Genetic Disorders

1. Genetic Disorders • Inherited in different ways • Gene mutations • Autosomal / Sex-linked • Dominant / recessive/ codominant • Chromosomal mutations • Too many- trisomy • Too few- monosomy • Deletions of large portions of the chromosome

2. Tay Sachs • Autosomal Recessive • Lack of enzyme hexosaminidase A (hex A), which breaks down fatty acids in brain in nervous tissue • Symptoms begin to appear at 4-6 months • Developmental delay, loss of motor skills and mental functions, blindness, deafness, paralysis, non-responsive to the environment • Death by 5 years • Found primarily in those descendants of Ashkenazi Jews • 1/30 American Jews carry the gene

3. Cystic Fibrosis • Autosomal recessive- • Chromosome #7 - 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 • Northern European descent

4. Albinism • Autosomal recessive • On one of many genes controlling pigment production • Lack of pigment in the skin, hair, and eyes

5. Phenylketonuria (PKU) • Autosomal recessive- Chromosome #12 • 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) • Learning Difficulties, seizures • 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%

6. Achondroplasia • Autosomal dominant • 1 of 6 kinds of Dwarfism (each has different characteristics • Normal torso length with shortened limbs • Most common form of dwarfism • Homozygous dominant zygotes will miscarry

7. Huntington's Disorder • Autosomal Dominant- chromosome #4 • Lethal due to degeneration of brain cells • Symptoms onset around ages 35-50 • Lose control over muscles causing uncontrolled movements, loss of intellectual faculties, and emotional disturbance

8. Familial high cholesterol Autosomal codominant on Chromosome #19 Cells have reduced ability to remove cholesterol (lipids) from the blood which causes a build up in the arteries (called atherosclerois) Blockage leads to early age heart attacks Hypercholesterolemia

9. Hypercholesterolemia • Treated with medicines like Lipator, Mevacor, Zocor

10. Sickle Cell Anemia • Autosomal Codominant • Defective Hemoglobin on RBCs caused by 1 nucleotide base deletion  shape change • Damage to brain, heart, lungs • Carriers are protected from malaria • African descent; 1/10 African Americans in US is a carrier

11. 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

12. Holandric Traits • Holandric Traits: genes on the y chromosome; carry genes for male sexual characteristics • Absence of these genes causes female development • Small arm of y chromosome responsible for individuals that have a sex chromosome combination that does not match their appearance • XX males and XY females due to absence or presence of SRY factor • Ghengis Khan • Mongolian warrior 13th century • 8% of men living in region that was once Mongolian empire have same y chromosome

13. Hemophilia • sex-linked recessive • On 1 of 2 genes producing clotting factor located on the X chromosome • Most Common in males • “Bleeder’s Disease” • Bleeding spontaneously and in joints • Queen Victoria: descendents affected with hemophilia Alexei Romanov

14. Duchenne Muscular Dystrophy • sex-linked recessive • Most Common in males • 1/3500 • Progressive muscle weakening and enlargement • Dystrophin • Protein that provides support for the cell; without it, cell enlarges and explodes

15. Colorblindness • sex-linked recessive • On 1 of 3 color vision genes on the X chromosome • Cannot distinguish between different colors • Most common type is red/green colorblindness • Heterozygous female is considered a carrier • Heterozygous females have mosaic retinas in which they have patches of color vision

16. Down Syndrome • Chromosomal (Autosomal) • Trisomy 21 • Mild to severe learning disabilities, Distinct Facial Features, Heart Defects, low muscle tone • Most Common Birth Defect – 1/700 births • Mother’s Age 30 – 1 in 1000 • Mother’s Age over 45 – 1 in 25 • Can live until 50s

17. Klinefelter Syndrome • Chromosomal (Sex chromosomes) • Trisomy XXY male • 1 per 1,000 males (most do not know they have an extra X chromosome) • Feminine Characteristics, Sparse facial and body hair, dental problems, tall • Infertile (cannot produce sperm)

18. Turner Syndrome • Chromosomal (Sex Chromosome) • Monosomy XO female • Infertile, Short stature, • Overweight, Some learning difficulties, Webbed Neck, no menstruation • 1 out of 2,000 live births. • 96-98% do not survive to birth

19. Edward Syndrome • Chromsomal (Autosomal) • Trisomy 18 • Elfin Appearance, Low set ears, Clenched hands, Heart disease, Kidney problems, Low birth weight, Small head, Small jaw (micrognathia) • 1 out of 3,000 live births • 90% die within first 6 months

20. Patau's Syndrome • Chromsomal (Autosomal) • Trisomy 13 • Cleft Lip and Palate, Polydactyly, Cleft lip or palate, Close-set eyes (eyes may actually fuse together into one), Low-set ears, Severe learning difficulties, Seizures. Small eyes, Small head • 1 in 10,000 births • 80% die within first month

21. Cri-du-chat • “Cat’s Cry” Syndrome • Deletion of a portion of Chromosome 5 • Developmental delay, Moon-shaped face, Heart disease, Malformed larynx • 1 in 216,000 births • Normal lifespan

22. Aniridia-Wilms Tumor Syndrome #11 Deletion of upper arm Developmental delay, Blindness, Tumors on kidneys 1 in 50,000,000 births Short lifespan

23. Thirteen Q Deletion Syndrome • #13 Deletion of lower arm • Developmental Delay, Malformed face, No thumbs, Heart disease • 1 in 500,000 births • Short lifespan

24. Triple X Syndrome Tall stature, Mild facial characteristics (increased width between eyes and proportionately smaller head size), learning disabilities, speech and language delays, poor coordination, introverted, normal sexual development 1 in 2,500 births Normal lifespan

25. XYY Syndrome XYY only; #23 Trisomy Highly variable: sometimes taller than average, increased risk of learning disabilities, delayed speech and language skills, behavioral problems, normal sexual development 1 in 1,000 males

26. Genomic Imprinting • Genomic Imprinting: variation in phenotype expression depending on which parent gave the chromosome • Chromosome “remembers” which parent it came from • EX: Deletion of Chromosome 15 • Prader-Willi: uncontrollable eating, diabetes, mental retardation • Deletion of portion of paternal 15 • Angleman’s: behavior problems, some mental retardation • Deletion of portion of maternal 15