Chicken Chromosome Linkage Map

The following linkage map table was originally created by an outstanding collaborative effort of members of The Coop and is restored here for reference purposes.

Refer to our chicken genetics articles for more information on chicken chromosomes, genes, and their outcomes.

Chromosome 1

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
OBlue Egg-ShellSLCO1B3Wang et al. 2013. [34] , Wragg et al. 2013. [36]
PPea combSOX5 (SRY-box 5)Wright et al. 2009.[1] Sato et al. 2010.[2]
DbDark BrownSOX10 (SRY-box 10)Gunnarsson et al. 2011.[3]
MlMelanoticMl is 45 + map units from P
no close linkage to above
c (cre, ca)Recessive WhiteTYR (Tyrosinase)Chang et al, 2006.[4] Sato et. al, 2007.[5]
(Dutch Bantam)
PRDM16Wu, Zhou et al. [49] Dutch Bantams

Chromosome 2

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
DV, DCDuplex CombEOMES (Eomesodermin)Dorshorst et al 2010.[6]Dorshorst et al 2015.[40]
MMultiple Spurs
Po, PoDPolydactyly, DuplicateLmbr1 (limb region 1)Chromosome 2 – Dorshorst et al 2010.[6]Might be SHH (Sonic HedgeHog) instead of Lmbr1. Dunn et al., 2011.[7]Zhang et al 2016. [42] Further evidence there are 2 different Po genes (Chinese breeds & Sultans different sequence to European breeds Houdan, Dorkings & Faverolles), He et al 2017.[47]
no close linkage to above
RpRumplessIrx1 and Irx2 (Iroquois homeobox)Rooksana et al, 2012.[8]

Chromosome 3

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
Ea-PBlood Group P* new to 3, due to linkage with Na
NaNaked NeckBMP12/GDF7 (bone morphogenetic protein 12)(growth differentiation factor 7)Pitel et al. 2000.[9] Mou et al. 2011.[10]
hHookless – SilkinessPDSS2Feng et al 2014. [39] Dorshorst et al 2010.[6]
FlFlightlesspossible Chromosome 3. Due to close linkage with h – hookless

Chromosome 4

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
mo, mo^wMottled, WhiteEDNRB2(Endothelin Receptor B2)Kinoshita et al. 2014.[38]
no known linkage to above
scScalelessFGF20(Fibroblast growth factor 20)Wells et al. 2012.[33]
4q3.1DwarfismHMGA2Zhou Wu et al. 2021 [49]

Chromosome 6

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
igInhibitor of Gold (Cream)COMTD1(catechol-O-methyltransferase domain containing 1)Eriksson, 2012.[11]

Chromosome 7

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
CpCreeperIHH (Indian hedgehog)Jin et al. 2016.[45]
RRose combMNR2 (homeodomain protein)(& CCDC108 coiled-coil domain containing 108 )Imsland et al. 2012.[12]
UUropygiallinkage not given to lav.
the below not linear
lav32.5LavenderMLPH (melanophilin)lav 32.5 map units to R.Vaez et al., 2008.[13]
?linkage not given between lav & Mp
Mp16Mp 16 map units to R
the above not linearend of linkage group 1
Ade-Badenine synthesis BAde-B in linkage group VIII

Chromosome 8

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
FMO3Fishy taint (eggs & meat)FMO3 (flavincontainingmono-oxygenase 3)Honkatukia et al. 2005.[14]Hamid et al. 2012.[15]

Chromosome 9

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
HRGWhite eggs (brown pigment suppressor)HRG1 (heme-responsive gene-1), Heme Transporter HRG, codes for Histidine-rich glycoproteinPrimary transporters for both protoporphyrinogen and heme. Chuanwei Zheng et al. 2014 [48]

Chromosome 10

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
HfHenny featheringCYP19A1 (cytochrome P450, family 19, subfamily A, polypeptide 1)ref: OMIA

