Editing Identity by descent (section)

== Applications ==
Identified IBD segments can be used for a wide range of purposes. As noted above the amount (length and number) of IBD sharing depends on the familial relationships between the tested individuals. Therefore, one application of IBD segment detection is to quantify relatedness.<ref name="Albrechtsen.2009">{{Cite journal
| last1 = Albrechtsen | first1 = A.
| last2 = Sand Korneliussen | first2 = T.
| last3 = Moltke | first3 = I.
| last4 = Van Overseem Hansen | first4 = T.
| last5 = Nielsen | first5 = F. C.
| last6 = Nielsen | first6 = R.
| doi = 10.1002/gepi.20378
| title = Relatedness mapping and tracts of relatedness for genome-wide data in the presence of linkage disequilibrium
| journal = Genetic Epidemiology
| volume = 33
| issue = 3
| pages = 266–274
| year = 2009
| pmid = 19025785
| pmc =
| s2cid = 12029712
}}</ref><ref name="Browning.2010">{{Cite journal
| last1 = Browning | first1 = S. R.
| last2 = Browning | first2 = B. L.
| doi = 10.1016/j.ajhg.2010.02.021
| title = High-Resolution Detection of Identity by Descent in Unrelated Individuals
| journal = The American Journal of Human Genetics
| volume = 86
| issue = 4
| pages = 526–539
| year = 2010
| pmid = 20303063
| pmc =2850444
}}</ref><ref name="Gusev.2009">{{Cite journal
| last1 = Gusev | first1 = A.
| last2 = Lowe | first2 = J. K.
| last3 = Stoffel | first3 = M.
| last4 = Daly | first4 = M. J.
| last5 = Altshuler | first5 = D.
| last6 = Breslow | first6 = J. L.
| last7 = Friedman | first7 = J. M.
| last8 = Pe'Er | first8 = I.
| doi = 10.1101/gr.081398.108
| title = Whole population, genome-wide mapping of hidden relatedness
| journal = Genome Research
| volume = 19
| issue = 2
| pages = 318–326
| year = 2008
| pmid = 18971310
| pmc =2652213
}}</ref><ref name="Purcell.2007">{{Cite journal
| last1 = Purcell | first1 = S.
| last2 = Neale | first2 = B.
| last3 = Todd-Brown | first3 = K.
| last4 = Thomas | first4 = L.
| last5 = Ferreira | first5 = M. A. R.
| last6 = Bender | first6 = D.
| last7 = Maller | first7 = J.
| last8 = Sklar | first8 = P.
| last9 = De Bakker | first9 = P. I. W.
| last10 = Daly | first10 = M. J.
| last11 = Sham | first11 = P. C.
| doi = 10.1086/519795
| title = PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
| journal = The American Journal of Human Genetics
| volume = 81
| issue = 3
| pages = 559–575
| year = 2007
| pmid = 17701901
| pmc =1950838
}}</ref> Measurement of relatedness can be used in [[forensic genetics]],<ref name="Evett.1998">{{cite book|author1=Ian W. Evett|author2=Bruce S. Weir|title=Interpreting DNA Evidence: Statistical Genetics for Forensic Scientists|url=https://books.google.com/books?id=J1V3QgAACAAJ|date=January 1998|publisher=Sinauer Associates, Incorporated|isbn=978-0-87893-155-2}}</ref> but can also increase information in [[genetic linkage]] mapping<ref name=" Albrechtsen.2009"/><ref name="Leutenegger.2003">{{Cite journal
| last1 = Leutenegger | first1 = A.
| last2 = Prum | first2 = B.
| last3 = Genin | first3 = E.
| last4 = Verny | first4 = C.
| last5 = Lemainque | first5 = A.
| last6 = Clergetdarpoux | first6 = F.
| last7 = Thompson | first7 = E. | author7-link = Elizabeth A. Thompson
| doi = 10.1086/378207
| title = Estimation of the Inbreeding Coefficient through Use of Genomic Data
| journal = The American Journal of Human Genetics
| volume = 73
| issue = 3
| pages = 516–523
| year = 2003
| pmid = 12900793
| pmc =1180677
}}</ref> and help to decrease [[Bias (statistics)|bias]] by undocumented relationships in standard [[Genetic association|association studies]].<ref name="Purcell.2007"/><ref name="Voight.2005">{{Cite journal
| last1 = Voight | first1 = B. F.
