1. Chapter 6 PART II: Concepts in Molecular Biology and Genetics The Human Genome: Implications for the Understanding of Human Disease Companion site for Molecular Pathology Author: William B. Coleman and Gregory J. Tsongalis

2. Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved. 2 Human Genome Project timeline. The vertical timeline emphasizes the major years of the Human Genome Project (HGP) boxed in green with a summary of what occurred in that year to the right of the date. FIGURE 6.1

3. Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved. 3 Positional gene cloning. The flow diagram highlights the steps that are used to determine the location of a disease-related gene without understanding its function. Linkage analysis is used to map the chromosomal location of the disease-causing gene. FIGURE 6.2

4. Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved. 4 Functional gene cloning. The flow diagram highlights the steps that are used to determine the location of a disease-related gene when the function of the protein product is known. Oligonucleotide probes are used to screen a selected gene sequence. FIGURE 6.3

5. Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved. 5 Positional candidate gene cloning. The flow diagram highlights the steps that are used to determine the location of a disease-related gene when the chromosomal location is known and that location is used to identify good candidates for testing. FIGURE 6.4

6. Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved. 6 DNA rearrangements. Structural variations in the human genome result from rearrangements of DNA from gross changes to single nucleotide alterations. The letters are used to depict nucleotides in a DNA sequence and lines are used to depict a gene. Each DNA rearrangement is outlined by a red box. The red arrow represents a nucleotide deletion. FIGURE 6.5