chapter  23
32 Pages


WithGlenys Thomson, Ana Maria Valdes

The complete sequencing of the 3000 million bases (Mb) of the human genome has had a tremendous impact on the research community’s ability to discover the genes that underlie human genetic variation (1,2). Recent successes in the genetic mapping of Mendelian traits and diseases have been remarkable. However, progress has been exceedingly slow in elucidating the genetic components of complex diseases and traits, such as cardiovascular diseases, asthma, diabetes, rheumatoid arthritis, obesity, alcoholism, and schizophrenia. Genetic variation is likely to contribute to the risk of many complex diseases; in some cases the genetic component may be small compared to environmental factors. The fact that genes and environment interact only adds to the challenge of unraveling the etiology of these disorders. Rather than being due to specific and relatively rare mutations, complex diseases and traits may result principally from genetic variation that is relatively common in the general population. Examples include apolipoprotein E gene (APOE) variation and age of onset of Alzheimer’s disease, the angiotension-converting enzyme gene (ACE) and myocardial infarction, the chemokine receptor CCR5 gene (CMKBR5) and the risk of infection in those exposed to HIV, and the many diseases for which immune response genes of the HLA region have been implicated.