Microchromosome 11

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
EE, ER, ER- Fay, eWh, e+, eb, es, ebc, ey (E series)MC1R(melanocortin-1 receptor)Takeuchi et al. 1996.[16], Kerje et al. 2003.[17]Ling et al. 2003.[18]
E & mo loci 26 cM linkage proposed by Brumbaugh & Hollander, 1965. [19]Further study indicated that this E-mo 26 cM relationship was not repeatable. Ref. Smyth & Ponce de Leon, 1992. [43]mo (EDNRB2) locus found on Chromosome 4 in 2014. Ref. Kinoshita et al. 2014.[38]

Microchromosome 12

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
BlBlueMITF*possible candidate – not sequenced in chickens.Minvielle et al. 2010.[20]
no known linkage to above
loCongenital locoOkumura et al. 2013.[37]

Microchromosome 13

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
PtiFeathered legsChromosome 13 -Dorshorst et al. 2010.[6]

Microchromosome 15

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
EtEar TuftTBX1, partial GNB1L(T-box 1)Rooksana et al, 2012.[8]

Microchromosome 16 (17)

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
R-Rs 1
NORNucleolar organiser region

Microchromosome 20

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
FmFibromelanosisEDN3 (Endothelin 3)Chromosome 20 – Dorshorst et al. 2010.[6]might be EDN3 – not substantiatedDorshorst et al. 2011.[21], Shinomiya et al. 2011.[22]

Microchromosome 24

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
wYellow SkinBCDO2 (beta-carotene dioxygenase 2)Eriksson et al. 2008.[23]
Ea-HBlood Group H

Microchromosome 25

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
?Beak DeformityLOC426217 (claw keratin-like)Bai et al. 2016.[41]

Microchromosome 27

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
MbMuff and BeardHOXB8 (Homeobox B8)Guo et al. 2016.[44]

Microchromosome 33 (Linkage Group E22C19W28)

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
CrCrestHOXC8(Homeobox protein C8)Wang et al. 2012.[24]
I, ID, ISDominant White, Dun, SmokyPMEL17(Melanocyte protein Pmel 17)Kerje et al. 2004.[25]
FFrizzleKRT75(α-Keratin)Ng et al. 2012.[26]

Z Chromosome: sex-linked

LocusMap UnitLocus DescriptionScientific NameComments/ Ref.
roRestricted Ovulator
lnLiver Necrosis
dwB, dwM, dwDwarfGHR (growth hormone receptor)Hull et al. 1999.[27]
pnPrenatal Lethal
ev21Endogenous viral 21EV21 (ALVE21)(Endogenous viral 21)Tixier-Boichard et al. 1997.[28],Bacon et al. 1988.[29]
Kn, Ks, KSlow Feathering / Late FeatheringPRLR and SPEF2(prolactin receptor)(sperm flagellar 2)Elferink et al. 2008.[30]
S, Sal-s, salSilver, Imperfect AlbinismSLC45A2(solute carrier family 45 member 2)Gunnarsson et al, 2007.[31]
lkLady Killer
LiLight Down
yRecessive White Skin or WHAM (Wisconsin hypoalpha mutant)ABCA1 (ATP-binding cassette, sub-family A (ABC1), member 1)Attie et al. 2002. [35]
brBrown Eye
Id, ida, idc,idMDermal Melanin InhibitorVCAN (Versican) or B4GALT1 (beta1,4-Galactosyltransferase)Might be VCAN or B4GALT1 – not substantiated.Dorshorst et al. 2010.[6]
BSd, BSex-linked Dilution, BarringCDKN2A/B(Cyclin-dependent kinas inhibitor 2A/B)Hellström et al. 2010.[32] ,Schwochow Thalmann et al. 2017.[46]
koHead Streak


The following linkage map table is based on the following books:

Additional data was gathered from many scientific journal papers, all of which are cited in the reference section.


