nadians have one of the highest prevalences of this disease in the world because of the small founding populations followed by population expansion (Moorjani et al., 1989).
There are also a number of examples where mutations that arise in an individual become more prevalent because of the selective advantage they impart on their carriers. The best known example is the mutation associated with sickle cell anemia. The geographical pattern of this mutation strongly mirrors the geographical pattern of malarial infection. It has been molecularly demonstrated that individuals carrying the sickle cell mutation have a resistance to malarial infection. Because many of the selection pressures that may have given rise to the current distribution of mutations in particular populations are in our evolutionary past, it is difficult to assess how much variation within or among populations is due to these types of selection forces.
Another major force in determining the distribution of genetic variations within and among human populations is their migration and reproductive isolation. According to our best knowledge, one of the most important periods in human evolution occurred approximately 100,000 years ago, when some humans migrated to other continents from the African basin and established new communities with relative reproductive isolation. Genetic differences among people in different geographical areas have been associated with the concept of race for hundreds of years. Although race is still used as a label, the original concept of race as genetically distinct subspecies of humans has been rejected through modern genetic information. For numerous reasons, discussed in the section below, it is more appropriate to reconceptualize the old genetics of race into a more accurate genetics of ancestry.
In addition to distant evolutionary patterns of migration, more modern migration patterns also have had a profound effect on the genetics of populations. For example, the current population of the United States and much of North America is very diverse genetically as a consequence of the mixing of many people from many different countries and continents.
A central reason for studying the origins and nature of human genetic variation is that the similarities and differences in the type and frequencies of genetic variations within and among populations can have a profound impact on studies that attempt to understand the influence of genes on disease risk. For example, some genetic variations, such as the apolipoprotein E protein polymorphisms, are found in every population and have very similar genotype frequencies around the world (Wu et al., 2002; Deniz Naranjo et al., 2004). The variation’s association with increased heart disease and Alzheimer’s disease could be and has been tested in many of the world’s populations. Other mutations such as the 10kb