| last2 = Pritchard | first2 = J. K.
| doi = 10.1371/journal.pgen.0010032
| title = Confounding from Cryptic Relatedness in Case-Control Association Studies
| journal = PLOS Genetics
| volume = 1
| issue = 3
| pages = e32
| year = 2005
| pmid = 16151517
| pmc =1200427
| doi-access = free
}}</ref>
Another application of IBD is [[Imputation (genetics)|genotype imputation]] and [[haplotype]] [[Gametic phase|phase]] inference.<ref name="Kong.2008">{{Cite journal
| last1 = Kong | first1 = A.
| last2 = Masson | first2 = G.
| last3 = Frigge | first3 = M. L.
| last4 = Gylfason | first4 = A.
| last5 = Zusmanovich | first5 = P.
| last6 = Thorleifsson | first6 = G.
| last7 = Olason | first7 = P. I.
| last8 = Ingason | first8 = A.
| last9 = Steinberg | first9 = S.
| last10 = Rafnar | first10 = T.
| last11 = Sulem | first11 = P.
| last12 = Mouy | first12 = M.
| last13 = Jonsson | first13 = F.
| last14 = Thorsteinsdottir | first14 = U.
| last15 = Gudbjartsson | first15 = D. F.
| last16 = Stefansson | first16 = H.
| last17 = Stefansson | first17 = K.
| title = Detection of sharing by descent, long-range phasing and haplotype imputation
| doi = 10.1038/ng.216
| journal = Nature Genetics
| volume = 40
| issue = 9
| pages = 1068–1075
| year = 2008
| pmid = 19165921
| pmc = 4540081}}</ref><ref name="Gusev.2012">{{Cite journal
| last1 = Gusev | first1 = A.
| last2 = Shah | first2 = M. J.
| last3 = Kenny | first3 = E. E.
| last4 = Ramachandran | first4 = A.
| last5 = Lowe | first5 = J. K.
| last6 = Salit | first6 = J.
| last7 = Lee | first7 = C. C.
| last8 = Levandowsky | first8 = E. C.
| last9 = Weaver | first9 = T. N.
| last10 = Doan | first10 = Q. C.
| last11 = Peckham | first11 = H. E.
| last12 = McLaughlin | first12 = S. F.
| last13 = Lyons | first13 = M. R.
| last14 = Sheth | first14 = V. N.
| last15 = Stoffel | first15 = M.
| last16 = De La Vega | first16 = F. M.
| last17 = Friedman | first17 = J. M.
| last18 = Breslow | first18 = J. L.
| last19 = Pe'Er | first19 = I.
| title = Low-Pass Genome-Wide Sequencing and Variant Inference Using Identity-by-Descent in an Isolated Human Population
| doi = 10.1534/genetics.111.134874
| journal = Genetics
| volume = 190
| issue = 2
| pages = 679–689
| year = 2011
| pmid = 22135348
| pmc =3276614
}}</ref><ref name="Browning.2009">{{Cite journal
| last1 = Browning | first1 = B. L.
| last2 = Browning | first2 = S. R.
| doi = 10.1016/j.ajhg.2009.01.005
| title = A Unified Approach to Genotype Imputation and Haplotype-Phase Inference for Large Data Sets of Trios and Unrelated Individuals
| journal = The American Journal of Human Genetics
| volume = 84
| issue = 2
| pages = 210–223
| year = 2009
| pmid = 19200528
| pmc =2668004
}}</ref> Long shared segments of IBD, which are broken up by short regions may be indicative for phasing errors.<ref name="Gusev.2009"/><ref name="Hochreiter.2013"/>{{rp|SI}}

=== IBD mapping ===
IBD mapping<ref name=" Albrechtsen.2009"/> is similar to linkage analysis, but can be performed without a known pedigree on a cohort of unrelated individuals. IBD mapping can be seen as a new form of association analysis that increases the [[Statistical power|power]] to map genes or genomic regions containing multiple rare disease susceptibility variants.<ref name="Purcell.2007"/><ref name="Browning.2012b">{{Cite journal
| last1 = Browning | first1 = S. R.