Ref. No.YearReferencePaper URL
12009Wright D, Boije H, Meadows JRS, Bed’hom B, Gourichon D, et al. (2009) Copy Number Variation in Intron 1 of SOX5 Causes the Pea-comb Phenotype in Chickens. PLoS Genet 5(6): e1000512. doi:10.1371/journal.pgen.1000512.[Full]
22010Sato S, Otake T, Suzuki C, Uemoto Y, Saburi J, Hashimoto H, Kobayashi E. (2010) Sequence analysis of a pea comb locus on chicken chromosome 1. Animal Genetics. Volume 41, Issue 6, pages 659–661, December 2010.[Abstract]
32011Gunnarsson U, Kerje S, Bed’hom B, Sahlqvist AS, Ekwall O, Tixier-Boichard M, Kämpe O, Andersson L. (2011) The Dark brown plumage color in chickens is caused by an 8.3-kb deletion upstream of SOX10. Pigment Cell Melanoma Res. 2011 Apr;24(2):268-74. doi: 10.1111/j.1755-148X.2011.00825.x. Epub 2011 Jan 25.[Abstract]
42006Chang C, Coville JL, Coquerelle G, Gourichon D, Oulmouden A, and Tixier-Boichard M. (2006) Complete association between a retroviral insertion in the tyrosinase gene and the recessive white mutation in chickens. BMC Genomics. 2006; 7: 19.[Full]
52007Sato S, Otake T, Suzuki C, Saburi J, Kobayashi E. (2007) Mapping of the recessive white locus and analysis of the tyrosinase gene in chickens. Poult Sci. 2007 Oct;86(10):2126-33.[Full]
62010Dorshorst B, Okimoto R, Ashwell C. (2010) Genomic Regions Associated with Dermal Hyperpigmentation, Polydactyly and Other Morphological Traits in the Silkie Chicken. J Hered. 2010 May-Jun;101(3):339-50[Full]
72011Dunn IC, Paton IR, Clelland AK, Sebastian S, Johnson EJ, McTeir L, Windsor D, Sherman A, Sang H, Burt DW, Tickle C, Davey MG. (2011) The chicken polydactyly (Po) locus causes allelic imbalance and ectopic expression of Shh during limb development. Dev Dyn. 2011 May;240(5):1163-72. doi: 10.1002/dvdy.22623. Epub 2011 Apr 4.[Full]
82012Rooksana E. Noorai, Nowlan H. Freese, Lindsay M. Wright, Susan C. Chapman, and Leigh Anne Clark. (2012) Genome-Wide Association Mapping and Identification of Candidate Genes for the Rumpless and Ear-tufted Traits of the Araucana Chicken. PLoS One. 2012; 7(7): e40974.[Full]
92000Pitel F, Berge R, Coquerelle G, Crooijmans RPMA, Groenen MAM, et al. (2000) Mapping the naked neck (NA) and polydactyly (PO) mutants of the chicken with microsatellite molecular markers. Genet Sel Evol 32: 73–86.[Full]
102011Mou C, Pitel F, Gourichon D, Vignoles F, Tzika A, et al. (2011) Cryptic Patterning of Avian Skin Confers a Developmental Facility for Loss of Neck Feathering. PLoS Biol 9(3): e1001028. doi:10.1371/journal.pbio.1001028[Full]
112012Eriksson, J (2012) Genetic and Genomic Studies in Chicken: Assigning Function to Vertebrate Genes. Acta Universitatis Upsaliensis. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 732. 55pp. Uppsala. ISBN 978-91-554-8246-6.[Full]
122012Imsland F, Feng C, Boije H, Bed’hom B, Fillon V, Dorshorst B, Rubin CJ, Liu R, Gao Y, Gu X, Wang Y, Gourichon D, Zody MC, Zecchin W, Vieaud A, Tixier-Boichard M, Hu X, Hallböök F, Li N, Andersson L.(2012) The Rose-comb Mutation in Chickens Constitutes a Structural Rearrangement Causing Both Altered Comb Morphology and Defective Sperm Motility. PLoS Genet. 2012 Jun;8(6):e1002775. Epub 2012 Jun 28.[Full]
