Identification of QTLs for behavioral reactivity to social separation and humans in sheep using the OvineSNP50 BeadChip

BMC Genomics

Alain Boissy³  Guillaume Sallé¹  Jacques Bouix¹  Dominique François¹  Eric Delval³  Didier Foulquié²  Carole Moreno¹  Dominique Hazard¹ 

[1] Université de Toulouse INPT ENVT, UMR1388 Génétique, Physiologie et Systèmes d’Elevage, F-31076 Toulouse, France;INRA UE321 La Fage, Saint Jean et Saint Paul, F-12250 Roquefort-sur-Soulzon, France;Université de Lyon, VetAgro Sup, UMR1213 Herbivores, F-69280 Marcy l’Etoile, France

关键词: Cortisol;    Human;    Gregariousness;    Quantitative trait loci;    Behavioral reactivity;    Sheep;   

Others  :  1140653
DOI  :  10.1186/1471-2164-15-778

 received in 2014-04-25, accepted in 2014-09-04,  发布年份 2014

【 摘 要 】

Background

Current trends in sheep farming practices rely on animals with a greater level of behavioral autonomy than before, a phenotype that actively contributes to the sustainability of animal production. Social reactivity and reactivity to humans are relevant behavioral traits in sheep, known for their strong gregariousness and weak tolerance to handling, which have previously been reported with moderate to high heritabilities. To identify loci underlying such behaviors, we performed a genome study in Romane lambs.

Results

The experiment was carried out on 934 male and female lambs allocated into 9 half-sib families (average of 103 lambs per family) and reared outside. After weaning, all the lambs were individually exposed to 4 standardized behavioral tests combining social isolation, exposure to humans or handling, confinement and novelty (i.e. arena test, corridor test, isolation box test, shearing test). A broad range of behaviors including vocalizations, locomotion, vigilance and flight distance, as well as the cortisol response to handling, were collected. All lambs were genotyped using the Illumina OvineSNP50 BeadChip. QTL detection was performed by linkage, association and joint linkage and association analyses using the QTLmap software. Five main QTL regions were identified on sheep chromosomes (Ovis Aries Region, OAR) 12, 16, 19, 21 and 23 among many other QTLs with small to moderate effects. The QTLs on OAR12, 16 and 21 showed significant associations with social reactivity. The QTLs on OAR19 and 23 were found to be associated with reactivity to humans. No overlapping QTLs were identified for the different traits measured in the behavioral tests, supporting the hypothesis that different genetic factors influence social reactivity and tolerance to humans.

Conclusion

The results of this study using ovine SNP data suggest that in domestic sheep the behavioral responses to social separation and exposure to humans are under polygenic influence. The most relevant QTLs reported in the present study contain interesting candidate genes previously described to be associated with various emotional and social behaviors in mammals.

