Editing Haplotype (section)

==Haplotype resolution==

An organism's [[genotype]] may not define its haplotype uniquely.  For example, consider a [[diploid]] organism and two bi-allelic [[locus (genetics)|loci]] (such as [[single-nucleotide polymorphism|SNPs]]) on the same chromosome.  Assume the first locus has alleles ''A'' or ''T'' and the second locus ''G'' or ''C''. Both loci, then, have three possible [[genotypes]]: (''AA'', ''AT'', and ''TT'') and (''GG'', ''GC'', and ''CC''), respectively.  For a given individual, there are nine possible configurations (haplotypes) at these two loci (shown in the [[Punnett square]] below).  For individuals who are homozygous at one or both loci, the haplotypes are unambiguous - meaning that there is not any differentiation of haplotype T1T2 vs haplotype T2T1; where T1 and T2 are labeled to show that they are the same locus, but labeled as such to show it does not matter which order you consider them in, the end result is two T loci. For individuals [[heterozygous]] at both loci, the [[gametic phase]] is [[ambiguous]] - in these cases, an observer does not know which haplotype the individual has, e.g., TA vs AT.

{| class="wikitable"
|-
! {{diagonal split header|Locus 2|Locus 1}}
! AA
! AT
! TT
|-
! GG
| AG AG
| AG TG
| TG TG
|-
! GC
| AG AC
| AG TC<br>or<br>AC TG
| TG TC
|-
! CC
| AC AC
| AC TC
| TC TC
|}

The only unequivocal method of resolving phase ambiguity is by [[DNA sequencing|sequencing]].  However, it is possible to estimate the probability of a particular haplotype when phase is ambiguous using a sample of individuals.

Given the genotypes for a number of individuals, the haplotypes can be inferred by haplotype resolution or [[Haplotype estimation|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 that use fewer different haplotypes overall. The specifics of these methods vary - some are based on combinatorial approaches (e.g., [[Occam's razor|parsimony]]), whereas others use likelihood functions based on different models and assumptions such as the [[Hardy–Weinberg principle]], the [[coalescent theory]] model, or perfect phylogeny. The parameters in these models are then estimated using algorithms such as the [[expectation-maximization algorithm]] (EM), [[Markov chain Monte Carlo]] (MCMC), or [[hidden Markov model]]s (HMM).

[[Microfluidic whole genome haplotyping]] is a technique for the physical separation of individual chromosomes from a [[metaphase]] cell followed by direct resolution of the haplotype for each allele.

===Gametic phase===
In [[genetics]], a '''gametic phase''' represents the original allelic combinations that a [[diploid]] individual inherits from both parents.<ref name = buckleton2018>{{cite book | last1 = Taylor | first1 = Duncan | last2 = Bright | first2 = Jo-Anne | last3 = Buckleton | first3 = John S. | title = Forensic DNA Evidence Interpretation | chapter = Biological basis for DNA evidence | editor-last1 = Buckleton | editor-first1 = John S. | editor-last2 = Bright | editor-first2 = Jo-Anne | editor-last3 = Taylor | editor-first3 = Duncan | publisher = CRC Press | edition = 2nd | date = 2016 | location = Boca Rotan, FL | pages = 1–36 | isbn = 9781482258899}}</ref> It is therefore a particular association of [[alleles]] at different loci on the same [[chromosome]].  Gametic phase is influenced by [[Genetic linkage#Recombination frequency|genetic linkage]].<ref>{{cite journal|last=Excoffier|first=Laurent|title=Gametic phase estimation over large genomic regions using an adaptive window approach|journal=Human Genomics|date=1 November 2003|volume=1|issue=1|doi=10.1186/1479-7364-1-1-7|pages=7–19|pmc=3525008|pmid=15601529 |doi-access=free }}</ref>