132008Vaez M, Follett SA, Bed’hom B, Gourichon D, Tixier-Boichard M, Burke T. (2008) A single point-mutation within the melanophilin gene causes the lavender plumage colour dilution phenotype in the chicken. BMC Genet. 2008 Jan 15;9:7. doi: 10.1186/1471-2156-9-7.[Full]
142005Honkatukia M, Reese K, Preisinger R, Tuiskula-Haavisto M, Weigend S, Roito J, Mäki-Tanila A, Vilkki J. (2005) Fishy taint in chicken eggs is associated with a substitution within a conserved motif of the FMO3 gene. Genomics. 2005 Aug;86(2):225-32.[Full]
152012Hamid MA, Wang X, and Zhao X. (2012) Genotyping of flavin-containing mono-oxygenase 3 (FMO3) gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mismatch amplification mutation assay (MAMA-PCR) in chickens. African Journal of Biotechnology Vol. 11(7), pp. 1823-1828, 24 January, 2012[Full]
161996Takeuchi S, Suzuki H, Yabuuchi M and Takahashi S. (1996) A possible involvement of melanocortin 1-receptor in regulating feather color pigmentation in the chicken. Biochimica et Biophysica Acta (BBA) – Gene Structure and Expression Volume 1308, Issue 2, 14 August 1996, Pages 164-168.[Abstract]
172003Kerje S, Lind J, Schütz K, Jensen P, Andersson L. (2003) Melanocortin 1-receptor (MC1R) mutations are associated with plumage colour in chicken. Anim Genet. 2003 Aug;34(4):241-8.[Abstract]
182003Ling MK, Lagerström MC, Fredriksson R, Okimoto R, Mundy NI, Takeuchi S, Schiöth HB. (2003) Association of feather colour with constitutively active melanocortin 1 receptors in chicken. Eur J Biochem. 2003 Apr;270(7):1441-9.[Full]
191965Brumbaugh, J. A., and W. F. Hollander (1965) A further study of the E pattern locus in the fowl. Iowa State J. of Science, 40; 51-64No online paper.
202010Minvielle F, Bed’hom B, Coville JL, Ito S, Inoue-Murayama M, Gourichon D. (2010) The “silver” Japanese quail and the MITF gene: causal mutation, associated traits and homology with the “blue” chicken plumage. BMC Genet. 2010 Feb 25;11:15. doi: 10.1186/1471-2156-11-15.[Full]
212011Dorshorst B, Molin AM, Rubin CJ, Johansson AM, Strömstedt L, Pham MH, Chen CF, Hallböök F, Ashwell C, Andersson L. (2011) A complex genomic rearrangement involving the endothelin 3 locus causes dermal hyperpigmentation in the chicken. PLoS Genet. 2011 Dec;7(12):e1002412. Epub 2011 Dec 22.[Full]
222011Shinomiya A, Kayashima Y, Kinoshita K, Mizutani M, Namikawa T, Matsuda Y, Akiyama T. (2011) Gene Duplication of endothelin 3 is Closely Correlated with the Hyperpigmentation of the Internal Organs (Fibromelanosis) in Silky Chickens. Genetics. 2012 Feb;190(2):627-38. doi: 10.1534/genetics.111.136705. Epub 2011 Nov 30.[Full]
232008Eriksson J, Larson G, Gunnarsson U, Bed’hom B, Tixier-Boichard M, et al. (2008) Identification of the Yellow Skin Gene Reveals a Hybrid Origin of the Domestic Chicken. PLoS Genet 4(2): e1000010. doi:10.1371/journal.pgen.1000010.[Full]
242012Wang Y, Gao Y, Imsland F, Gu X, Feng C, et al. (2012) The Crest Phenotype in Chicken Is Associated with Ectopic Expression of HOXC8 in Cranial Skin. PLoS ONE 7(4): e34012. doi:10.1371/journal.pone.0034012.[Abstract]
