The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries)


Autoři: Alexandra M. Sparks aff001;  Kathryn Watt aff001;  Rona Sinclair aff001;  Jill G. Pilkington aff001;  Josephine M. Pemberton aff001;  Tom N. McNeilly aff003;  Daniel H. Nussey aff001;  Susan E. Johnston aff001
Působiště autorů: Institutes of Evolutionary Biology and Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom aff001;  Faculty of Biological Sciences, School of Biology, University of Leeds, Leeds, United Kingdom aff002;  Moredun Research Institute, Pentlands Science Park, Bush Loan, Midlothian, United Kingdom aff003
Vyšlo v časopise: The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries). PLoS Genet 15(11): e32767. doi:10.1371/journal.pgen.1008461
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008461

Souhrn

Much of our knowledge of the drivers of immune variation, and how these responses vary over time, comes from humans, domesticated livestock or laboratory organisms. While the genetic basis of variation in immune responses have been investigated in these systems, there is a poor understanding of how genetic variation influences immunity in natural, untreated populations living in complex environments. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We assayed IgA, IgE and IgG antibodies against the prevalent nematode Teladorsagia circumcincta in the blood plasma of > 3,000 sheep collected over 26 years. Antibody levels were significantly heritable (h2 = 0.21 to 0.57) and highly stable over an individual’s lifespan. IgA levels were strongly associated with a region on chromosome 24 explaining 21.1% and 24.5% of heritable variation in lambs and adults, respectively. This region was adjacent to two candidate loci, Class II Major Histocompatibility Complex Transactivator (CIITA) and C-Type Lectin Domain Containing 16A (CLEC16A). Lamb IgA levels were also associated with the immunoglobulin heavy constant loci (IGH) complex, and adult IgE levels and lamb IgA and IgG levels were associated with the major histocompatibility complex (MHC). This study provides evidence of high heritability of a complex immunological trait under natural conditions and provides the first evidence from a genome-wide study that large effect genes located outside the MHC region exist for immune traits in the wild.

Klíčová slova:

Antibodies – Genetic loci – Genetic polymorphism – Genome-wide association studies – Major histocompatibility complex – Molecular genetics – Sheep – Genetics of the immune system


Zdroje

1. Pedersen AB, Babayan SA. Wild immunology. Mol Ecol. 2011;20: 872–880. doi: 10.1111/j.1365-294X.2010.04938.x 21324009

2. Maizels RM, Nussey DH. Into the wild: digging at immunology’s evolutionary roots. Nat Immunol. 2013;14: 879–883. doi: 10.1038/ni.2643 23959175

3. Liston A, Carr EJ, Linterman MA. Shaping variation in the human immune system. Trends Immunol. 2016;37: 637–646. doi: 10.1016/j.it.2016.08.002 27692231

4. Orrù V, Steri M, Sole G, Sidore C, Virdis F, Dei M, et al. Genetic variants regulating immune cell levels in health and disease. Cell. 2013;155: 242–256. doi: 10.1016/j.cell.2013.08.041 24074872

5. Roederer M, Quaye L, Mangino M, Beddall MH, Mahnke Y, Chattopadhyay P, et al. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis. Cell. 2015;161: 387–403. doi: 10.1016/j.cell.2015.02.046 25772697

6. Atlija M, Arranz J-J, Martinez-Valladares M, Gutiérrez-Gil B. Detection and replication of QTL underlying resistance to gastrointestinal nematodes in adult sheep using the ovine 50K SNP array. Genet Sel Evol. 2016;48: 4. doi: 10.1186/s12711-016-0182-4 26791855

7. Yang I V, Wade CM, Kang HM, Alper S, Rutledge H, Lackford B, et al. Identification of novel genes that mediate innate immunity using inbred mice. Genetics. 2009;183: 1535–1544. doi: 10.1534/genetics.109.107540 19805818

