- The set of alleles that determine different antigens but are closely linked on one chromosome and inherited as a unit, providing a distinctive genetic pattern used in histocompatibility testing.
- The antigenic phenotype determined by closely linked genes inherited as a unit from one parent.
A haplotype, contraction of the phrase "haploid genotype", is the genetic constitution of an individual chromosome. In the case of diploid organisms such as humans, the haplotype will contain one member of the pair of alleles for each site. A haplotype can refer to only one locus or to an entire genome. A genome-wide haplotype would comprise half of a diploid genome, including one allele from each allelic gene pair.
In a second meaning it refers to a set of single nucleotide polymorphisms (SNPs) found to be statistically associated on a single chromatid. With this knowledge, the identification of a few alleles of a haplotype block unambiguously identifies all other polymorphic sites in this region. Such information is most valuable to investigate the genetics behind common diseases and is collected by the International HapMap Project.
In relation to genotypes
A genotype is distinct from a haplotype because an individual's genotype may not uniquely define that individual's haplotype.
As an example, consider two loci, each with two possible alleles, the first locus being either A or a, the second locus being B or b. If the genotype of an individual was found to be AaBb, there are two possible sets of haplotypes, corresponding to which pairs happen to occur on the same chromosome:
|haplotype at chromosome 1||haplotype at chromosome 2|
|haplotype set 1||AB ||ab|
|haplotype set 2||Ab ||aB|
In this case, more information would be required to determine which particular set of haplotypes occur in the individual (i.e. which alleles appear on the same chromosome).
Given the genotypes for a number of individuals, the haplotypes can be inferred by haplotype resolution or haplotype phasing techniques. These methods work by applying the observation that certain haplotypes are common in certain genomic regions. Therefore given a set of possible haplotype resolutions, these methods choose those which use fewer different haplotypes overall. The specifics of this method vary - some are based on parsimony, while others use likelihood functions in combinations with algorithms such as expectation-maximization algorithm (EM) or Markov chain Monte Carlo (MCMC).
In genealogical DNA testing
A Y chromosome haplotype is the numbered results of a Y-DNA genealogical DNA test. Within genealogical and popular discussion this is sometimes referred to as the "DNA signature" of a particular male human, or of his paternal bloodline with whom he should largely share the same Y chromosome give or take a few mutations.
When testing various descendants with the same surname, a modal haplotype can sometimes be determined for the surname. This is the most likely haplotype of the oldest common ancestor with that surname.
Unlike many other haplotypes, those of Y chromosomes do not come in pairs. Every human male has one copy only of that chromosome.
Haplotypes may be used to compare different populations. Haplotype diversity refers to the uniqueness of a particular haplotype in a given population. Haplogroups are large groups of haplotypes that can be used to define genetic populations and are often geographically oriented.
Origins of the haplotypes
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.
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. Source
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.