252004Kerje S, Sharma P, Gunnarsson U, Kim H, Bagchi S, Fredriksson R, Schütz K, Jensen P, von Heijne G, Okimoto R, Andersson L. (2004) The Dominant white, Dun and Smoky color variants in chicken are associated with insertion/deletion polymorphisms in the PMEL17 gene. Genetics. 2004 Nov;168(3):1507-18.[Full]
262012Ng CS, Wu P, Foley J, Foley A, McDonald ML, Juan WT, Huang CJ, Lai YT, Lo WS, Chen CF, Leal SM, Zhang H, Widelitz RB, Patel PI, Li WH, Chuong CM. (2012) The Chicken Frizzle Feather Is Due to an a-Keratin (KRT75) Mutation That Causes a Defective Rachis. PLoS Genet. 2012 Jul;8(7):e1002748. Epub 2012 Jul 19.[Full]
271999Hull, K.L, Marsh, J.A. and Harvey, S. (1999) A missense mutation in the GHR gene of Cornell sex-linked dwarf chickens does not abolish serum GH binding. Journal of Endocrinology (1999) 161, 495–50.[Full]
281997Tixier-Boichard M, Boulliou-Robic A, Morisson M, Coquerelle G, Horst P, Benkel B. (1997) A deleted retroviral insertion at the ev21-K complex locus in Indonesian chickens. Poult Sci. 1997 May;76(5):733-42[Full]
291988Bacon LD, Smith E, Crittenden LB, Havenstein GB. (1988) Association of the slow feathering (K) and an endogenous viral (ev21) gene on the Z chromosome of chickens. Poult Sci. 1988 Feb;67(2):191-7[Abstract]
302008Elferink MG, Vallée AA, Jungerius AP, Crooijmans RP, Groenen MA. (2008) Partial duplication of the PRLR and SPEF2 genes at the late feathering locus in chicken. BMC Genomics. 2008 Aug 20;9:391.[Full]
312007Gunnarsson U, Hellström AR, Tixier-Boichard M, Minvielle F, Bed’hom B, Ito S, Jensen P, Rattink A, Vereijken A, Andersson L. (2007). Mutations in SLC45A2 Cause Plumage Color Variation in Chicken and Japanese Quail. Genetics. 175, 867-77.[Full]
322010Hellström AR, Sundström E, Gunnarsson U, Bed’Hom B, Tixier-Boichard M, Honaker CF, Sahlqvist AS, Jensen P, Kämpe O, Siegel PB, Kerje S, Andersson L. (2010) Sex-linked barring in chickens is controlled by the CDKN2A /B tumour suppressor locus. Pigment Cell Melanoma Res. 2010 Aug;23(4):521-30. doi: 10.1111/j.1755-148X.2010.00700.x. Epub 2010 Mar 29.[Full]
332012Wells KL, Hadad Y, Ben-Avraham D, Hillel J, Cahaner A and Heado DJ. (2012) Genome-wide SNP scan of pooled DNA reveals nonsense mutation in FGF20 in the scaleless line of featherless chickens. BMC Genomics 2012, 13:257 doi:10.1186/1471-2164-13-257.[Full]
342013Wang Z, Qu L, Yao J, Yang X, Li G, Zhang Y, Li J, Wang X, Bai J, Xu G, Deng X, Yang N, Wu C. (2013) An EAV-HP Insertion in 5′ Flanking Region of SLCO1B3 Causes Blue Eggshell in the Chicken. PLoS Genet. 2013 January; 9(1): e1003183.[Full]
352002Attie, A. D., Hamon, Y., Brooks-Wilson, A.R., Gray-Keller, M.P., MacDonald, M.L.E., Rigot, V., Tebon, A., Zhang, L., Mulligan, J.D., Singaraja, R.R., Bitgood, J.J., Cook M.E., Kastelein, J.J.P., Chimini, G. and Hayden, M. R. (2002) Identification and functional analysis of a naturally occurring E89K mutation in the ABCA1 gene of the WHAM chicken. The Journal of Lipid Research, October 2002. 43, 1610-1617.[Full]