【 授权许可】

   
2014 Hazard et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Boissy A, Fisher AD, Bouix J, Hinch GN, Le Neindre P: Genetics of fear in ruminant livestock. Livest Prod Sci 2005, 93(1):23-32.
• [2]Mason GJ, Cooper J, Clarebrough C: Frustrations of fur-farmed mink. Nature 2001, 410(6824):35-36.
• [3]Dantzer R, Mormede P: Stress in farm animals - a need for reevaluation. J Anim Sci 1983, 57(1):6-18.
• [4]Koolhaas JM, de Boer SF, Bohus B: Motivational systems or motivational states: behavioural and physiological evidence. Appl Anim Behav Sci 1997, 53(1):131-143.
• [5]Koolhaas JM, Korte SM, De Boer SF, Van Der Vegt BJ, Van Reenen CG, Hopster H, De Jong IC, Ruis MAW, Blokhuis HJ: Coping styles in animals: current status in behavior and stress-physiology. Neurosci Biobehav Rev 1999, 23(7):925-935.
• [6]Rauw WM, Kanis E, Noordhuizen-Stassen EN, Grommers FJ: Undesirable side effects of selection for high production efficiency in farm animals: a review. Livest Prod Sci 1998, 56(1):15-33.
• [7]Rauw WM: Physiological consequences of selection for increased performance. In Proceedings of the Seventeenth Conference of the Association for the Advancement of Animal Breeding and Genetics: 23–26 September 2007; Armidale. Australia: Association for the Advancement of Animal Breeding and Genetics; 2007:240-247.
• [8]Cockram MS: A review of behavioural and physiological responses of sheep to stressors to identify potential behavioural signs of distress. Anim Welf 2004, 13(3):283-291.
• [9]Recoquillay J, Leterrier C, Calandreau L, Bertin A, Pitel F, Gourichon D, Vignal A, Beaumont C, Le Bihan-Duval E, Arnould C: Evidence of phenotypic and genetic relationships between sociality, emotional reactivity and production traits in Japanese Quail. Plos One 2013, 8(12):e82157.
• [10]Porter RH, Nowak R, Orgeur P: Influence of a conspecific agemate on distress bleating by lambs. Appl Anim Behav Sci 1995, 45(3–4):239-244.
• [11]Estevez I, Andersen I-L, Nævdal E: Group size, density and social dynamics in farm animals. Appl Anim Behav Sci 2007, 103(3):185-204.
• [12]Visscher PM, Goddard ME: Genetic Parameters for milk yield, survival, workability, and type traits for australian dairy cattle. J Dairy Sci 1995, 78(1):205-220.
• [13]Burrow HM: Variances and covariances between productive and adaptive traits and temperament in a composite breed of tropical beef cattle. Livest Prod Sci 2001, 70(3):213-233.
• [14]Kilgour RJ: Arena behaviour is a possible selection criterion for lamb-rearing ability; it can be measured in young rams and ewes. Appl Anim Behav Sci 1998, 57(1):81-89.
• [15]Hemsworth PH: Human-animal interactions in livestock production. Appl Anim Behav Sci 2003, 81(3):185-198.
• [16]Rushen J, Taylor AA, de Passillé AM: Domestic animals’ fear of humans and its effect on their welfare. Appl Anim Behav Sci 1999, 65(3):285-303.
• [17]Boissy A, Nowak R, Orgeur P, Veissier I: Social relationships in domestic ruminants: constraints and means for the integration of the animal into its environment. INRA Productions Animales 2001, 14(2):79-90.
• [18]Mignon-Grasteau S, Boissy A, Bouix J, Faure J-M, Fisher AD, Hinch GN, Jensen P, Le Neindre P, Mormède P, Prunet P, Vandeputte M, Beaumont C: Genetics of adaptation and domestication in livestock. Livest Prod Sci 2005, 93(1):3-14.
• [19]Flint J: Analysis of quantitative trait loci that influence animal behavior. J Neurobiol 2003, 54(1):46-77.
• [20]O’Connell LA, Hofmann HA: Genes, hormones, and circuits: an integrative approach to study the evolution of social behavior. Front Neuroendocrinol 2011, 32(3):320-335.
• [21]Robinson GE, Fernald RD, Clayton DF: Genes and social behavior. Science 2008, 322(5903):896-900.
• [22]Donaldson ZR, Young LJ: Oxytocin, vasopressin, and the neurogenetics of sociality. Science 2008, 322(5903):900-904.
