Human Genetic Disorders

1. Human Genetic Disorders Biology

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

3. 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

4. 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

5. 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.

6. Family Pedigrees

7. Down Syndrome • Caused by Trisomy 21 • Symptoms: • Mental retardation • 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)

8. Edward Syndrome • Caused by Trisomy 18 • Symptoms: • Mental and physical retardation • Skull and facial abnormalities • Defects in all organ systems • Poor muscle tone • Average life expectancy: 2-4 months

9. Patau Syndrome • Caused by Trisomy 13 • Symptoms: • Mental and physical retardation • Skull and facial abnormalities • Defects in all organ systems • Cleft lip & large triangular nose • Extra digits • Average life expectancy: 6 months (but ½ die in the first month)

10. 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

11. 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)

12. 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)

13. 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

14. 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

15. 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

16. 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

17. Sickle-Cell Anemia Photo

18. 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

19. 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?

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

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

22. 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