362013Wragg D, Mwacharo JM, Alcalde JA, Wang C, Han J-L, Gongora J, Gourichon D, Tixier-Boichard M, Hanotte O. (2013) Endogenous Retrovirus EAV-HP Linked to Blue Egg Phenotype in Mapuche Fowl. PLoS ONE 8(8): e71393. doi:10.1371/journal.pone.0071393[Full]
372013Okumura, Y., Ohtake, T., Uemoto, Y., Sato, S., Sato, S. and Kobayashi, E. (2013) Fine mapping of the chicken congenital loco locus on chromosome 12. Animal Genetics. doi: 10.1111/age.12065[Abstract]
382014Kinoshita K, Akiyama T, Mizutani M, Shinomiya A, Ishikawa A, et al. (2014) Endothelin Receptor B2 (EDNRB2) Is Responsible for the Tyrosinase-Independent Recessive White (mow) and Mottled (mo) Plumage Phenotypes in the Chicken. PLoS ONE 9(1): e86361. doi:10.1371/journal.pone.0086361[Full]
392014Feng, C., Gao, Y., Dorshorst, B., Song, C., Gu, X., Li, Q., Li, N. et al. (2014) A cis-Regulatory Mutation of PDSS2 Causes Silky-Feather in Chickens. PLoS Genetics, 10(8), e1004576. doi:10.1371/journal.pgen.1004576[Full]
402015Dorshorst B, Harun-Or-Rashid M, Bagherpoor A.J, Rubin C, Ashwell C, Gourichon D, Tixier-Boichard M, Hallböök F, Andersson L. (2015) A Genomic Duplication is Associated with Ectopic Eomesodermin Expression in the Embryonic Chicken Comb and Two Duplex-comb Phenotypes. PLoS Genet. 2015 March; 11(3): e1004947.[Full]
412016Bai, H., Sun, Y., Zhu, J., Liu, N., Li, D., Xue, F., … Chen, J. (2016) Study on LOC426217 as a candidate gene for beak deformity in chicken. BMC Genetics, 17, 44.[Full]
422016Zhang, Z., Nie, C., Jia, Y., Jiang, R., Xia, H., Lv, X., … Qu, L. (2016) Parallel Evolution of Polydactyly Traits in Chinese and European Chickens. PLoS ONE, 11(2), e0149010.[Full]
431992Smyth, R., Ponce de Leon, F.A. (1992) Research Note: Linkage Relationship Between the Pea Comb (P) and Extended Black (E) Loci of the Chicken. Poultry Science (1992) 71 (1): 208-210.[Full]
442016Guo Y, Gu X, Sheng Z, et al. (2016) A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens. Leeb T, ed. PLoS Genetics. 2016;12(6):e1006071. doi:10.1371/journal.pgen.1006071.[Full]
452016Jin, S., Zhu, F., Wang, Y., Yi, G., Li, J., Lian, L., … Yang, N. (2016). Deletion of Indian hedgehog gene causes dominant semi-lethal Creeper trait in chicken. Scientific Reports, 2016, 6, 30172.[Full]
462017Schwochow Thalmann, D., Ring, H., Sundström, E., Cao, X., Larsson, M., Kerje, S., … Andersson, L. (2017). The evolution of Sex-linked barring alleles in chickens involves both regulatory and coding changes in CDKN2A. PLoS Genetics, 13(4), e1006665.[Full]
472017He, C., Chen, Y., Yang, K., Zhai, Z., Zhao, W., Liu, S., … Meng, H. (2017). Genetic pattern and gene localization of polydactyly in Beijing fatty chicken. PLoS ONE, 12(5), e0176113.
482014Zheng C, Li Z, Yang N, Ning Z. Quantitative expression of candidate genes affecting eggshell color. Anim Sci J. 2014 May;85(5):506-10. doi: 10.1111/asj.12182. Epub 2014 Mar 10. PMID: 24612318.[abstract]
492021Wu Z, Bortoluzzi C, Derks MFL, Liu L, Bosse M, Hiemstra SJ, Groenen MAM, Crooijmans RPMA. Heterogeneity of a dwarf phenotype in Dutch traditional chicken breeds revealed by genomic analyses. Evol Appl. 2021 Jan 19;14(4):1095-1108. doi: 10.1111/eva.13183. PMID: 33897823; PMCID: PMC8061282.[abstract]