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| {{technical|date=April 2013}}
| | Nice to be here there, I am Adrianne and I totally delve that name. Vermont has always been simple home and I find it irresistible every day living suitable here. Gardening is what I do every week. I am a people manager even so soon I'll be without any help. You can find my website here: http://circuspartypanama.com<br><br>Here is my webpage ... clash of clans hack cydia ([http://circuspartypanama.com http://circuspartypanama.com]) |
| {{genetic genealogy}}
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| A '''haplotype''' (from the {{lang-el|ἁπλοῦς}}, ''haploûs'', "onefold, single, simple") in [[genetics]] is a combination of [[allele]]s ([[DNA]] sequences) at adjacent locations ([[locus (genetics)|loci]]) on a [[chromosome]] that are inherited together. A haplotype may be one locus, several loci, or an entire chromosome depending on the number of [[Genetic recombination|recombination]] events that have occurred between a given set of loci, if any occurred.
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| A second meaning of the term haplotype is a set of [[single-nucleotide polymorphism]]s (SNPs) on a single chromosome of a chromosome pair that are [[Association (statistics)|associated statistically]]. It is thought that these associations, and the identification of a few alleles of a haplotype sequence, can unambiguously identify all other polymorphic sites in its region. Such information is very valuable for investigating the genetics of common [[diseases]], and has been investigated for the human species by the [[International HapMap Project]].<ref>{{cite journal|author=The International HapMap Consortium|title=The International HapMap Project|journal=Nature|year=2003|volume=426|pages=789–796|url=http://www.nature.com/nature/journal/v426/n6968/pdf/nature02168.pdf|doi=10.1038/nature02168|pmid=14685227|issue=6968}}</ref><ref>{{cite journal|author=The International HapMap Consortium|title=A haplotype map of the human genome|journal=Nature|year=2005|volume=437|pages=1299–1320|url=http://www.nature.com/nature/journal/v437/n7063/pdf/nature04226.pdf|doi=10.1038/nature04226|pmid=16255080|issue=7063|pmc=1880871}}</ref>
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| Many genetic testing companies use the term 'haplotype' to refer to an individual collection of [[short tandem repeat]] (STR) allele mutations within a genetic segment, while using the term '[[haplogroup]]' to refer to the SNP/[[unique-event polymorphism]] (UEP) mutations which represents the [[clade]] to which a collection of potential haplotypes belong (the term clade referring to a set of people sharing a common ancestor).<ref>[http://www.familytreedna.com/facts_genes.aspx Facts & Genes. Volume 7, Issue 3]</ref>
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| ==Haplotype resolution==
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| 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 doesn't 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, you don't know which haplotype you have, e.g., TA vs AT.
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| {| class="wikitable"
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| |-
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| !
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| ! AA
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| ! AT
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| ! TT
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| |-
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| ! GG
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| | AG AG
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| | AG TG
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| | TG TG
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| |-
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| ! GC
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| | AG AC
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| | AG TC<br>or<br>AC TG
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| | TG TC
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| |-
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| ! CC
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| | AC AC
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| | AC TC
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| | TC TC
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| |}
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| 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.
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| 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 that use fewer different haplotypes overall. The specifics of these methods vary - some are based on combinatorial approaches (e.g., [[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 models]] (HMM).
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| [[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.
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| ==Y-DNA haplotypes from genealogical DNA tests==
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| {{main|Genealogical DNA test}}
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| Unlike other chromosomes, Y chromosomes do not come in pairs. Every human male has only one copy of that chromosome. This means that there is not any chance variation of which copy is inherited, and also (for most of the chromosome) not any shuffling between copies by [[Genetic recombination|recombination]]; so, unlike [[autosomal DNA|autosomal]] haplotypes, there is effectively not any randomisation of the Y-chromosome haplotype between generations. A human male should largely share the same Y chromosome as his father, give or take a few mutations; thus Y chromosomes tend to pass largely intact from father to son,
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| with a small but accumulating number of mutations that can serve to differentiate male lineages.
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| In particular, the Y-DNA represented as the numbered results of a [[genealogical DNA test|Y-DNA genealogical DNA test]] should match, except for mutations.
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| ===UEP results (SNP results)===
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| [[Unique-event polymorphism]]s (UEPs) such as SNPs represent [[haplogroup]]s. STRs represent haplotypes. The results that comprise the full Y-DNA haplotype from the Y chromosome DNA test can be divided into two parts: the results for UEPs, sometimes loosely called the SNP results as most UEPs are [[single-nucleotide polymorphisms]], and the results for [[Microsatellite (genetics)|microsatellite]] [[short tandem repeat]] sequences ([[Y-STR]]s).