8. Thompson-Crispi KA, Sewalem A, Miglior F, Mallard BA. Genetic parameters of adaptive immune response traits in Canadian Holsteins. J Dairy Sci. 2012;95: 401–409. doi: 10.3168/jds.2011-4452 22192219

9. Abolins S, King EC, Lazarou L, Weldon L, Hughes L, Drescher P, et al. The comparative immunology of wild and laboratory mice, Mus musculus domesticus. Nat Commun. 2017;8: 14811. doi: 10.1038/ncomms14811 28466840

10. Beura LK, Hamilton SE, Bi K, Schenkel JM, Odumade OA, Casey KA, et al. Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature. 2016;532: 512–516. doi: 10.1038/nature17655 27096360

11. Murphy L, Eckersall PD, Bishop SC, Pettit JJ, Huntley JF, Burchmore R, et al. Genetic variation among lambs in peripheral IgE activity against the larval stages of Teladorsagia circumcincta. Parasitology. 2010;137: 1249–1260. doi: 10.1017/S0031182010000028 20233490

12. Strain SAJ, Bishop SC, Henderson NG, Kerr A, McKellar QA, Mitchell S, et al. The genetic control of IgA activity against Teladorsagia circumcincta and its association with parasite resistance in naturally infected sheep. Parasitology. 2002;124: 545–552. doi: 10.1017/s0031182002001531 12049417

13. Clapperton M, Glass EJ, Bishop SC. Pig peripheral blood mononuclear leucocyte subsets are heritable and genetically correlated with performance. Animal. 2008;2: 1575–1584. doi: 10.1017/S1751731108002929 22444008

14. Flori L, Gao Y, Oswald IP, Lefevre F, Bouffaud M, Mercat M-J, et al. Deciphering the genetic control of innate and adaptive immune responses in pig: a combined genetic and genomic study. BMC Proc. 2011;5: S32. doi: 10.1186/1753-6561-5-S4-S32 21645313

15. Denholm SJ, McNeilly TN, Banos G, Coffey MP, Russell GC, Bagnall A, et al. Estimating genetic and phenotypic parameters of cellular immune-associated traits in dairy cows. J Dairy Sci. 2017;100: 2850–2862. doi: 10.3168/jds.2016-11679 28131586

16. Davies G, Stear MJ, Benothman M, Abuagob O, Kerr A, Mitchell S, et al. Quantitative trait loci associated with parasitic infection in Scottish blackface sheep. Heredity. 2006;96: 252–258. doi: 10.1038/sj.hdy.6800788 16391549

17. Edfors-Lilja I, Wattrang E, Marklund L, Moller M, Andersson-Eklund L, Andersson L, et al. Mapping quantitative trait loci for immune capacity in the pig. J Immunol. 1998;161: 829–835. 9670960

18. Lu X, Liu JF, Fu WX, Zhou JP, Luo YR, Ding XD, et al. Genome-wide association study for cytokines and immunoglobulin G in swine. PLoS One. 2013;8: 1–7. doi: 10.1371/journal.pone.0074846 24098351

19. Thompson-Crispi KA, Sargolzaei M, Ventura R, Abo-Ismail M, Miglior F, Schenkel F, et al. A genome-wide association study of immune response traits in Canadian Holstein cattle. BMC Genomics. 2014;15: 559. doi: 10.1186/1471-2164-15-559 24996426

20. Pitala N, Gustafsson L, Sendecka J, Brommer JE. Nestling immune response to phytohaemagglutinin is not heritable in collared flycatchers. Biol Lett. 2007;3: 418–421. doi: 10.1098/rsbl.2007.0135 17567550

21. Morrison ES, Ardia DR, Clotfelter ED. Cross-fostering reveals sources of variation in innate immunity and hematocrit in nestling tree swallows Tachycineta bicolor. J Avian Biol. 2009;40: 573–578. doi: 10.1111/j.1600-048X.2009.04910.x