• [23]Romeyer A, Bouissou MF: Assessment of fear reactions in domestic sheep, and influence of breed and rearing conditions. Appl Anim Behav Sci 1992, 34(1–2):93-119.
• [24]Vandenheede M, Bouissou MF, Picard M: Interpretation of behavioural reactions of sheep towards fear-eliciting situations. Appl Anim Behav Sci 1998, 58:293-310.
• [25]Boissy A, Bouix J, Orgeur P, Poindron P, Bibe B, Le Neindre P: Genetic analysis of emotional reactivity in sheep: effects of the genotypes of the lambs and of their dams. Genet Sel Evol 2005, 37(4):381-401. BioMed Central Full Text
• [26]Forkman B, Boissy A, Meunier-Salauen MC, Canali E, Jones RB: A critical review of fear tests used on cattle, pigs, sheep, poultry and horses. Physiol Behav 2007, 92(3):340-374.
• [27]McBride SD, Wolf B: Using multivariate statistical analysis to measure ovine temperament; stability of factor construction over time and between groups of animals. Appl Anim Behav Sci 2007, 103(1):45-58.
• [28]Ligout S, Foulquie D, Sebe F, Bouix J, Boissy A: Assessment of sociability in farm animals: the use of arena test in lambs. Appl Anim Behav Sci 2011, 135(1–2):57-62.
• [29]Kilgour RJ, Szantar-Coddington MR: The arena test and cortisol response of sheep as indirect selection criteria for the improvement of lamb survival. Anim Reprod Sci 1997, 46(1):97-108.
• [30]Beausoleil NJ, Blache D, Stafford KJ, Mellor DJ, Noble ADL: Exploring the basis of divergent selection for ‘temperament’ in domestic sheep. Appl Anim Behav Sci 2008, 109(2):261-274.
• [31]Beausoleil NJ, Blache D, Stafford KJ, Mellor DJ, Noble ADL: Selection for temperament in sheep: domain-general and context-specific traits. Appl Anim Behav Sci 2012, 139(1):74-85.
• [32]Le Neindre P, Poindron P, Trillat G, Orgeur P: Influence of breed on reactivity of sheep to humans. Genet Sel Evol 1993, 25(5):447-458. BioMed Central Full Text
• [33]Goddard PJ, Fawcett AR, Macdonald AJ, Reid HW: The behavioural, physiological and immunological responses of lambs from two rearing systems and two genotypes to exposure to humans. Appl Anim Behav Sci 2000, 66(4):305-321.
• [34]Viérin M, Bouissou M-F: Responses of weaned lambs to fear-eliciting situations: origin of individual differences. Dev Psychobiol 2003, 42(2):131-147.
• [35]Wolf BT, McBride SD, Lewis RM, Davies MH, Haresign W: Estimates of the genetic parameters and repeatability of behavioural traits of sheep in an arena test. Appl Anim Behav Sci 2008, 112(1):68-80.
• [36]Morris CA, Cullen NG, Kilgour R, Bremner KJ: Some genetic factors affecting temperament in Bos-Taurus cattle. N Z J Agric Res 1994, 37(2):167-175.
• [37]Canario L, Mignon-Grasteau S, Dupont-Nivet M, Phocas F: Genetics of behavioural adaptation of livestock to farming conditions. Animal 2013, 7(3):357-377.
• [38]Wright D, Nakamichi R, Krause J, Butlin RK: QTL analysis of behavioral and morphological differentiation between wild and laboratory zebrafish (Danio rerio). Behav Genet 2006, 36(2):271-284.
• [39]Wiren A, Jensen P: A growth QTL on chicken chromosome 1 affects emotionality and sociality. Behav Genet 2011, 41(2):303-311.
• [40]Schmutz SM, Stookey JM, Winkelman-Sim DC, Waltz CS, Plante Y, Buchanan FC: A QTL study of cattle behavioral traits in embryo transfer families. J Hered 2001, 92(3):290-292.
• [41]Gutiérrez-Gil B, Ball N, Burton D, Haskell M, Williams JL, Wiener P: Identification of quantitative trait loci affecting cattle temperament. J Hered 2008, 99(6):629-638.
• [42]Mulsant P, Lecerf F, Fabre S, Schibler L, Monget P, Lanneluc I, Pisselet C, Riquet J, Monniaux D, Callebaut I, Cribiu E, Thimonier J, Teyssier J, Bodin L, Cognie Y, Chitour N, Elsen JM: Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. Proc Natl Acad Sci U S A 2001, 98(9):5104-5109.
• [43]Clop A, Marcq F, Takeda H, Pirottin D, Tordoir X, Bibe B, Bouix J, Caiment F, Elsen JM, Eychenne F, Larzul C, Laville E, Meish F, Milenkovic D, Tobin J, Charlier C, Georges M: A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 2006, 38(7):813-818.
