Human Genetic Diseases. AP Biology
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1 Human Genetic Diseases
2 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
3 Simple pedigree analysis What s the likely inheritance pattern?
4 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 n albinism n cystic fibrosis n Tay sachs n sickle cell anemia n PKU
5 Genetic testing sequence individual genes
6 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 carriers n have a normal phenotype because one normal allele produces enough of the required protein
7 Heterozygote crosses n Heterozygotes as carriers of recessive alleles Aa x Aa male / sperm A a Aa A a female / eggs A a AA Aa carrier Aa carrier aa disease Aa A a
8 Cystic fibrosis (recessive) n Primarily whites of European descent u strikes 1 in 2500 births n 1 in 25 whites is a carrier (Aa) u normal allele codes for a membrane protein that transports Cl - across cell membrane n defective or absent channels limit transport of Cl - & H 2 O across cell membrane n thicker & stickier mucus coats around cells n mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections u without treatment children die before 5; with treatment can live past their late 20s normal lung tissue
9 normal lungs cystic fibrosis Effect on Lungs Cl H 2 O cells lining lungs airway Chloride channel transports salt through protein channel out of cell Osmosis: H 2 O follows Cl Cl channel Cl H 2 O bacteria & mucus build up thickened mucus hard to secrete mucus secreting glands
10 delta F508 loss of one amino acid
11 Tay-Sachs (recessive) n Primarily Jews of eastern European (Ashkenazi) descent & Cajuns (Louisiana) u strikes 1 in 3600 births n 100 times greater than incidence among non-jews 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 n seizures, blindness & degeneration of muscle & mental performance n child usually dies before 5yo
12 Sickle cell anemia (recessive) n Primarily Africans u strikes 1 out of 400 African Americans n high frequency u caused by substitution of a single amino acid in hemoglobin u when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods n deforms red blood cells into sickle shape n sickling creates pleiotropic effects = cascade of other symptoms
13 Sickle cell anemia n Substitution of one amino acid in polypeptide chain hydrophilic amino acid hydrophobic amino acid
14
15 Sickle cell phenotype n 2 alleles are codominant u 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 n exercise
16 Heterozygote advantage n Malaria u 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 n reproductive advantage n High frequency of sickle cell allele in African Americans is vestige of African roots
17 Prevalence of Malaria Prevalence of Sickle Cell Anemia
18 Huntington s chorea (dominant) Testing Would you want to know? n Dominant inheritance u 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 u build up of huntingtin protein in brain causing cell death n memory loss n muscle tremors, jerky movements w chorea n starts at age n early death w years after start 1872
19 Genetics & culture n Why do all cultures have a taboo against incest? u 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
20 A hidden disease reveals itself AA x Aa Aa x Aa male / sperm A A male / sperm A a female / eggs A a AA Aa AA Aa female / eggs A a AA Aa Aa aa increase carriers in population hidden disease is revealed
21 Any questions?
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