Lect9 - One gene One enzyme hypothesis In the next few...

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1 One gene One enzyme hypothesis In the next few lectures, the following questions will be Addressed:
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2 One gene One enzyme hypothesis In the next few lectures, the following questions will be Addressed: What is the structure of a gene? How does a gene function? How is information stored on the gene? What is the relationship between genotype and phenotype?
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3 Pathways Biologists and clinicians want to address the question of how altering a particular set of base pairs that make up the 3 billion base pairs in the human genome led to this phenotype.
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4 Alkaptonuria egenerative disease. Darkening of connective tissue, arthritis arkening of urine Garrod characterized the disorder- sing Mendels rules- Autosomal recessive. ffected individuals had normal parents and normal offspring. 908Garrod termed the defect- inborn error of metabolism omogentisic acid is secreted in urine of these patients. his is an aromatic compound and so Garrod suggested that it as an intermediate that was accumulating in mutant individuals nd was caused by lack of enzyme that splits aromatic rings of mino acids. 958La Du showed that accumulation of homogentistic acid s due to absence of enzyme in liver extracts 994Seidman mapped gene to chromosome 3 in human 000Enzyme principally expressed in liver and kidneys
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5 How does a gene generate a phenotype? The experiments of Beadle and Tatum in the 1940’s provided the first insight into gene function. They developed the one gene/one enzyme hypothesis This hypothesis has three tenets:
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6 Consequences of mutations Lets say we know the biochemical pathway. With this pathway, what are the consequences of a mutation in geneB? Would the final product be produced? Would intermediate2 be produced? Would intermediate1 be produced? What happens if we add intermediate1 to the media? What happens if we add intermediate2 to the media?
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7 Neurospora Beadle and Tatum analyzed biosynthetic mutations in the haploid fungus Neurospora. It had the advantage in that it could be grown on a defined growth medium.
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8 Arginine biosynthetic mutants Beadle and Tatum set out to identify genes involved in the biosynthetic pathway that led to the production of the amino acid arginine. Neurospora has approximately 15,000 genes and only 4-5 of these
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Lect9 - One gene One enzyme hypothesis In the next few...

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