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| The UEP results represent the inheritance of events it is believed can be assumed to have happened only once in all human history. These can be used to identify the individual's [[Human Y-chromosome DNA haplogroups|Y-DNA haplogroup]], his place in the "family tree" of the whole of humanity. Different Y-DNA haplogroups identify genetic populations that are often distinctly associated with particular geographic regions; their appearance in more recent populations located in different regions represents the migrations tens of thousands of years ago of the direct [[patrilineal]] ancestors of current individuals.
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| ===Y-STR haplotypes===
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| Genetic results also include the '''Y-STR haplotype''', the set of results from the Y-STR markers tested.
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| Unlike the UEPs, the Y-STRs mutate much more easily, which allows them to be used to distinguish recent genealogy. But it also means that, rather than the population of descendants of a genetic event all sharing the ''same'' result, the Y-STR haplotypes are likely to have spread apart, to form a ''cluster'' of more or less similar results. Typically, this cluster will have a definite most probable center, the '''[[modal haplotype]]''' (presumably similar to the haplotype of the original founding event), and also a '''haplotype diversity''' — the degree to which it has become spread out. The further in the past the defining event occurred, and the more that subsequent population growth occurred early, the greater the haplotype diversity will be for a particular number of descendants. However, if the haplotype diversity is smaller for a particular number of descendants, this may indicate a more recent common ancestor, or a recent population expansion.
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| It is important to note that, unlike for UEPs, two individuals with a similar Y-STR haplotype may not necessarily share a similar ancestry. Y-STR events are not unique. Instead, the clusters of Y-STR haplotype results inherited from different events and different histories tend to overlap.
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| In most cases, it is a long time since the haplogroups' defining events, so typically the cluster of Y-STR haplotype results associated with descendents of that event has become rather broad. These results will tend to significantly overlap the (similarly broad) clusters of Y-STR haplotypes associated with other haplogroups. This makes it impossible for researchers to predict with absolute certainty to which Y-DNA haplogroup a Y-STR haplotype would point. If the UEPs are not tested, the Y-STRs may be used only to predict probabilities for haplogroup ancestry, but not certainties.
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| A similar scenario exists in trying to evaluate whether shared surnames indicate shared genetic ancestry. A cluster of similar Y-STR haplotypes may indicate a shared common ancestor, with an identifiable modal haplotype, but only if the cluster is sufficiently distinct from what may have happened by chance from different individuals who historically adopted the same name independently. Many names were adopted from common occupations, for instance, or were associated with habitation of particular sites. More extensive haplotype typing is needed to establish genetic genealogy. Commercial DNA-testing companies now offer their customers testing of more numerous sets of markers to improve definition of their genetic ancestry. The number of sets of markers tested has increased from 12 during the early years to 111 more recently.
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| Establishing plausible relatedness between different surnames data-mined from a database is significantly more difficult. The researcher must establish that the ''very nearest'' member of the population in question, chosen purposely from the population for that reason, would be unlikely to match by accident. This is more than establishing that a ''randomly selected'' member of the population is unlikely to have such a close match by accident. Because of the difficulty, establishing relatedness between different surnames as in such a scenario is likely to be impossible, except in special cases where there is specific information to drastically limit the size of the population of candidates under consideration.
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| ==Diversity==
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| Haplotype diversity is a measure of the uniqueness of a particular haplotype in a given population. The haplotype diversity (H) is computed as:<ref>Masatoshi Nei and Fumio Tajima, "DNA polymorphism detectable by restriction endonucleases", Genetics 97:145 (1981)</ref><br>
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| <math>H=\frac{N}{N-1}(1- \sum_{i}x_i^2)</math><br>
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| where <math>x_i</math> is the (relative) haplotype frequency of each haplotype in the sample and <math>N</math> is the sample size. Haplotype diversity is given for each sample.
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| ==See also==
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| * [[Haplotype estimation]]
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| * [[International HapMap Project]]
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| * [[Genealogical DNA test]]
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| * [[Haplogroup]]
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| * [[Y-STR]]
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| ==Software==
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| * [http://famhap.meb.uni-bonn.de/ FAMHAP]<ref>{{cite journal|author=Becker T., Knapp M.|title=Maximum-likelihood estimation of haplotype frequencies in nuclear families|journal=Genetic Epidemiology|year=2004|volume=27|pages=21–32|pmid=15185400|doi=10.1002/gepi.10323|issue=1}}</ref> — FAMHAP is a software for single-marker analysis and, in particular, joint analysis of unphased genotype data from tightly linked markers (haplotype analysis).