• [44]Salle G, Jacquiet P, Gruner L, Cortet J, Sauve C, Prevot F, Grisez C, Bergeaud JP, Schibler L, Tircazes A, Francois D, Pery C, Bouvier F, Thouly JC, Brunel JC, Legarra A, Elsen JM, Bouix J, Rupp R, Moreno CR: A genome scan for QTL affecting resistance to Haemonchus contortus in sheep. J Anim Sci 2012, 90(13):4690-4705.
• [45]Ibeagha-Awemu EM, Kgwatalala P, Zhao X: A critical analysis of production-associated DNA polymorphisms in the genes of cattle, goat, sheep, and pig. Mamm Genome 2008, 19(9):591-617.
• [46]Ricordeau G, Tchamitchian L, Brunel J, Nguyen T, François D: La race ovine INRA 401: un exemple de souche synthétique. INRA Productions Animales 1992, 255-262. Hors série
• [47]Gonzalez-Garcia E, de Figuereido VG, Foulquie D, Jousserand E, Autran P, Camous S, Tesniere A, Bocquier F, Jouven M: Circannual body reserve dynamics and metabolic profile changes in Romane ewes grazing on rangelands. Domest Anim Endocrinol 2014, 46:37-48.
• [48]Murphy P, Purvis I, Lindsay D, Le Neindre P, Orgeur P, Poindron P: Measures of temperament are highly repeatable in Merino sheep and some are related to maternal behaviour. Proc Aust Soc Anim Prod 1994, 20:247-254.
• [49]Boissy A, Bouissou MF: Effects of androgen treatment on behavioural and physiological-responses of heifers to fear-eliciting situations. Horm Behav 1994, 28(1):66-83.
• [50]Elsen JM, Mangin B, Goffinet B, Boichard D, Le Roy P: Alternative models for QTL detection in livestock -1 general introduction. Genet Sel Evol 1999, 31:213-224. BioMed Central Full Text
• [51]Churchill GA, Doerge RW: Empirical threshold values for quantitative trait mapping. Genetics 1994, 138(3):963-971.
• [52]Knott SA, Marklund L, Haley CS, Andersson K, Davies W, Ellegren H, Fredholm M, Hansson I, Hoyheim B, Lundström K, Moller M, Andersson L: Multiple marker mapping of quantitative trait loci in a cross between outbred wild boar and large white pigs. Genetics 1998, 149(2):1069-1080.
• [53]Lynch M, Walsh B: Genetics and Analysis of Quantitative Traits. Sunderland, Massachussets: Sinauer Associates; 1998.
• [54]Meuwissen THE, Goddard ME: Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci. Genetics 2000, 155:421-430.
• [55]Legarra A, Fernando RL: Linear models for joint association and linkage QTL mapping. Genet Sel Evol 2009, 41:43. BioMed Central Full Text
• [56]Piepho HP: A quick method for computing approximate thresholds for quantitative trait loci detection. Genetics 2001, 157(1):425-432.
• [57]Benjamini Y, Hochberg Y: Controlling the false discovery rate - A pratical and powerful approach to multiple testing. J R Stat Soc Ser B-Methodol 1995, 57(1):289-300.
• [58]Matheson SM, Bünger L, Dwyer CM: Genetic parameters for fitness and neonatal behavior traits in sheep. Behav Genet 2012, 42(6):899-911.
• [59]von Borell E, Veissier I: Special section - stress and welfare in farm animals. Physiol Behav 2007, 92(3):291-292.
• [60]Boissy A, Manteuffel G, Jensen MB, Moe RO, Spruijt B, Keeling LJ, Winckler C, Forkman B, Dimitrov I, Langbein J, Bakken M, Veissier I, Aubert A: Assessment of positive emotions in animals to improve their welfare. Physiol Behav 2007, 92(3):375-397.
• [61]Veissier I, Boissy A: Stress and welfare: two complementary concepts that are intrinsically related to the animal's point of view. Physiol Behav 2007, 92(3):429-433.
• [62]Prunet P, Overli O, Douxfils J, Bernardini G, Kestemont P, Baron D: Fish welfare and genomics. Fish Physiol Biochem 2012, 38(1):43-60.
• [63]Désautés C, Bidanel JP, Milan D, Iannuccelli N, Amigues Y, Bourgeois F, Caritez JC, Renard C, Chevalet C, Mormède P: Genetic linkage mapping of quantitative trait loci for behavioral and neuroendocrine stress response traits in pigs. J Anim Sci 2002, 80(9):2276-2285.
