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320-14&15 - Genetics part 2 from genotype to...

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Genetics, part 2: from genotype to phenotype office: Centers for Molecular Medicine, room 447 (just over the 4th floor bridge from Life Sciences) Hours: drop by any time, or email for an appointment: [email protected] Maurice Kernan Dept. of Neurobiology & Ctr. for Developmental Genetics my research: uses Drosophila genetics to study mechanosensory transduction - how sound and touch are converted to electrical signals in the nervous system.
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Why I do (and teach) genetics The unifying basis for biology: the universal “logic of life”. A powerful set of tools to engineer living systems. A way to discover molecules and mechanisms in biology. An analytical technique, a way of thinking - not just a set of facts… A new type of knowledge about ourselves… A new window on our past… A transforming force in medicine, law and politics.
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14-16 Basics of gene expression - getting from DNA to protein; - regulating gene expression (in bacteria) Genotype Phenotype Gene expression Gene transmission 17-19 Tools & techniques - recombinant DNA - DNA cloning & amplification - sequencing & genomics - analysing variant genotypes
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24-26 Change, variation & complexity - population genetics, human evolution - genetics of quantitative & complex traits - “heritability” in humans; behavioral genetics 20-23 Gene expression in eukaryotes: - chromosomes & expression: imprinting - cell cycle regulation and cancer genetics - gene expression and development.
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Proteins carry out most biochemical functions Genes control phenotype because they can encode proteins. DNA is inert - it has little biochemical activity Genotype 1 gene Phenotype 1 enzyme polypeptide
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C NH 2 X C O N H C C O OH O C C H N Z Y Protein structure C NH 2 COOH X C NH 2 COOH Y C NH 2 COOH Z
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The “sequence hypothesis”: all protein properties determined by 1 o amino-acid sequence Text fig. 7.23 Levels of polypeptide structure
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Genotype base sequence DNA base sequence RNA Phenotype amino acid sequence Protein Information flows from DNA to RNA to protein - the “Central Dogma” of molecular biology. How does it work? - a genetic code How did it get started?
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1. How geneticists & biochemists cracked the code - clues from protein sequences and bacterial genetics - identifying the RNA message - using synthetic messages to read the code “dictionary” 2. How cells read the code - a simplifying assumption: the “sequence hypothesis”
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Theoretically possible codes: CGATGTTACCGTAGCTGCTA… Punctuated? CGA , TGT , TAC , CGT , AGC , TGC , TA… Reading frame? CGATGTTACCGTAGCTGCTA… Overlapping?
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Fig. 7.25 Properties of the code: clues from proteins Many mutations change single amino acids in a polypeptide Any amino acid can be followed by any other in protein sequences. - normal and mutant hemoglobins
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Theoretically possible codes: CGATGTTACCGTAGCTGCTA… Punctuated?
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