22. Sakaluk SK, Wilson AJ, Bowers EK, Johnson LS, Masters BS, Johnson BG, et al. Genetic and environmental variation in condition, cutaneous immunity, and haematocrit in house wrens. BMC Evol Biol. 2014;14: 242. doi: 10.1186/s12862-014-0242-8 25471117

23. Kim S-Y, Fargallo JA, Vergara P, Martínez-Padilla J. Multivariate heredity of melanin-based coloration, body mass and immunity. Heredity. 2013;111: 139–146. doi: 10.1038/hdy.2013.29 23591519

24. Drobniak SM, Wiejaczka D, Arct A, Dubiec A, Gustafsson L, Cichoń M. Sex-specific heritability of cell-mediated immune response in the blue tit nestlings (Cyanistes caeruleus). J Evol Biol. 2010;23: 1286–1292. doi: 10.1111/j.1420-9101.2010.01993.x 20456564

25. Bonneaud C, Sinsheimer JS, Richard M, Chastel O, Sorci G. MHC polymorphisms fail to explain the heritability of phytohaemagglutinin-induced skin swelling in a wild passerine. Biol Lett. 2009;5: 784–787. doi: 10.1098/rsbl.2009.0435 19671600

26. Coltman DW, Wilson K, Pilkington JG, Stear MJ, Pemberton JM. A microsatellite polymorphism in the gamma interferon gene is associated with resistance to gastrointestinal nematodes in a naturally-parasitized population of Soay sheep. Parasitology. 2001;122: 571–582. doi: 10.1017/s0031182001007570 11393831

27. Turner AK, Begon M, Jackson JA, Bradley JE, Paterson S. Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population. PLoS Genet. 2011;7: e1002343. doi: 10.1371/journal.pgen.1002343 22039363

28. Brown EA, Pilkington JG, Nussey DH, Watt KA, Hayward AD, Tucker R, et al. Detecting genes for variation in parasite burden and immunological traits in a wild population: testing the candidate gene approach. Mol Ecol. 2013;22: 757–773. doi: 10.1111/j.1365-294X.2012.05757.x 22998224

29. Wenzel MA, James MC, Douglas A, Piertney SB. Genome-wide association and genome partitioning reveal novel genomic regions underlying variation in gastrointestinal nematode burden in a wild bird. Mol Ecol. 2015;24: 4175–4192. doi: 10.1111/mec.13313 26179597

30. Paterson S, Wilson K, Pemberton JM. Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.). Proc Natl Acad Sci U S A. 1998;95: 3714–3719. doi: 10.1073/pnas.95.7.3714 9520432

31. Kennedy MW, Nager RG. The perils and prospects of using phytohaemagglutinin in evolutionary ecology. Trends Ecol Evol. 2006;21: 653–655. doi: 10.1016/j.tree.2006.09.017 17028055

32. Owen JP, Clayton DH. Where are the parasites in the PHA response? Trends Ecol Evol. 2007;22: 228–229. doi: 10.1016/j.tree.2007.02.003 17296246

33. Schmid-Hempel P. Evolutionary Parasitology: The Integrated Study of Infections, Immunology, Ecology, and Genetics. New York: Oxford University Press; 2011.

34. Jepson A, Banya W, Sisay-Joof F, Hassan-King M, Nunes C, Bennett S, et al. Quantification of the relative contribution of major histocompatibility complex (MHC) and non-MHC genes to human immune responses to foreign antigens. Infect Immun. 1997;65: 872–876. 9038290

35. Acevedo-Whitehouse K, Cunningham AA. Is MHC enough for understanding wildlife immunogenetics? Trends Ecol Evol. 2006;21: 433–438. doi: 10.1016/j.tree.2006.05.010 16764966

36. Palacios MG, Winkler DW, Klasing KC, Hasselquist D, Vleck CM. Consequences of immune system aging in nature: a study of immunosenescence costs in free-living Tree Swallows. Ecology. 2011;92: 952–966. doi: 10.1890/10-0662.1 21661557

