Triplet Expansion Diseases Modes of Gene<c Inheritance Sex Linkage Color Blindness Discuss Katherine Moser, WSJ aracle, on facing HunAngton Disease.
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1 9/8/17 Week 3 Genetic Disease Detection Reviewing Gene Expression Triplet Expansion Diseases Modes of Gene<c Inheritance ex Linkage Color Blindness Discuss Katherine Moser, WJ aracle, on facing HunAngton Disease. BIO10191 Biology s Impact in Our World Dominant vs. Recessive Mutant Versions of Gene Affects a Protein Mendel s peas x = makes an active protein that performs role in plant cells that makes the pea seed smooth. = a mutant form of the protein that is defective and unable to make the pea seed become smooth. -GLY-AP-LEU-ER- In a heterozgote ( / ), why is the pea smooth? Can you imagine a different result? x (video 2:35) Why are some mutations dominant and some mutations recessive? -GLY-AP-VAL-ER- C/C Risk associated with inheritance of Hun<ngton Disease? Q1. Is the man identified in generation 3 (arrow) at risk? c/c Q2. What is the probability that he will develop Huntington s Disease? 1
2 9/8/17 Risk associated with inheritance of Hun<ngton Disease Q3. Is the man identified in generation 3 (arrow) at risk? Q4. What is the probability that he will develop Huntington s Disease? HTT 1st exon has expanded CAG segment Detecting a Genetic Disease 1. First step is identifying the molecular basis of the disease. The HD gene is on 4th chromosome spans 180 kb and consists of 67 exons ranging in size from 48 bp to 341 bp with an average of 138 bp. What did we learn about the cause of Huntington Disease? HD gene Mature RNA produced equencing DNA (1) Obtain DNA from an individual, (2) run Polymerase Chain Reac<on, (3) sequence amplified DNA. 1. What is expected effect on Huntingtin protein? 2. How would you design a genetic test to identify the Huntington disease gene? equencing DNA à tart Wednesday equencing DNA 2
3 9/8/17 Week 3 Wednesday BIO10191 Biology s Impact in Our World Genetic Disease Detection Today: 1. ome more background on Friday s lab. 2. tudent talks on the set of Genetic Diseases. 3. ex-linked genes (chromosome) 4. Frequency of disease genes within the population Friday Lab Restriction Enzymes- a bacterial defense system How do restric<on enzymes work?..atcgcgattacggaattcaatgcatttagcgcgatatagcttaaaccgttaagg....tagcgctaatgccttaagttacgtaaatcgcgctatatcgaatttggcaattgg.. The enzyme recognizes a palindrome in the DNA and EcoR1 restric<on enzyme site: 5...GAATTC CTTAAG... Cuts the DNA at this site: AATTCAATGCATTTAGCGCGATATAGCTTAAACCGTTAAGG....ATCGCGATTACGG GTTACGTAAATCGCGCTATATCGAATTTGGCAATTGG....TAGCGCTAATGCCTTAA T (Taster version of gene (T allele) t (non-taster version of gene (t allele) GGCC GGCC GGGC Friday Lab Results? tudent #1 tudent #2 tudent #3 Uncut Cut Uncut Cut Uncut Cut ize tandard GCCC HaeIII Restric<on enzyme site: 5...GGCC CCGG... HaeIII 5...GG 3...CC CC... GG... ex Linkage tudent Presenta<ons -medical condi<on -mode of inheritance -nature of gene product coded by the defec<ve gene -impact on afflicted individuals and their families Note: this slide is as far as we got on Wednesday. We will finish topic and rest of slides posted here on Monday before starang next topic on AnAbioAcs/ImmunizaAons. I will remove some content from next week s lectures to get us back on the syllabus schedule. Males don t really have 23 pairs of chromosomes, Rather 22 pairs and both an and Y ( Y) chromosome. Females do have 23 pairs, the same 22 pairs as in the male and a pair ( ) of chromosomes. 3
4 9/8/17 ex Determination Father Produces Gametes: Y Y Y Y Mother Produces Gametes: Y Y Other Modes of Genetic Inheritance ex Linkage: Red-Green Color Blindness chance of being colorblind Men Women 1/20 1/400 Hardy-Weinberg Distribu<on Y Y Hardy-Weinberg Distribu<on q=frequency of allele p=frequency of allele If a popula<on is made up of AA, Aa, aa individuals and: frequency of A allele (p) = 50% frequency of a allele (q) = 50% What % of popula8on will be AA, Aa and aa? 4
5 9/8/17 ickle Cell Anemia In the United tates, a majority of pa<ents es<mates are 60-80% are African-American. People of Indian, Middle Eastern, Hispanic and Mediterranean heritage are also commonly affected. ickle Cell Disease HHMI Video on ickle Cell - 15 minutes HbA/HbA no anemia sensi<ve to malaria HbA/Hb slight anemia resistant to malaria Hb/Hb severe sickle cell highly resistant anemia to malaria àis there a most favorable genotype? Common gene<c diseases, due to heterozygote advantage? Africans: ickle Cell Anemia Heterozygote have resistance to malaria Caucasians: Cys8c Fibrosis Heterozygote resistance to cholera, tuberculosis? PKU=phenylketonuria 5
6 9/8/17 PKU pa<ents lack a func<onal enzyme known as phenylalanine hydroxylase. In persons with PKU, dietary phenylalanine accumulates in the body. Phenylalanine accumula<on disrupts brain development, leading to severe mental disabili<es. Q1. Do you expect the gene<c disease to be recessive or dominant? Q2. How could you prevent individuals with PKU from developing the mental disabili<es caused by accumula<on of phenylalanine? Wrapping Up àjordan lab on Friday then ed Week 4A for Monday: Antibiotics and Immunizations Our objec<ves today: Prep for Friday lab tudent presenta<ons, describe a gene<c disease Calcula<ng gene frequencies (Hardy-Weinberg) Insights from sickle cell disease Heterozygous overdominance Environmental influence on gene<c fitness 6
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