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| * [http://www.sph.umich.edu/csg/abecasis/fugue/index.html Fugue] — [[EM algorithm|EM]] based haplotype estimation and association tests in unrelated and nuclear families.
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| * [http://cdsweb01.fhcrc.org/HPlus/ HPlus]<ref>{{cite journal|author=Li S.S., Khalid N., Carlson C., Zhao L.P.|title=Estimating haplotype frequencies and standard errors for multiple single nucleotide polymorphisms|journal=Biostatistics|year=2003|volume=4|pages=513–522|url=http://biostatistics.oxfordjournals.org/cgi/content/abstract/4/4/513|pmid=14557108|doi=10.1093/biostatistics/4.4.513|issue=4}}</ref> — A software package for imputation and testing of haplotypes in association studies using a modified method that incorporates the expectation-maximization algorithm and a Bayesian method known as progressive ligation.
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| * [http://cgi.uc.edu/cgi-bin/kzhang/haploBlockFinder.cgi/ HaploBlockFinder] — A software package for analyses of haplotype block structure.
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| * [http://familygenomics.systemsbiology.net/node/376 Haploscribe]<ref>{{cite journal|author=Roach J.C., Glusman G., Hubley R., Montsaroff S.Z., Holloway A.K., Mauldin D.E., Srivastava D., Garg V., Pollard K.S., Galas D.J., Hood L., Smit A.F.A.|title=Chromosomal Haplotypes by Genetic Phasing of Human Families|journal=American Journal of Human Genetics|year=2011|volume=89|pages=382–397|url=http://www.cell.com/AJHG/abstract/S0002-9297%2811%2900318-1|doi=10.1016/j.ajhg.2011.07.023|pmid= 21855840|issue=3}}</ref> — Reconstruction of whole-chromosome haplotypes based on all genotyped positions in a nuclear family, including rare variants.
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| * [[Haploview]]<ref>{{cite journal|author=Barrett J.C., Fry B., Maller J., Daly M.J.|title=Haploview: analysis and visualization of LD and haplotype maps|journal=Bioinformatics|year=2005|volume=21|pages=263–265|url=http://bioinformatics.oxfordjournals.org/cgi/reprint/21/2/263|doi=10.1093/bioinformatics/bth457|pmid=15297300|issue=2}}</ref> — Visualisation of [[linkage disequilibrium]], haplotype estimation and haplotype tagging ([http://www.broad.mit.edu/mpg/haploview/ Homepage]).
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| * [http://www.goldenhelix.com/SNP_Variation/HelixTree/haplotype_trend_regression.html HelixTree] — Haplotype analysis software - Haplotype Trend Regression (HTR), haplotypic association tests, and haplotype frequency estimation using both the expectation-maximization (EM) algorithm and composite haplotype method (CHM).
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| * [http://www.stat.washington.edu/stephens/software.html PHASE] — A software for haplotype reconstruction, and recombination rate estimation from population data.
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| * [http://www.shapeit.fr/ SHAPEIT]<ref>{{cite journal|author=Delaneau O, Zagury J-F, Marchini J |title=Improved whole chromosome phasing for disease and population genetic studies. |journal=Nature Methods|year=2013|volume=10|pages=5–6|doi=10.1038/nmeth.2307}}</ref> — SHAPEIT2 is a program for haplotype estimation of SNP genotypes in large cohorts across whole chromosome.
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| * [http://www-gene.cimr.cam.ac.uk/clayton/software/ SNPHAP] — [[EM algorithm|EM]] based software for estimating haplotype frequencies from unphased genotypes.
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| * [http://pngu.mgh.harvard.edu/purcell/whap/ WHAP]<ref>{{cite journal|author=Purcell S., Daly M. J., Sham P. C.|title=WHAP: haplotype-based association analysis|journal=Bioinformatics|year=2007|volume=23|pages=255–256|url=http://bioinformatics.oxfordjournals.org/cgi/reprint/23/2/255|doi=10.1093/bioinformatics/btl580|pmid=17118959|issue=2}}</ref> — ''haplotype'' based association analysis.
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| ==References==
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| <references/>
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| ==External links==
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| * [http://www.haplogroups.com HaploGroups.com] — Comprehensive resource for DNA testing.
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| * [http://www.hapmap.org/ HapMap] — homepage for the International HapMap Project.
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| * [http://www.kerchner.com/haplotypevshaplogroup.htm Haplotype versus Haplogroup] — the difference between haplogroup & haplotype explained.
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| [[Category:Classical genetics]]
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| [[Category:Population genetics]]
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| [[Category:Genetic genealogy]]
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