| last2 = Thompson | first2 = E. A.  | author2-link = Elizabeth A. Thompson
| doi = 10.1534/genetics.111.136937
| title = Detecting Rare Variant Associations by Identity-by-Descent Mapping in Case-Control Studies
| journal = Genetics
| volume = 190
| issue = 4
| pages = 1521–1531
| year = 2012
| pmid = 22267498
| pmc =3316661
}}</ref>

Using simulated data, Browning and [[Elizabeth A. Thompson|Thompson]] showed that IBD mapping has higher power than association testing when multiple rare variants within a gene contribute to disease susceptibility.<ref name="Browning.2012b"/> Via IBD mapping, genome-wide [[Statistical significance|significant]] regions in isolated populations as well as outbred populations were found while standard association tests failed.<ref name="Gusev.2012"/><ref name="Gusev.2011">{{Cite journal
| last1 = Gusev | first1 = A.
| last2 = Kenny | first2 = E. E.
| last3 = Lowe | first3 = J. K.
| last4 = Salit | first4 = J.
| last5 = Saxena | first5 = R.
| last6 = Kathiresan | first6 = S.
| last7 = Altshuler | first7 = D. M.
| last8 = Friedman | first8 = J. M.
| last9 = Breslow | first9 = J. L.
| last10 = Pe'Er | first10 = I.
| doi = 10.1016/j.ajhg.2011.04.023
| title = DASH: A Method for Identical-by-Descent Haplotype Mapping Uncovers Association with Recent Variation
| journal = The American Journal of Human Genetics
| volume = 88
| issue = 6
| pages = 706–717
| year = 2011
| pmid = 21620352
| pmc =3113343
}}</ref> Houwen et al. used IBD sharing to identify the chromosomal location of a gene responsible for benign recurrent intrahepatic [[cholestasis]] in an isolated fishing population.<ref name="Houwen.1994">{{Cite journal
| last1 = Houwen | first1 = R. H. J.
| last2 = Baharloo | first2 = S.
| last3 = Blankenship | first3 = K.
| last4 = Raeymaekers | first4 = P.
| last5 = Juyn | first5 = J.
| last6 = Sandkuijl | first6 = L. A.
| last7 = Freimer | first7 = N. B.
| doi = 10.1038/ng1294-380
| title = Genome screening by searching for shared segments: Mapping a gene for benign recurrent intrahepatic cholestasis
| journal = Nature Genetics
| volume = 8
| issue = 4
| pages = 380–386
| year = 1994
| pmid = 7894490
| pmc =
| hdl = 1765/55192
| s2cid = 8131209
| url = http://repub.eur.nl/pub/55192
| hdl-access = free
}}</ref> Kenny et al. also used an isolated population to fine-map a signal found by a [[genome-wide association study]] (GWAS) of plasma [[plant sterol]] (PPS) levels, a surrogate measure of cholesterol absorption from the intestine.<ref name="Kenny.2009">{{Cite journal
| last1 = Kenny | first1 = E. E.
| last2 = Gusev | first2 = A.
| last3 = Riegel | first3 = K.
| last4 = Lutjohann | first4 = D.
| last5 = Lowe | first5 = J. K.
| last6 = Salit | first6 = J.
| last7 = Maller | first7 = J. B.
| last8 = Stoffel | first8 = M.
| last9 = Daly | first9 = M. J.
| last10 = Altshuler | first10 = D. M.
| last11 = Friedman | first11 = J. M.
| last12 = Breslow | first12 = J. L.
| last13 = Pe'Er | first13 = I.
| last14 = Sehayek | first14 = E.
| title = Systematic haplotype analysis resolves a complex plasma plant sterol locus on the Micronesian Island of Kosrae
| doi = 10.1073/pnas.0907336106
| journal = Proceedings of the National Academy of Sciences
| volume = 106
| issue = 33
| pages = 13886–13891
| year = 2009
| pmid = 19667188
| pmc =2728990
| bibcode = 2009PNAS..10613886K
| doi-access = free
}}</ref> Francks et al. was able to identify a potential susceptibility locus for [[schizophrenia]] and [[bipolar disorder]] with genotype data of case-control samples.<ref name="Francks.2008">{{Cite journal
| last1 = Francks | first1 = C.
