The haplotypes in the human genome have been produced by the molecular mechanisms of sexual reproduction and by the history of our species.

With the exception of the sex cells, the chromosomes in human cells occur in pairs. One member of each chromosome pair is inherited from a person's father; the other member of the pair is inherited from that person's mother. But chromosomes do not pass from each generation to the next as identical copies. Rather, when sperm and egg cells are being formed, the chromosome pairs undergo a process known as recombination. The members of each chromosome pair come together and exchange pieces. The result is a hybrid chromosome containing pieces from both members of a chromosome pair, and this hybrid chromosome is passed on to the next generation.

Figure 1: This diagram shows two ancestral chromosomes being scrambled through recombination over many generations to yield different descendant chromosomes. If a genetic variant marked by the A on the ancestral chromosome increases the risk of a particular disease, the two individuals in the current generation who inherit that part of the ancestral chromosome will be at increased risk. Adjacent to the variant marked by the A are many SNPs that can be used to identify the location of the variant.

Over the course of many generations, segments of the ancestral chromosomes in an interbreeding population are shuffled through repeated recombination events. Some of the segments of the ancestral chromosomes occur as regions of DNA sequences that are shared by multiple individuals (Figure 1). These segments are regions of chromosomes that have not been broken up by recombination, and they are separated by places where recombination has occurred. These segments are the haplotypes that enable geneticists to search for genes involved in diseases and other medically important traits.

The fossil record and genetic evidence indicate that all humans today are descended from anatomically modern ancestors who lived in Africa about 150,000 years ago. Because we are a relatively young species, most of the variation in any current human population comes from the variation present in the ancestral human population. Also, as humans migrated out of Africa, they carried with them part but not all of the genetic variation that existed in the ancestral population. As a result, the haplotypes seen outside Africa tend to be subsets of the haplotypes inside Africa. In addition, haplotypes in non-African populations tend to be longer than in African populations, because populations in Africa have been larger through much of our history and recombination has had more time there to break up haplotypes.

As modern humans spread throughout the world, the frequency of haplotypes came to vary from region to region through random chance, natural selection, and other genetic mechanisms. As a result, a given haplotype can occur at different frequencies in different populations, especially when those populations are widely separated and unlikely to exchange much DNA through mating. Also, new changes in DNA sequences, known as mutations, have created new haplotypes, and most of the recently arising haplotypes have not had enough time to spread widely beyond the population and geographic region in which they originated.