• [64]Biscarini F, Bovenhuis H, van der Poel J, Rodenburg TB, Jungerius AP, van Arendonk JAM: Across-line SNP association study for direct and associative effects on feather damage in laying hens. Behav Genet 2010, 40(5):715-727.
• [65]Poissant J, Reale D, Martin JGA, Festa-Bianchet M, Coltman DW: A quantitative trait locus analysis of personality in wild bighorn sheep. Ecology and Evolution 2013, 3(3):474-481.
• [66]Hernandez Fernandez M, Vrba ES: A complete estimate of the phylogenetic relationships in Ruminantia: a dated species-level supertree of the extant ruminants. Biol Rev Camb Philos Soc 2005, 80(2):269-302.
• [67]Turri MG, Datta SR, DeFries J, Henderson ND, Flint J: QTL analysis identifies multiple behavioral dimensions in ethological tests of anxiety in laboratory mice. Current biology : CB 2001, 11(10):725-734.
• [68]Hayes B, Goddard M: The distribution of the effects of genes affecting quantitative traits in livestock. Genet Sel Evol 2001, 33(3):209-229. BioMed Central Full Text
• [69]Yang J, Manolio TA, Pasquale LR, Boerwinkle E, Caporaso N, Cunningham JM, de Andrade M, Feenstra B, Feingold E, Hayes MG, Hill WG, Landi MT, Alonso A, Lettre G, Lin P, Ling H, Lowe W, Mathias RA, Melbye M, Pugh E, Cornelis MC, Weir BS, Goddard ME, Visscher PM: Genome partitioning of genetic variation for complex traits using common SNPs. Nat Genet 2011, 43(6):519-525.
• [70]Schütz K, Kerje S, Jacobsson L, Forkman B, Carlborg Ö, Andersson L, Jensen P: Major growth QTLs in fowl are related to fearful behavior: possible genetic links between fear responses and production traits in a Red Junglefowl × White Leghorn intercross. Behav Genet 2004, 34(1):121-130.
• [71]Buitenhuis AJ, Rodenburg TB, Siwek M, Cornelissen SJB, Nieuwland MGB, Crooijmans R, Groenen MAM, Koene P, Bovenhuis H, van der Poel JJ: Identification of QTLs involved in open-field behavior in young and adult laying hens. Behav Genet 2004, 34(3):325-333.
• [72]Buitenhuis AJ, Rodenburg TB, Siwek M, Cornelissen SJB, Nieuwland MGB, Crooijmans R, Groenen MAM, Koene P, Bovenhuis H, van der Poel JJ: Quantitative trait loci for behavioural traits in chickens. Livest Prod Sci 2005, 93(1):95-103.
• [73]Narcisse: a mirror view of conserved syntenies. http://narcisse.toulouse.inra.fr/animals/cgi-bin/narcisse.cgi webcite
• [74]Livestock Genomics http://www.livestockgenomics.csiro.au/sheep/oar3.1.php webcite
• [75]Tanda G, Ebbs AL, Kopajtic TA, Elias LM, Campbell BL, Newman AH, Katz JL: Effects of muscarinic M-1 receptor blockade on cocaine-induced elevations of brain dopamine levels and locomotor behavior in rats. J Pharmacol Exp Ther 2007, 321(1):334-344.
• [76]Hill SY, Weeks DE, Jones BL, Zezza N, Stiffler S: ASTN1 and alcohol dependence: Family-based association analysis in multiplex alcohol dependence families. Am J Med Genet Part B-Neuropsychiatr Genet 2012, 159B(4):445-455.
• [77]Shibata H, Tani A, Chikuhara T, Kikuta R, Sakai M, Ninomiya H, Tashiro N, Iwata N, Ozaki N, Fukumaki Y: Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia. Psychiatry Res 2009, 167(1–2):88-96.
• [78]Sala M, Braida D, Donzelli A, Martucci R, Busnelli M, Bulgheroni E, Rubino T, Parolaro D, Nishimori K, Chini B: Mice heterozygous for the oxytocin receptor gene (Oxtr(+/-)) show impaired social behaviour but not increased aggression or cognitive inflexibility: evidence of a selective haploinsufficiency gene effect. J Neuroendocrinol 2013, 25(2):107-118.
• [79]Champagne F, Diorio J, Sharma S, Meaney MJ: Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proc Natl Acad Sci U S A 2001, 98(22):12736-12741.
• [80]Feldman R, Zagoory-Sharon O, Weisman O, Schneiderman I, Gordon I, Maoz R, Shalev I, Ebstein RP: Sensitive parenting is associated with plasma oxytocin and polymorphisms in the OXTR and CD38 Genes. Biol Psychiatry 2012, 72(3):175-181.