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Lecture 10

Lecture 10 - Mapping and Genome Sequencing

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Biology 2581B
Jim Karagiannis

LECTURE 9: MAPPING AND GENOME SEQUENCING Key Concepts 1. Positional cloning 2. Chromosome mapping 3. Chromosome walking and jumping 4. Genome sequencing Positional Cloning • Finding a gene sequence based on its phenotype • Can be done with and without mapping information • HaemophiliaA: no mapping information • Cystic fibrosis: mapping information was needed Hemophilia and Colorblindness • Pedigrees indicate that colorblindness and two forms of hemophilia are X-linked traits • (a) Transmission of red-green colorblindness and hemophilia A. The traits travel together through the pedigree, indicating their genetic linkage. • (b) Transmission of red-green colorblindness and hemophilia B. Even though both genes are X linked, the mutant alleles are inherited together in only one of four grandsons in generation III. These two pedigrees indicate that the gene for colorblindness is close to the hemophiliaAgene but far away from the hemophilia B gene. HemophiliaA • “Old” interest – famous historical example • “New” interest: o Haemophilia patients received untested and unscreened clotting factor prior to 1992 o Extreme risk for contracting HIV and hepatitis C o Estimated that more than 50% of the haemophilia population contracted HIV from the tainted blood supply in the United States alone Positional Cloning • Finding the chromosomal location of a gene based on its phenotype • Example: finding a gene causing hemophiliaA HemophiliaA • One can clone a gene without mapping information if one has family history (X-linked, recessive, single gene) • Or an idea of what is causing the mutation o Aclotting factor o Mutation that inactivates this factor causes hemophiliaA • HemophilaAcloning o Protein sequencing o Often only a small protein is identified • Blood clotting cascade o Done by computer o Remember – not all amino acids are encoded by a single codon (wobble position) o Degenerate: a mixture of similar, but not identical sequences HemophiliaACloning • To confirm that they had the correct gene, gene
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