Lecture 14 Chapter 13 - Introduction to Genetic Analysis...

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    1 Introduction to Genetic Analysis Ninth Edition Anthony J. F. Griffiths, Susan R. Wessler, Richard C.  Lewontin, and Sean B. Carroll CHAPTER 13 Genomes and Genomics Copyright 2008 © W H Freeman and Company
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    2 Before the Genome Project Genes were found through Candidate Gene Approach
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    3 Candidate Gene Approach Map disease to chromosome and then to a specific  chromosomal band
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    4 Candidate Gene Approach Localize disease further within the band in relation to markers
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    5 Candidate Gene Approach Cloning a contiguous DNA region using DNA probes of overlapping  clones
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    6 Candidate Gene Approach Refined localization of disease gene using microsatellite  markers Disease tracking  with M’’
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    7 Candidate Gene Approach Examine all the genes within the interval and pick out candidate gene  based on tissue of expression or other criteria.
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    8 Positional Cloning of the Cystic  Fibrosis (CF) Gene An autosomal recessive disorder Chronic bronchopulmonary  infection Bronchiectasis pancreatic insufficiency biliary cirrhosis  meconium ileus in neonates distal intestinal obstruction  syndrome male infertility  The disease was mapped by  linkage disequilibrium studies to  Chromosome 7q31 
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    9 Positional Cloning
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    10 There are four known genes in the  CF  gene  region
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    11 Northern Blot Analysis of  CF  Candidate  Genes Of the 4 candidate genes,  only one is expressed in the  pancreas and lungs, the  tissues affected by cystic  fibrosis.
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    12 The Cystic Fibrosis Gene Encodes   a Cell Membrane Protein that Regulates the Passage of  Chloride Through the Membrane
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    13 Candidate Gene Approach The candidate gene approach is cumbersome and slow. In order to have a significant impact on biomedicine gene  discovery had to be expedited. A concerted effort to clone and sequence the entire genome  was proposed as a solution in 1980s.
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    14
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    16 1. Generate Chromosome Maps 1. Sequence Entire Genome  1 error in 10 4  bases 1. Identify Full Set of Genes 1 error in 10 5  bases 1. Sequence Model Organisms 1. Develop Computational Tools for gene analysis and  data mining 1. 1. 1. Goals of the Human Genome Project
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    17 The Human Genome Project International Scientific Effort 5 major Institutes (G5) 16 total Institutes (G16) Funded by the U.S. and other Federal Governments.  In U.S.: 1990-2005 Dept. of Energy (DOE) National Institute of Health (NIH) National Human Genome research Institute (NHGRI)
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    18 The Human Genome Project: Who was involved in the public effort?
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Lecture 14 Chapter 13 - Introduction to Genetic Analysis...

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