37. Simon AK, Hollander GA, McMichael A. Evolution of the immune system in humans from infancy to old age. Proceedings Biol Sci. 2015;282: 20143085. doi: 10.1098/rspb.2014.3085 26702035

38. Tsang JS, Schwartzberg PL, Kotliarov Y, Biancotto A, Xie Z, Germain RN, et al. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell. 2014;157: 499–513. doi: 10.1016/j.cell.2014.03.031 24725414

39. Carr EJ, Dooley J, Garcia-Perez JE, Lagou V, Lee JC, Wouters C, et al. The cellular composition of the human immune system is shaped by age and cohabitation. Nat Immunol. 2016;17: 461–468. doi: 10.1038/ni.3371 26878114

40. Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJL, Furman D, et al. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015;160: 37–47. doi: 10.1016/j.cell.2014.12.020 25594173

41. Banos G, Wall E, Coffey MP, Bagnall A, Gillespie S, Russell GC, et al. Identification of immune traits correlated with dairy cow health, reproduction and productivity. PLoS One. 2013;8: e65766. doi: 10.1371/journal.pone.0065766 23776543

42. Benavides MV, Sonstegard TS, Van Tassell C. Genomic regions associated with sheep resistance to gastrointestinal nematodes. Trends Parasitol. 2016;32: 470–480. doi: 10.1016/j.pt.2016.03.007 27183838

43. McNeilly TN, Devaney E, Matthews JB. Teladorsagia circumcincta in the sheep abomasum: defining the role of dendritic cells in T cell regulation and protective immunity. Parasite Immunol. 2009;31: 347–356. doi: 10.1111/j.1365-3024.2009.01110.x 19527450

44. Stear MJ, Bishop SC, Doligalska M, Duncan JL, Holmes PH, Irvine J, et al. Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta. Parasite Immunol. 1995;17: 643–652. doi: 10.1111/j.1365-3024.1995.tb01010.x 8834764

45. Riggio V, Matika O, Pong-Wong R, Stear MJ, Bishop SC. Genome-wide association and regional heritability mapping to identify loci underlying variation in nematode resistance and body weight in Scottish Blackface lambs. Heredity. 2013;110: 420–429. doi: 10.1038/hdy.2012.90 23512009

46. Gutiérrez-Gil B, Pérez J, de la Fuente LF, Meana A, Martínez-Valladares M, San Primitivo F, et al. Genetic parameters for resistance to trichostrongylid infection in dairy sheep. Animal. 2010;4: 505–512. doi: 10.1017/S1751731109991431 22444037

47. Bishop SC, Stear MJ. Inheritance of faecal egg counts during early lactation in Scottish Blackface ewes facing mixed, natural nematode infections. Anim Sci. 2001;73: 389–395. doi: 10.1017/S1357729800058355

48. Gutiérrez-Gil B, Pérez J, Alvarez L, Martínez-Valladares M, de la Fuente L-F, Bayón Y, et al. Quantitative trait loci for resistance to trichostrongylid infection in Spanish Churra sheep. Genet Sel Evol. 2009;41: 46. doi: 10.1186/1297-9686-41-46 19863786

49. Nieuwhof GJ, Bishop SC. Costs of the major endemic diseases of sheep in Great Britain and the potential benefits of reduction in disease impact. Anim Sci. 2005;81: 23–29. doi: 10.1079/ASC41010023

50. Kaplan RM, Vidyashankar AN. An inconvenient truth: global worming and anthelmintic resistance. Vet Parasitol. 2012;186: 70–78. doi: 10.1016/j.vetpar.2011.11.048 22154968

51. Jackson F, Miller J. Alternative approaches to control—quo vadit? Vet Parasitol. 2006;139: 371–384. doi: 10.1016/j.vetpar.2006.04.025 16750600

52. De Cisneros JPJ, Stear MJ, Mair C, Singleton D, Stefan T, Stear A, et al. An explicit immunogenetic model of gastrointestinal nematode infection in sheep. J R Soc Interface. 2014;11. doi: 10.1098/rsif.2014.0416 25121649

53. Wilson K, Grenfell BT, Pilkington JG, Boyd HEG, Gulland FM. Parasites and their impact. In: Clutton-Brock TH, Pemberton JM, editors. Soay Sheep: Dynamics and Selection in an Island Population. Cambridge, UK: Cambridge University Press; 2004. pp. 17–51.