| last2 = Tozzi | first2 = F.
| last3 = Farmer | first3 = A.
| last4 = Vincent | first4 = J. B.
| last5 = Rujescu | first5 = D.
| last6 = St Clair | first6 = D.
| last7 = Muglia | first7 = P.
| doi = 10.1038/mp.2008.100
| title = Population-based linkage analysis of schizophrenia and bipolar case–control cohorts identifies a potential susceptibility locus on 19q13
| journal = Molecular Psychiatry
| volume = 15
| issue = 3
| pages = 319–325
| year = 2008
| pmid = 18794890
| pmc =
| doi-access = free
| hdl = 11858/00-001M-0000-0012-C935-9
| hdl-access = free
}}</ref> Lin et al. found a genome-wide significant linkage signal in a dataset of [[multiple sclerosis]] patients.<ref name="Lin.2013">{{Cite journal
| last1 = Lin | first1 = R.
| last2 = Charlesworth | first2 = J.
| last3 = Stankovich | first3 = J.
| last4 = Perreau | first4 = V. M.
| last5 = Brown | first5 = M. A.
| last6 = Anzgene | first6 = B. V.
| last7 = Taylor | first7 = B. V.
| editor1-last = Toland
| editor1-first = Amanda Ewart
| title = Identity-by-Descent Mapping to Detect Rare Variants Conferring Susceptibility to Multiple Sclerosis
| doi = 10.1371/journal.pone.0056379
| journal = PLOS ONE
| volume = 8
| issue = 3
| pages = e56379
| year = 2013
| pmid = 23472070
| pmc =3589405
| bibcode = 2013PLoSO...856379L
| doi-access = free
}}</ref> Letouzé et al. used IBD mapping to look for [[founder mutation]]s in [[cancer]] samples.<ref name="Letouze.2012">{{Cite journal
| last1 = Letouzé | first1 = E.
| last2 = Sow | first2 = A.
| last3 = Petel | first3 = F.
| last4 = Rosati | first4 = R.
| last5 = Figueiredo | first5 = B. C.
| last6 = Burnichon | first6 = N.
| last7 = Gimenez-Roqueplo | first7 = A. P.
| last8 = Lalli | first8 = E.
| last9 = De Reyniès | first9 = A. L.
| editor1-last = Mailund
| editor1-first = Thomas
| title = Identity by Descent Mapping of Founder Mutations in Cancer Using High-Resolution Tumor SNP Data
| doi = 10.1371/journal.pone.0035897
| journal = PLOS ONE
| volume = 7
| issue = 5
| pages = e35897
| year = 2012
| pmid = 22567117
| pmc =3342326
| bibcode = 2012PLoSO...735897L
| doi-access = free
}}</ref>

[[File:IBD segment detected by HapFABIA in 1000Genomes.png|thumb|upright=2.0|alt=An IBD segment identified by HapFABIA in the 1000 Genomes|An IBD segment identified by HapFABIA in Asian genomes. Rare single nucleotide variants (SNVs) that tag the IBD segment are coloured purple. Below the turquoise bar, the IBD segment in ancient genomes is displayed.]]

=== IBD in population genetics ===
Detection of [[natural selection]] in the human genome is also possible via detected IBD segments. Selection will usually tend to increase the number of IBD segments among individuals in a population. By scanning for regions with excess IBD sharing, regions in the human genome that have been under strong, very recent selection can be identified.<ref name="Albrechtsen.2010">{{Cite journal
| last1 = Albrechtsen | first1 = A.
| last2 = Moltke | first2 = I.
| last3 = Nielsen | first3 = R.
| doi = 10.1534/genetics.110.113977
| title = Natural Selection and the Distribution of Identity-by-Descent in the Human Genome
| journal = Genetics
| volume = 186
| issue = 1
| pages = 295–308
| year = 2010
| pmid = 20592267
| pmc =2940294
}}</ref><ref name="Han.2013">{{Cite journal
| last1 = Han | first1 = L.
