Genomics, genetic epidemiology, and genomic medicine Konstantinos N. Lazaridis, Gloria M. Petersen  Clinical Gastroenterology and Hepatology  Volume 3, Issue 4, Pages 320-328 (April 2005) DOI: 10.1016/S1542-3565(05)00085-6 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 In Mendelian diseases, a single gene is responsible for causing a disorder, and the disease phenotype follows a predicted inheritance pattern (ie, autosomal dominant, autosomal recessive, or X-linked). In a family, all affected members carry exactly the same mutation. Mendelian diseases are characterized by a close correspondence of a genotype to a phenotype. Modified and reprinted with permission from Peltonen L, et al.5 Science 2001;291:1224–1229. Copyright 2001 AAAS (www.sciencemag.org). Clinical Gastroenterology and Hepatology 2005 3, 320-328DOI: (10.1016/S1542-3565(05)00085-6) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 In complex diseases, multiple genetic variants interact with each other along with the environment to cause the disease phenotype. Each genetic variant and the environment have a small effect on the phenotype. Because of the contribution of several genetic variants and environmental factors, complex diseases are heterogeneous in their pathogenesis, progression, and response to treatment. Modified and reprinted with permission from Peltonen L, et al.5 Science 2001;291:1224–1229. Copyright 2001 AAAS (www.sciencemag.org). Clinical Gastroenterology and Hepatology 2005 3, 320-328DOI: (10.1016/S1542-3565(05)00085-6) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 3 In complex diseases, the susceptibility genotype of 2 unrelated individuals (A and B) and their separate interactions with the environment define the present health status. The genotypes norm of reaction will determine the future health course (ie, healthy vs sick separated by the dotted line). Modified and reprinted with permission from Sing CF, et al.24 In: Variation in the human genome. Chichester, UK: John Wiley and Sons, 1996:211–232. Clinical Gastroenterology and Hepatology 2005 3, 320-328DOI: (10.1016/S1542-3565(05)00085-6) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 4 The position of a genetic variant (SNP) is shown with an arrow on an ancestral chromosome. Because of meiotic recombination that occurs over thousands of generations, contemporary chromosomes have variable length segments of the common ancestral chromosome (regions shown in white) that flank the original SNP (arrowhead), whereas new chromosomal sections introduced by recombination are depicted by regions shown in gray. Thus, genetic markers (SNPs) within the regions shown in white that are in physical proximity with the original SNP (arrowhead) will remain associated and in linkage disequilibrium to the latter. Modified and reprinted with permission from Ardlie KG, et al.25 (http://www.nature.com/). Clinical Gastroenterology and Hepatology 2005 3, 320-328DOI: (10.1016/S1542-3565(05)00085-6) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 5 Genomics will likely lead to better understanding of genetic variation as a susceptibility of disease. This knowledge will improve our diagnosis, treatment, and hopefully prevention of human illnesses. Clinical Gastroenterology and Hepatology 2005 3, 320-328DOI: (10.1016/S1542-3565(05)00085-6) Copyright © 2005 American Gastroenterological Association Terms and Conditions