54. Craig BH, Pilkington JG, Pemberton JM. Gastrointestinal nematode species burdens and host mortality in a feral sheep population. Parasitology. 2006;133: 485–496. doi: 10.1017/S0031182006000618 16817995

55. Gulland FM. The role of nematode parasites in Soay sheep (Ovis aries L.) mortality during a population crash. Parasitology. 1992;105: 493–503. doi: 10.1017/s0031182000074679 1461688

56. Hayward AD, Wilson AJ, Pilkington JG, Clutton-Brock TH, Pemberton JM, Kruuk LEB. Natural selection on a measure of parasite resistance varies across ages and environmental conditions in a wild mammal. J Evol Biol. 2011;24: 1664–1676. doi: 10.1111/j.1420-9101.2011.02300.x 21658142

57. Hayward AD, Garnier R, Watt KA, Pilkington JG, Grenfell BT, Matthews JB, et al. Heritable, heterogeneous, and costly resistance of sheep against nematodes and potential feedbacks to epidemiological dynamics. Am Nat. 2014;184: S58–76. doi: 10.1086/676929 25061678

58. Nussey DH, Watt KA, Clark A, Pilkington JG, Pemberton JM, Graham AL, et al. Multivariate immune defences and fitness in the wild: complex but ecologically important associations among plasma antibodies, health and survival. Proc R Soc London B Biol Sci. 2014;281: 20132931. doi: 10.1098/rspb.2013.2931 24500168

59. Watson RL, McNeilly TN, Watt KA, Pemberton JM, Pilkington JG, Waterfall M, et al. Cellular and humoral immunity in a wild mammal: variation with age & sex and association with overwinter survival. Ecol Evol. 2016;6: 8695–8705. doi: 10.1002/ece3.2584 28035261

60. Sparks AM, Watt K, Sinclair R, Pilkington JG, Pemberton JM, Johnston SE, et al. Natural Selection on Antihelminth Antibodies in a Wild Mammal Population. Am Nat. 2018;192: 745–760. doi: 10.1086/700115 30444657

61. Beraldi D, McRae AF, Gratten J, Pilkington JG, Slate J, Visscher PM, et al. Quantitative trait loci (QTL) mapping of resistance to strongyles and coccidia in the free-living Soay sheep (Ovis aries). Int J Parasitol. 2007;37: 121–129. doi: 10.1016/j.ijpara.2006.09.007 17067607

62. Johnston SE, Gratten J, Berenos C, Pilkington JG, Clutton-Brock TH, Pemberton JM, et al. Life history trade-offs at a single locus maintain sexually selected genetic variation. Nature. 2013;502: 93–95. doi: 10.1038/nature12489 23965625

63. Bérénos C, Ellis PA, Pilkington JG, Lee SH, Gratten J, Pemberton JM. Heterogeneity of genetic architecture of body size traits in a free-living population. Mol Ecol. 2015;24: 1810–1830. doi: 10.1111/mec.13146 25753777

64. Johnston SE, Bérénos C, Slate J, Pemberton JM. Conserved genetic architecture underlying individual recombination rate variation in a wild population of soay sheep (Ovis aries). Genetics. 2016;203: 583–598. doi: 10.1534/genetics.115.185553 27029733