| last2 = Abney | first2 = M.
| doi = 10.1002/gepi.20606
| title = Identity by descent estimation with dense genome-wide genotype data
| journal = Genetic Epidemiology
| volume = 35
| issue = 6
| pages = 557–567
| year = 2011
| pmid = 21769932
| pmc =3587128
}}</ref>

In addition to that, IBD segments can be useful for measuring and identifying other influences on population structure.<ref name="Purcell.2007"/><ref name="Cockerham.1983">{{Cite journal
| last1 = Cockerham | first1 = C. C.
| last2 = Weir | first2 = B. S.
| title = Variance of actual inbreeding
| journal = Theoretical Population Biology
| volume = 23
| issue = 1
| pages = 85–109
| year = 1983
| pmid = 6857551
 | doi=10.1016/0040-5809(83)90006-0
| bibcode = 1983TPBio..23...85C
}}</ref><ref name="Gusev.2012b">{{Cite journal
| last1 = Gusev | first1 = A.
| last2 = Palamara | first2 = P. F.
| last3 = Aponte | first3 = G.
| last4 = Zhuang | first4 = Z.
| last5 = Darvasi | first5 = A.
| last6 = Gregersen | first6 = P.
| last7 = Pe'Er | first7 = I.
| doi = 10.1093/molbev/msr133
| title = The Architecture of Long-Range Haplotypes Shared within and across Populations
| journal = Molecular Biology and Evolution
| volume = 29
| issue = 2
| pages = 473–486
| year = 2011
| pmid = 21984068
| pmc =3350316
}}</ref><ref name="Palamara.2012">{{Cite journal
| last1 = Palamara | first1 = P. F.
| last2 = Lencz | first2 = T.
| last3 = Darvasi | first3 = A.
| last4 = Pe’Er | first4 = I.
| title = Length Distributions of Identity by Descent Reveal Fine-Scale Demographic History
| doi = 10.1016/j.ajhg.2012.08.030
| journal = The American Journal of Human Genetics
| volume = 91
| issue = 5
| pages = 809–822
| year = 2012
| pmid = 23103233
| pmc =3487132
}}</ref><ref name="Palamara.2013">{{Cite journal
| last1 = Palamara | first1 = P. F.
| last2 = Pe'Er | first2 = I.
| doi = 10.1093/bioinformatics/btt239
| title = Inference of historical migration rates via haplotype sharing
| journal = Bioinformatics
| volume = 29
| issue = 13
| pages = i180–i188
| year = 2013
| pmid = 23812983
| pmc =3694674
}}</ref> Gusev et al. showed that IBD segments can be used with additional modeling to estimate demographic history including [[Population bottleneck|bottlenecks]] and [[Genetic admixture|admixture]].<ref name="Gusev.2012b"/> Using similar models Palamara et al. and Carmi et al. reconstructed the [[Historical demography|demographic history]] of [[Ashkenazi Jewish]] and Kenyan [[Maasai people|Maasai]] individuals.<ref name="Palamara.2012"/><ref name="Palamara.2013"/><ref name="Carmi.2013">{{Cite journal
| last1 = Carmi | first1 = S.
| last2 = Palamara | first2 = P. F.
| last3 = Vacic | first3 = V.
| last4 = Lencz | first4 = T.
| last5 = Darvasi | first5 = A.
| last6 = Pe'Er | first6 = I.
| doi = 10.1534/genetics.112.147215
| title = The Variance of Identity-by-Descent Sharing in the Wright-Fisher Model
| journal = Genetics
| volume = 193
| issue = 3
| pages = 911–928
| year = 2013
| pmid = 23267057
| pmc =3584006
| arxiv = 1206.4745
}}</ref> Botigué et al. investigated differences in African ancestry among European populations.<ref name="Botigue.2013">{{Cite journal
| last1 = Botigue | first1 = L. R.
| last2 = Henn | first2 = B. M.
| last3 = Gravel | first3 = S.
| last4 = Maples | first4 = B. K.
| last5 = Gignoux | first5 = C. R.
| last6 = Corona | first6 = E.
