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Division Ave. High School Ms. Foglia AP Biology Human Genetic Diseases 1 AP Biology 3 2 4 5 2006-2007 6 Pedigree analysis n Pedigree analysis reveals Mendelian patterns in human inheritance u data mapped on a family tree = male = female = male w/ trait = female w/ trait AP Biology Simple pedigree analysis 11 33 44 What’s the likely inheritance pattern? 22 55 66 AP Biology 1 Division Ave. High School Ms. Foglia AP Biology Genetic counseling n Pedigree can help us understand the past & predict the future n Thousands of genetic disorders are inherited as simple recessive traits u from benign conditions to deadly diseases albinism cystic fibrosis n Tay sachs n sickle cell anemia n PKU n n AP Biology Genetic testing sequence individual genes AP Biology Recessive diseases n The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all u Heterozygotes (Aa) n n carriers have a normal phenotype because one “normal” allele produces enough of the required protein AP Biology 2 Division Ave. High School Ms. Foglia AP Biology Heterozygote crosses n Heterozygotes as carriers of recessive alleles Aa x Aa A Aa male / sperm female / eggs A AA AA A Aa Aa carrier Aa Aa a a a carrier A Aa aa a disease AP Biology Cystic fibrosis (recessive) n Primarily whites of European descent u strikes 1 in 2500 births n u n n n u AP Biology 1 in 25 whites is a carrier (Aa) normal lung tissue normal allele codes for a membrane protein that transports Cl- across cell membrane defective or absent channels limit transport of Cl- & H 2O across cell membrane thicker & stickier mucus coats around cells mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections without treatment children die before 5; with treatment can live past their late 20s Chloride channel Effect on Lungs normal lungs airway Cl– transports salt through protein channel out of cell Osmosis: H 2O follows Cl– Cl– channel H 2O cells lining lungs cystic fibrosis Cl– H 2O bacteria & mucus build up thickened mucus hard to secrete AP Biology mucus secreting glands 3 Division Ave. High School Ms. Foglia AP Biology delta F508 loss of one amino acid AP Biology Tay-Sachs (recessive) n Primarily Jews of eastern European (Ashkenazi) descent & Cajuns (Louisiana) u strikes 1 in 3600 births n u non-functional enzyme fails to breakdown lipids in brain cells n fats collect in cells destroying their function n symptoms begin few months after birth seizures, blindness & degeneration of muscle & mental performance child usually dies before 5yo n AP Biology 100 times greater than incidence among non-Jews n Sickle cell anemia (recessive) n Primarily Africans u strikes 1 out of 400 African Americans n high frequency caused by substitution of a single amino acid in hemoglobin u when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods u deforms red blood cells into sickle shape n sickling creates pleiotropic effects = cascade of other symptoms n AP Biology 4 Division Ave. High School Ms. Foglia AP Biology Sickle cell anemia n Substitution of one amino acid in polypeptide chain hydrophilic amino acid AP Biology hydrophobic amino acid AP Biology Sickle cell phenotype n 2 alleles are codominant both normal & mutant hemoglobins are synthesized in heterozygote (Aa) u 50% cells sickle; 50% cells normal u carriers usually healthy u sickle-cell disease triggered under blood oxygen stress u n exercise AP Biology 5 Division Ave. High School Ms. Foglia AP Biology Heterozygote advantage n Malaria single-celled eukaryote parasite spends part of its life cycle in red blood cells n In tropical Africa, where malaria is common: u homozygous dominant individuals die of malaria u homozygous recessive individuals die of sickle cell anemia u heterozygote carriers are relatively free of both u n reproductive advantage n High frequency of sickle cell allele in African Americans is vestige of African roots AP Biology Prevalence of Malaria Prevalence of Sickle Cell Anemia AP Biology Huntington’s chorea (dominant) n Dominant inheritance u Testing… Would you want to know? u AP Biology 1872 repeated mutation on end of chromosome 4 n mutation = CAG repeats n glutamine amino acid repeats in protein n one of 1 st genes to be identified build up of “huntingtin” protein in brain causing cell death n memory loss n muscle tremors, jerky movements w “chorea” n starts at age 30-50 n early death w 10-20 years after start 6 Division Ave. High School Ms. Foglia AP Biology Genetics & culture n Why do all cultures have a taboo against incest? laws or cultural taboos forbidding marriages between close relatives are fairly universal n Fairly unlikely that 2 unrelated carriers of same rare harmful recessive allele will meet & mate u but matings between close relatives increase risk n “consanguineous” (same blood) matings u individuals who share a recent common ancestor are more likely to carry same recessive alleles u AP Biology A hidden disease reveals itself Aa AA x Aa A AA AA a Aa Aa AP Biology female / eggs female / eggs A Aa male / sperm male / sperm A x A a A AA Aa a Aa aa • increase carriers in population • hidden disease is revealed Any questions? AP Biology 2006-2007 7 Division Ave. High School Ms. Foglia AP Biology Ghosts of Lectures Past (storage) AP Biology 2006-2007 Heterozygote advantage n Sickle cell frequency u high frequency of heterozygotes is unusual for allele with severe detrimental effects in homozygotes n n 1 out of 400 African Americans Suggests some selective advantage of being heterozygous u sickle cell: resistance to malaria? u cystic fibrosis: resistance to cholera? AP Biology Malaria AP Biology 8 Division Ave. High School Ms. Foglia AP Biology Woody Guthrie & Arlo Guthrie AP Biology 9