65. Reith W, LeibundGut-Landmann S, Waldburger J-M. Regulation of MHC class II gene expression by the class II transactivator. Nat Rev Immunol. 2005;5: 793–806. doi: 10.1038/nri1708 16200082

66. Krawczyk M, Reith W. Regulation of MHC class II expression, a unique regulatory system identified by the study of a primary immunodeficiency disease. Tissue Antigens. 2006;67: 183–197. doi: 10.1111/j.1399-0039.2006.00557.x 16573555

67. Ferreira RC, Pan-Hammarström Q, Graham RR, Gateva V, Fontán G, Lee AT, et al. Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. Nat Genet. 2010;42: 777–780. doi: 10.1038/ng.644 20694011

68. Li J, Jørgensen SF, Maggadottir SM, Bakay M, Warnatz K, Glessner J, et al. Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells. Nat Commun. 2015;6: 6804. doi: 10.1038/ncomms7804 25891430

69. Bronson PG, Chang D, Bhangale T, Seldin MF, Ortmann W, Ferreira RC, et al. Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency. Nat Genet. 2016;48: 1425–1429. doi: 10.1038/ng.3675 27723758

70. Liu W, Yan M, Liu Y, Wang R, Li C, Deng C, et al. Olfactomedin 4 down-regulates innate immunity against Helicobacter pylori infection. Proc Natl Acad Sci U S A. 2010;107: 11056–11061. doi: 10.1073/pnas.1001269107 20534456

71. Chaplin JW, Kasahara S, Clark EA, Ledbetter JA. Anti-CD180 (RP105) Activates B Cells To Rapidly Produce Polyclonal Ig via a T Cell and MyD88-Independent Pathway. J Immunol. 2011;187: 4199–4209. doi: 10.4049/jimmunol.1100198 21918197

72. Coulson T, Catchpole EA, Albon SD, Morgan BJT, Pemberton JM, Clutton-Brock TH, et al. Age, sex, density, winter weather and population crashes in Soay sheep. Science. 2001;292: 1528–1531. doi: 10.1126/science.292.5521.1528 11375487

73. Crawley MJ, Albon SD, Bazely DR, Milner JM, Pilkington JG, Tuke AL. Vegetation and sheep population dynamics. In: Clutton-Brock TH, Pemberton JM, editors. Soay Sheep: Dynamics and Selection in an Island Population. Cambridge: Cambridge University Press; 2004. pp. 89–112.

74. Falconer DS, Mackay TFC. Introduction to Quantitative Genetics. 4th ed. UK: Longman; 1996.

75. Seppälä O. Natural selection on quantitative immune defence traits: a comparison between theory and data. J Evol Biol. 2015;28: 1–9. doi: 10.1111/jeb.12528 25400248

76. Mori-Aoki A, Pietrarelli M, Nakazato M, Caturegli P, Kohn LD, Suzuki K. Class II Transactivator Suppresses Transcription of Thyroid-Specific Genes. Biochem Biophys Res Commun. 2000;278: 58–62. doi: 10.1006/bbrc.2000.3769 11071855

77. Chang C-H, Guerder S, Hong S-C, van Ewijk W, Flavell RA. Mice Lacking the MHC Class II Transactivator (CIITA) Show Tissue-Specific Impairment of MHC Class II Expression. Immunity. 1996;4: 167–178. doi: 10.1016/s1074-7613(00)80681-0 8624807

78. DeSandro AM, Nagarajan UM, Boss JM. Associations and interactions between bare lymphocyte syndrome factors. Mol Cell Biol. 2000;20: 6587–6599. doi: 10.1128/mcb.20.17.6587-6599.2000 10938133

79. Sawcer S, Hellenthal G, Pirinen M, Spencer CCA, Patsopoulos NA, Moutsianas L, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476: 214–219. doi: 10.1038/nature10251 21833088

80. Leikfoss IS, Keshari PK, Gustavsen MW, Bjolgerud A, Brorson IS, Celius EG, et al. Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells. PLoS One. 2015;10: e0132957. doi: 10.1371/journal.pone.0132957 26203907