| last7 = Atzmon | first7 = G.
| last8 = Burns | first8 = E.
| last9 = Ostrer | first9 = H.
| last10 = Flores | first10 = C.
| last11 = Bertranpetit | first11 = J.
| last12 = Comas | first12 = D.
| last13 = Bustamante | first13 = C. D.
| title = Gene flow from North Africa contributes to differential human genetic diversity in southern Europe
| doi = 10.1073/pnas.1306223110
| journal = Proceedings of the National Academy of Sciences
| volume = 110
| issue = 29
| pages = 11791–11796
| year = 2013
| pmid = 23733930
| pmc =3718088
| bibcode = 2013PNAS..11011791B
| doi-access = free
}}</ref> Ralph and Coop used IBD detection to quantify the common ancestry of different European populations<ref name="Ralph.2013">{{Cite journal
| last1 = Ralph | first1 = P.
| last2 = Coop | first2 = G.
| editor1-last = Tyler-Smith
| editor1-first = Chris
| doi = 10.1371/journal.pbio.1001555
| title = The Geography of Recent Genetic Ancestry across Europe
| journal = PLOS Biology
| volume = 11
| issue = 5
| pages = e1001555
| year = 2013
| pmid = 23667324
| pmc =3646727
| doi-access = free
}}</ref> and Gravel et al. similarly tried to draw conclusions of the genetic history of populations in the Americas.<ref name=" Gravel.2013">{{Cite journal
| last1 = Gravel | first1 = S.
| last2 = Zakharia | first2 = F.
| last3 = Moreno-Estrada | first3 = A.
| last4 = Byrnes | first4 = J. K.
| last5 = Muzzio | first5 = M.
| last6 = Rodriguez-Flores | first6 = J. L.
| last7 = Kenny | first7 = E. E.
| last8 = Gignoux | first8 = C. R.
| last9 = Maples | first9 = B. K.
| last10 = Guiblet | first10 = W.
| last11 = Dutil | first11 = J.
| last12 = Via | first12 = M.
| last13 = Sandoval | first13 = K.
| last14 = Bedoya | first14 = G.
| last15 = 1000 Genomes | first15 = T. K.
| last16 = Oleksyk | first16 = A.
| last17 = Ruiz-Linares | first17 = E. G.
| last18 = Burchard | first18 = J. C.
| last19 = Martinez-Cruzado | first19 = C. D.
| last20 = Bustamante | first20 = C. D.
| editor1-last = Williams
| editor1-first = Scott M
| title = Reconstructing Native American Migrations from Whole-Genome and Whole-Exome Data
| doi = 10.1371/journal.pgen.1004023
| journal = PLOS Genetics
| volume = 9
| issue = 12
| pages = e1004023
| year = 2013
| pmid = 24385924
| pmc =3873240
| arxiv = 1306.4021
| doi-access = free
}}</ref> Ringbauer et al. utilized geographic structure of IBD segments to estimate dispersal within Eastern Europe during the last centuries.<ref>{{Cite journal|last1=Ringbauer|first1=Harald|last2=Coop|first2=Graham|last3=Barton|first3=Nicholas H.|date=2017-03-01|title=Inferring Recent Demography from Isolation by Distance of Long Shared Sequence Blocks|url=http://www.genetics.org/content/205/3/1335|journal=Genetics|language=en|volume=205|issue=3|pages=1335–1351|doi=10.1534/genetics.116.196220|issn=0016-6731|pmid=28108588|pmc=5340342}}</ref> Using the [[1000 Genomes Project|1000 Genomes]] data Hochreiter found differences in IBD sharing between African, Asian and European populations as well as IBD segments that are shared with ancient genomes like the [[Neanderthal]] or [[Denisova hominin|Denisova]].<ref name="Hochreiter.2013">{{Cite journal
| last1 = Hochreiter | first1 = S.
| doi = 10.1093/nar/gkt1013
| title = HapFABIA: Identification of very short segments of identity by descent characterized by rare variants in large sequencing data
| journal = Nucleic Acids Research
| year = 2013
| pmid = 24174545
| pmc =3905877| volume=41
 | issue=22
 | pages=e202
}}</ref>