It has been estimated that approximately 10% of the genome has been affected by linkage due to recent selective sweeps [5]. However, it is challenging to make direct and clear inference on the phenotypic that is the target of natural selection. This is particularly true when the phenotype being examined has no obvious evolutionary consequences, and has a disease or trait-related association with no clear reproductive consequence today, but where patterns of genetic variation are consistent with a positive selective sweep in recent human history. In this case, additional mechanisms and/or alternative explanations must be sought for the existence of selection on the gene of interest. An example of such a situation occurs in the gene encoding hemoglobin. In homozygous form, the ‘sickle cell’ allele, HbS, drives the formation of malformed red cells, which aggregate, blocking blood flow to numerous organs including the brain. This results in organ damage and strokes, severely shortening the lifespan of the individual. Nonetheless, the HbS allele is maintained in the gene pool in regions where malaria is endemic because in heterozygous form it provides
