused by changes in the overall structure or number of chromosomes

4. What Can Go Wrong? • Nondisjunction (most deadly) • Improper separation of homologous chromosomes in meiosis I or chromatids in mieosis II or mitosis (at an early embryonic stage) • Results in too many or too few chromosomes in daughter cells • DNA mutations • More specific letter-changes in code • Results in the inability to make certain proteins

5. Cystic Fibrosis • Body produces abnormally thick mucus in the lungs and intestines • The thick mucus fills the lungs making it hard to breathe • Caused by recessive • allele on one chromosome that is the result of a mutation in which 3 base pairs are removed from a DNA molecule

6. Sickle- Cell Disease • Affects hemoglobin, protein in blood that carries O2 • When o2 concentrations are low blood cells have a sickle shape • The sickle shape can clog blood vessels and cannot carry as much O2 as normal shaped red blood cells • The allele is codominant with normal allele • A person with 2 sickle shaped alleles will have the disease • One allele and the person will produce both normal and sickle shaped cells. These people will not usually have symptoms of the disease

7. Hemophilia • A person’s blood clots • very slowly or not at all • Do not produce one of the proteins needed for normal blood clotting • Small bumps and bruises may cause internal bleeding that can’t be controlled • Caused by a recessive allele on the X chromosome • Sex-linked disorder – occurs more frequently in males

8. Nondisjunction Causes: • Aneuploidy: cells that have too many or too few chromosomes are aneuploid. • Monosomy: only 1 of a pair present • Trisomy: 3 instead of 2 present

9. Down SyndromeTrisomy 21 • Have an extra copy of chromosome 21 (instead of • a pair the person has 3 copies) • Most often occurs when chromosomes fail to separate properly during meiosis • Have some degree of Intellectual and Developmental Disabilities. • Heart defects are also common, but can be treated

10. Down Syndrome • Caused by Trisomy 21 • Symptoms: • Intellectual and Developmental Disabilities • Flattened face • Sparse, straight hair • Short stature • High risk of cardiac anomalies, leukemia, cataracts, and digestive blockages • Average life expectancy: 55 years (much longer than it used to be even just recently)

11. Karyotypes • Picture of all the chromosomes in a cell • Arranged in pairs • Can reveal whether a person has the correct number of chromosomes

12. Pedigrees • Chart used to trace the inheritance of traits in humans • Can track ordinary traits or a genetic disorder

13. Family Pedigrees

14. Family Pedigrees

15. Managing Genetic Disorders • Doctors used to only have Punnett Squares and pedigrees to help predict genetic disorders • Now they have tools such as karyotypes to help diagnose genetic disorders • People with genetic disorders can be helped through medical care, education, job training, and other methods

16. Genetic Testing • Amniocentesis and Chronic Villi Sampling • Sample of amniotic fluid or placenta • Karyotyping • Taking a picture of the chromosomes in a cell

17. Genetic Counseling • A couple with a family history of a genetic disorder can go to a genetic counselor for advice • Help couples understand their chances of having a child with a particular genetic disorder

18. Dealing with Genetic Disorders • Medical treatments help people with some disorders • Ex. Physical therapy helps remove mucus from the lungs of people with cystic fibrosis • Taking Folic Acid helps people with sickle-cell disease make more red blood cells • Education and job training helps people with Down Syndrome find work in a variety of places of employment

19. Incidence of Genetic Abnormalities • Maternal Age • At 25 years, 17% of eggs may have chromosomal abnormalities. At 40 years, up to 74% may contain abnormalities. • Spontaneous Abortion (Miscarriage) • Two-thirds of all pregnancies are lost. These miscarriages are called spontaneous abortions. • Genetic mutation causes an estimated 60% of these spontaneous abortions.

20. Sex Chromosome Abnormalities • Turners Syndrome (X0 - female) • 1 in 2000 • Infertile, sexually underdeveloped, short stature, narrow aorta, normal intelligence • Klinefelter Syndrome (XXY - male) • 1 in 1000 • Reduced sexual maturity, secondary sexual characteristics (breast swelling), no sperm production

21. Sex Chromosome Abnormalities • Triple X Syndrome (XXX – female) • 1 in 1500 • Slight IQ reduction, menstrual irregularities • Jacob Syndrome (XYY – male) • Incidence unknown (lack of diagnosis) • Tall, acne issues, speech/reading problems • Disproportionate number incarcerated • 96% are normal (most don’t realize they have this condition)

22. DNA Mutations • Cri du Chat Syndrome (cry of the cat) • Deletion on part of chromosome 5 • Fragile X • Repeated sequences of CCG on X chromosome • Normal = 6-50 copies • Carrier (males) = 50-230 copies • Disorder = more than 230 copies • Causes mental retardation (2nd behind only Down Syndrome)

23. Autosomal Recessive Disorders • Cystic Fibrosis (CF) • Mutation on chromosome 7 • Thick mucous develops in lungs and digestive tract • Difficulty breathing & lung infections • Most common lethal genetic disorder • 1 in 25 is a carrier • 1 in 2500 has disorder

24. More Autosomal Recessive • Tay Sachs Disease • Fatty substance builds up in neurons • Gradual paralysis and loss of nervous function by age 4-5 • Single defective enzyme • Heterozygote carriers (Hh) do not have disorder, but are resistant to Tuberculosis • Especially common in Jewish population (central and eastern European descent), up to 11% are carriers

25. More Autosomal Recessive • PKU (Phenylketonuria) • Can’t break down amino acid phenylalanine (missing critical enzyme) • Phenylalanine builds up and interferes with nervous system leading to mental retardation and even death • Early screening  phenylalanine restricted diet for children with disorder

26. More Autosomal Recessive • Sickle-Cell Anemia • Abnormality in hemoglobin (carries oxygen in our red blood cells) • Cells become sickle-shaped and clog blood vessels (painful) • Causes poor circulation, jaundice, anemia, and hemorrhaging • Heterozygote carriers (Hh) do not have disorder and are resistant to malaria • 8-10% of Africans (or descendants) are carriers

27. Sickle-Cell Anemia Photo

28. Autosomal Dominant Disorders • Neurofibromatosis (NF) • Could be “Elephant Man’s” disorder • As mild as tan spots on skin • Could cause severe deformities, tumors, even death • 1 in 3000 newborns • Mutation on chromosome 17

29. Autosomal Dominant Disorders • Huntington’s Disease • Brain cells degenerate, causing involuntary muscle jerks, slurred speach, loss of balance, mood swings, memory loss, incapacitation • Progressive: eventually causes death • Onset: 35-45 years old • Repeated sequences of AGC on chromosome 4 • Diagnostic test available, but no cure • Would you want to know?

30. X-Linked or Sex-Linked Traits • Traits located on X Chromosome • Males have them more often than females • They only have one X chromosome

31. X-Linked or Sex-Linked Traits • Colorblindness (3 types – Red/Green most common)

32. X-Linked or Sex-Linked Traits • Hemophilia • 1 in 1500 males • Lack a blood clotting factor • Can bleed to death from wounds or bruises (internal bleeding) • Duchenne Muscular Dystrophy • 1 in 5000 males • Muscular deterioration starts 3-5 years old • Wheelchair by 12, rarely survive past 20