Genetics

1. Genetics Chapter 14: Human Genetics

2. Sickle Cell Anemia • Recessive • Defective Hemoglobin on RBCs • Anemia (loss of blood cells) • Damage to brain, heart, lungs • Primarily in African Americans; 1/10 in US is a carrier

3. Cystic Fibrosis • Recessive • Point mutation stops production of a protein in the lungs and pancreas • Prevents cells from transporting Cl- ions out of the cell • Lung Congestion • Abnormally thick mucus lining in lungs • Chronic Bacterial Infections (pneumonia) • Treated with antibiotics, lung transplant, and new genetic engineering treatments

4. Tay Sachs • Recessive • Lack of enzyme hexosaminidase A (hex A), which breaks down fatty acids in brain in nervous tissue • Symptoms appear at 4-6 months • Death by 5 years • Found primarily in those descendants of Ashkenazi Jews • 1/30 American Jews carry the gene

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

6. Huntington's Disorder • Autosomal- Dominant • Lethal • Begins around ages 35-45 • First symptoms; mild forgetfulness and irritability • Lose control over muscles • Genetic Marker: short section of DNA that has a close association with a known gene • Presence of gene marker can indicate the presence of huntington’s allele • People with marker have 90% chance of developing Huntington’s • Gene Marker and gene so close on chromosome rarely separated by crossing over during meiosis

7. 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)

8. Marfan's Syndrome • Dominant Disorder • 1/20,000 people • Believed to be caused by a mutation in the fibrillin gene on chromosome 15 • Connective Tissue defects • Dislocation of lens in eye • Rupture of aorta (weak vessel walls) • Arachnodactyly – “spider fingers” • Elongated body, face • Pectus Excavatum (caved in chest)

9. Marfan's Syndrome • Abraham Lincoln? • Descendents of Lincoln’s great-great grandfather (8th generation) diagnosed with Marfan’s • Lincoln could have had a mild form of Marfan’s • Should we test Lincoln’s DNA?

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

11. 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

12. Phenylketonuria (PKU) • Do not contain enzyme phenylalanine hydroxlyase (PAH) that breaks down amino acid phenylalanine into amino acid tyrosine • Phenylalanine builds up in brain • Toxic to central nervous system (CNS) • Mental Retardation • Tested at birth • PKU – 1/10,000 • U.S.  1/50 carry PKU allele • Regulated by Strict diet • Low protein: no meat, eggs, dairy • No Aspartame: sugar substitute sold as Equal or NutraSweet • Contains amino acid phenylalanine – 50%

13. Sex-Influenced Traits • Sex- Influenced: • Presence of male or female hormones influences the expression of the trait • Males and females with the same genotype will have different phenoypes • Ex: baldness; B=baldness, B’=normal hair • BB=bald (male/female) • B’B’=normal hair (male/female) • BB’= bald (male) normal (female)

14. Sex Linkage • Presence of gene on a sex chromosome (X or y) • X chromosome is larger than y  more genes carried on the X • X-Linked Genes:genes found on X chromosome • Appear mostly in males • Only one copy of X; nothing to counteract “bad gene” • Females would need two copies to express trait

15. Colorblindness • X-linked recessive • Cannot distinguish between different colors • Most common type is red/green colorblindness • Heterozygous females have mosaic retinas in which they have patches of color vision • Heterozygous female is considered a carrier

16. Hemophilia • X-linked recessive • Most Common in males • “Bleeder’s Disease” • Missing clotting factor • Bleeding spontaneously and in joints • Queen Victoria: descendents affected with hemophilia • Alexei Romanov

17. Duchenne Muscular Dystrophy • X-linked recessive • Most Common in males • 1/3500 • Muscle Enlargement • Dystrophin • Protein that provides support for the cell; without it, cell enlarges and explodes

18. Adrenoleukodystrophy • X-linked recessive • Most Common in males • “Lorenzo’s Oil” • Degradation of myelin sheath surrounding nerves (insulation) • Current News: • Oil not as effective as previously thought • Cholesterol lowering drug, Lovastatin seems to work • Bone Marrow Transplants work in some cases • Lorenzo Odone turned 27 on May 29, 2005 (Still completely paralyzed)

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

20. Karyotype • Karyotype: chromosomes are stained and photographed under the microscope, cut from photo and arranged by size and shape; can detect chromosomal abnormalities • Monosomy: a zygote with only 45 chromosomes; one copy of a chromosome • Trisomy: three copies of a chromosome; 47 chromosomes total • Both result from nondisjunction

21. Down's Syndrome • Trisomy 21 • Mild to severe mental retardation • Distinct Facial Features • Heart Defects • Fingerprints – Sworl • Most Common Birth Defect – 1/700 births • Mother’s Age over 40 – 1/80 • Problems during Oogenesis

22. Klinefelter's Syndrome • Trisomy of sex chromosomes; XXy male • Feminine Characteristics, Infertile • George Washington? • No Children – Sterile? • Dental Problems • Height – Very tall for generation • Still Inconclusive

23. Turner's Syndrome • Monosomy of Sex Chromosomes; XO female • Infertile • Dwarfism • Overweight • Some mental retardation • Webbed Neck

24. Edward's Syndrome • Trisomy 18 • Elfin Appearance • Low set ears • Malformation of many organs – specifically heart/lungs • “Blue Babies” due to lack of oxygen • 90% die within first 6 months

25. Edward's Syndrome

26. Patau's Syndrome • Trisomy 13 • Cleft Lip and Palate • Polydactyl – more than ten fingers/toes • 1/6000 births • Most die within first year

27. Cri-du-chat • “Cat’s Cry” Syndrome • Deletion of a portion of Chromosome 5 • Mental Retardation

28. Reproductive Technology • Invitrofertilization (IVF):“test tube babies” • Procedure: • Woman treated with fertility drugs to regulate menstrual cycle and develop high quality eggs • Eggs collected using a needle • Fertilization occurs in a Petri dish • Within 72 hours embryos transferred to uterus • Multiple births often occur • Artificial Insemination: fertilization occurs within uterus (in vivo) • Sperm inserted through a catheter passing through the cervix into the uterus

29. Ultra Sound • High frequency sound waves with computer produce image • Locate fetus during amniocentesis and CVS • Estimate fetal age, sex, twins • 600 disorders can be diagnosed prenatally • Spina bifida, heart defects, dwarfism, hydrocephalus (water on brain)

30. Ultra Sound

31. 3D Ultra Sound

32. Fetal Cells • Fetal Cells obtained from either amniocentesis or chorionic villi sampling (CVS) • Cultured and a karyotype created to diagnose genetic disorders • Alphafetoproteins (AFP) levels indicated in sample; different levels signal defects • Low AFP levels • Down’s Syndrome • High AFP levels • Spina Bifida: spinal cord not contained within spinal column • Twins

33. Genetic Screening • Genetic Screening: a person with family history for genetic disorders are screened before deciding to have children • Karyotype of individual created to check for any chromosomal abnormalities • Genetic Counseling:couples at risk for having children with genetic disorder seek medical guidance to determine their chances of having a child with a disorder • Punnett Squares

34. Amniocentesis • Needle removes small amount of amniotic fluid from sac surrounding baby • 14th – 16th week • Fetal cells and proteins are analyzed • Karyotype

35. PGD Preimplantation Genetic Diagnosis