81. Wang Y, Yuan W, Guo H, Jiang Y. High frequency of activated NKp46(+) natural killer cells in patients with new diagnosed of latent autoimmune diabetes in adults. Autoimmunity. 2015;48: 267–273. doi: 10.3109/08916934.2014.990629 25495606

82. Márquez A, Varadé J, Robledo G, Martínez A, Mendoza JL, Taxonera C, et al. Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15- Crohn’s disease patients. Eur J Hum Genet. 2009;17: 1304–1308. doi: 10.1038/ejhg.2009.50 19337309

83. Skinningsrud B, Husebye ES, Pearce SH, McDonald DO, Brandal K, Wolff AB, et al. Polymorphisms in CLEC16A and CIITA at 16p13 Are Associated with Primary Adrenal Insufficiency. J Clin Endocrinol Metab. 2008;93: 3310–3317. doi: 10.1210/jc.2008-0821 18593762

84. Skinningsrud B, Lie BA, Husebye ES, Kvien TK, Førre Ø, Flatø B, et al. A CLEC16A variant confers risk for juvenile idiopathic arthritis and anti-cyclic citrullinated peptide antibody negative rheumatoid arthritis. Ann Rheum Dis. 2010;69: 1471–1474. doi: 10.1136/ard.2009.114934 19734133

85. Pandey R, Bakay M, Hain HS, Strenkowski B, Elsaqa BZB, Roizen JD, et al. CLEC16A regulates splenocyte and NK cell function in part through MEK signaling. PLoS One. 2018;13: e0203952. Available: doi: 10.1371/journal.pone.0203952 30226884

86. Graham AL, Hayward AD, Watt KA, Pilkington JG, Pemberton JM, Nussey DH. Fitness correlates of heritable variation in antibody responsiveness in a wild mammal. Science. 2010;330: 662–665. doi: 10.1126/science.1194878 21030656

87. Diao Y, Fang R, Li B, Meng Z, Yu J, Qiu Y, et al. A tiling-deletion-based genetic screen for cis-regulatory element identification in mammalian cells. Nat Methods. 2017;14: 629–635. doi: 10.1038/nmeth.4264 28417999

88. Orsolya S, François S. From remote enhancers to gene regulation: charting the genome’s regulatory landscapes. Philos Trans R Soc B Biol Sci. 2013;368: 20120358. doi: 10.1098/rstb.2012.0358 23650632

89. Crawford AM, Paterson KA, Dodds KG, Diez Tascon C, Williamson PA, Roberts Thomson M, et al. Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees. BMC Genomics. 2006;7: 178. doi: 10.1186/1471-2164-7-178 16846521

90. Kijas JW, Lenstra JA, Hayes B, Boitard S, Porto Neto LR, San Cristobal M, et al. Genome-wide analysis of the world’s sheep breeds reveals high levels of historic mixture and strong recent selection. PLoS Biol. 2012;10: e1001258. doi: 10.1371/journal.pbio.1001258 22346734

91. Feulner PGD, Gratten J, Kijas JW, Visscher PM, Pemberton JM, Slate J. Introgression and the fate of domesticated genes in a wild mammal population. Mol Ecol. 2013;22: 4210–4221. doi: 10.1111/mec.12378 23786437

92. Husby A, Kawakami T, Ronnegard L, Smeds L, Ellegren H, Qvarnstrom A. Genome-wide association mapping in a wild avian population identifies a link between genetic and phenotypic variation in a life-history trait. Proc R Soc London B Biol Sci. 2015;282: 20150156. doi: 10.1098/rspb.2015.0156 25833857

93. Johnston SE, Orell P, Pritchard VL, Kent MP, Lien S, Niemelä E, et al. Genome-wide SNP analysis reveals a genetic basis for sea-age variation in a wild population of Atlantic salmon (Salmo salar). Mol Ecol. 2014;23: 3452–3468. doi: 10.1111/mec.12832 24931807

94. Kardos M, Husby A, McFarlane SE, Qvarnström A, Ellegren H. Whole-genome resequencing of extreme phenotypes in collared flycatchers highlights the difficulty of detecting quantitative trait loci in natural populations. Mol Ecol Resour. 2016;16: 727–741. doi: 10.1111/1755-0998.12498 26649993

95. Santure AW, Poissant J, De Cauwer I, Van Oers K, Robinson MR, Quinn JL, et al. Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations. Mol Ecol. 2015;24: 6148–6162. doi: 10.1111/mec.13452 26661500

96. Silva CNS, McFarlane SE, Hagen IJ, Rönnegård L, Billing AM, Kvalnes T, et al. Insights into the genetic architecture of morphological traits in two passerine bird species. Heredity. 2017;119: 197–205. doi: 10.1038/hdy.2017.29 28613280

97. Santure AW, Garant D. Wild GWAS—association mapping in natural populations. Mol Ecol Resour. 2018;18: 729–738. doi: 10.1111/1755-0998.12901 29782705

98. Bérénos C, Ellis P, Pilkington JG, Pemberton JM. Estimating quantitative genetic parameters in wild populations: a comparison of pedigree and genomic approaches. Mol Ecol. 2014;23: 3434–3451. doi: 10.1111/mec.12827 24917482

99. Clutton-Brock T, Pemberton J. Soay sheep: dynamics and selection in an island population. Cambridge, UK: Cambridge University Press; 2004.

100. Aulchenko YS, Ripke S, Isaacs A, van Duijn CM. GenABEL: an R library for genome-wide association analysis. Bioinformatics. 2007;23: 1294–1296. doi: 10.1093/bioinformatics/btm108 17384015

101. Jiang Y, Xie M, Chen W, Talbot R, Maddox JF, Faraut T, et al. The sheep genome illuminates biology of the rumen and lipid metabolism. Science. 2014;344: 1168–1173. doi: 10.1126/science.1252806 24904168

102. Huisman J. Pedigree reconstruction from SNP data: parentage assignment, sibship clustering and beyond. Mol Ecol Resour. 2017;17: 1009–1024. doi: 10.1111/1755-0998.12665 28271620

103. Henderson CR. Best linear unbiased estimation and prediction under a selection model. Biometrics. 1975;31: 423–447. doi: 10.2307/2529430 1174616

104. Butler DG, Cullis BR, Gilmour AR, Gogel BJ. Mixed Models for S language Environments: ASReml-R reference manual. 2009.

105. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet. 2011;88: 76–82. doi: 10.1016/j.ajhg.2010.11.011 21167468

106. Devlin AB, Roeder K, Devlin B. Genomic Control for Association. Biometrics. 1999;55: 997–1004. 11315092

107. Moskvina V, Schmidt KM. On multiple-testing correction in genome-wide association studies. Genet Epidemiol. 2008;32: 567–573. doi: 10.1002/gepi.20331 18425821

108. Nagamine Y, Pong-Wong R, Navarro P, Vitart V, Hayward C, Rudan I, et al. Localising Loci underlying Complex Trait Variation Using Regional Genomic Relationship Mapping. PLoS One. 2012;7: e46501. doi: 10.1371/journal.pone.0046501 23077511

109. Hickey JM, Kinghorn BP, Tier B, Werf JHJ Van Der, Cleveland MA. A phasing and imputation method for pedigreed populations that results in a single-stage genomic evaluation. Genet Sel Evol. 2012;44: 9. doi: 10.1186/1297-9686-44-9 22462519

110. Durinck S, Spellman PT, Birney E, Huber W. Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat Protoc. 2009;4: 1184–1191. doi: 10.1038/nprot.2009.97 19617889

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Genetika Reprodukční medicína

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PLOS Genetics


2019 Číslo 11

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