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RETROSPECT OF BREEDING FOR GENETIC RESISTANCE TO DISEASES IN

POULTRY AND FARM ANIMALS

A. K. DAS*, H. NIANG, A. K. SAHOO S. KUMAR1 AND D. DAS2

Department of Animal Genetics and Breeding F/o Veterinary and Animal Sciences

West Bengal University of Animal and Fishery Sciences37, K. B. Sarani, Kolkata-700 037, West Bengal, India

Review ArticleIndian J. Anim. Hlth. (2019), 58(1) : 21-44

Disease occurs when environmental insult meets genetic predisposition while interaction goes betweenthe genotype of an individual and the environment where it grows. Antigenic drift of the pathogensusualiy has minor or no effects on the polygenic type of defense mechanisms which include a variety ofdifferent physiological and anatomical characteristics acting together to invoke resistance. There ispotential for selecting for resistance between and within populations as genetic variation in diseases isubiquitous, and genetically heterogenous populations are important in maintenance of resistance. Geneticcontrol of disease can be advanced through selecting locally adapted breeds, selective breeding utilizingdisease resistant individuals, and implementing cross-breeding methods to introgress the resistant genes.Integration of chemotherapeutic agents and antibiotics management, vaccination protocols, grazingand nutritional management, culling and stress reduction practices along with other measures mustaccompany genetic approaches to reduce the impact of livestock disease on profitability and animalwell being.

Key words : Disease resistance, Genetic selection, Immuneresponse and immunomodulation,MAS, Transgenic breeding

*Corresponding author1Division of Avian Genetics and Breeding, ICAR-Central Avian Research Institute, Izatnagar-243122, U.P.2ICAR- Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, U.P.

Poultry and farm animals constitutelivestock sector, an integral part of rurallivelihoods, agriculture, national economyand community development. Diseaseaffects the sustainability and

competitiveness of a community (Whitelawand Sang, 2005) and diseases affectinglivestock can have a significant impact onanimal productivity and production, humanhealth, and consequently, on the overall

process of economic development(Jovanovic et al., 2009). Disease costsdirectly as high as 35–50% of turnoverwithin the livestock sector in the developingworld (Bishop and Woolliams, 2014)excluding underlying indirect andintangible costs disease variably incurswhile food safety and quality (residues inlivestock products) is concerned and diseaseposes zoonotic threats to human health,renders reservoir host for infections, createspressures on breeders to address welfareissues and to reduce the reliance ofproduction systems on conventional controlstrategies. Further, unjudicious use ofchemotherapeutic agents, antibiotics andvaccination protocols have most frequentlyhad negative consequences by promptingvariability among micro-organisms andinducing appearance of drug-resistantstrains, which has resulted further in seriousanimal healthcare problems and adverseeffects on environment. Hence, diseaseimpacts are often considered to be aqualitative function of direct economicimpact, industry and public concern,zoonotic potential and impacts on animalwelfare and international trade (Davieset al., 2009; Bishop and Woolliams, 2014).Keeping these aspects in view, presentstrategy strives for sustainable control ofdiseases by integration of herbalchemotherapeutic agents and antibioticsmanagement, vaccination protocols,grazing management, nutritionalmanagement, biological and genetic controlunderstanding host-pathogen interaction.Breeding programs with the goal of

enhancing resistance to diseases may helpto alleviate the problems for long time.Selection of livestock with natural andacquired resistance to disease is one suchoption for alternative control of disease(Selvam and Panneerselvam, 2014). For asubset of diseases, it may be both feasibleto measure resistance traits on sufficientanimals to determine genotypes forresistance and economically worthwhile toincorporate such traits into breeding goals(Bishop and Woolliams, 2014). Hence,genetics of disease resistance, genomictools in selecting resistance phenotypes, itssustainability and introgression intodeserving population were reviewed andaccordingly breeding strategy was framedfor enhanced resistance to diseases inlivestock.

Concepts of disease resistance,tolerance and resilienceThe disease resistance is inherently arelative term rather than absolute andimplicitly confuses infection (invasion bya pathogen or parasite) with disease (thenegative consequences of being infected)(Bishop and Woolliams, 2014). From anecological consideration of the interactionbetween the host and the pathogen species(Grenfell and Dobson, 1995), the concept,resistance may be defined as the ability ofthe host to exert some degree of control overthe pathogen life cycle (Bishop, 2012;Bishop and Stear, 2003) or to resistinfection (Jovanovic et al., 2009), whiletolerance signifies a condition in which theinfected host displays very limited adverse

Indian Journal of Animal Health, June, 201922

effects (Jovanovic et al., 2009) as the netimpact on performance of a given level ofinfection, i.e. the regression of performanceon (a function of) pathogen load and arelated concept, resilience implies theproductivity of an animal in the face ofinfection (Bishop and Woolliams, 2014).Whereas resistance refers the ability of ahost exerting a deleterious influence on thefitness of the pathogen, hosts with a greatertolerance are those able to maintain agreater fitness as pathogen load increases(Bishop and Woolliams, 2014). If our goalis to stop the spread of infection to anotherpopulation, then resistance is far moreadvantageous than tolerance (Jovanovicet al., 2009). If a correlation exists betweenthe resistance, tolerance and/or resilience,then there may be applicable an equation,Wi = ai +biI; where a

i is the fitness when

uninfected, I is the infection intensity, Wi

is the actual fitness of host type i, bi is what

shows us tolerance (i.e. the slope ofrelationship between W and I) (Stoweet al., 2000). As immune response alters atan individual level with continuingexposure to infection even conditioninghusbandry and environment as constant aspossible, it is difficult to measure the changein performance as pathogen load changesto assess tolerance but can only be measuredfor those diseases with weak immunememory and the traits expressed repeatedlythrough life (Bishop and Woolliams, 2014).Again to assess tolerance requiring differentinfection levels on an individual animal canbe overcome to some extent by consideringhost genetics at the family level where sire’s

genetic merit can be considered as areaction norm based on observations on itsoffspring with different pathogen burdens,but the family size has to be sufficient tominimize between-sib variability (Bishopand Woolliams, 2014). Some of themeasurement issues associated withtolerance may be overcome by the host-pathogen interaction trajectories (Doeschl-Wilson et al., 2012), which describe thejoint changes in animal infection level andperformance over time accounting for time-dependent impacts of infection and lendingthemselves to mathematical analyses. Thebigger issue with tolerance is that it is onlyexpressed by the infected animals and tobe useful, requires the disease to be at highprevalence (Bishop, 2012). However,Bishop and Woolliams (2014) could believefor those diseases where prevalence issubstantially less than one, that genomicstudies should focus on resistance traitsrather than tolerance, and in cases whereall animals are infected, then resilienceshould become a useful concept.

AnGR perspective for geneticvariability in disease resistance/toleranceGenetic investigations involving animalresistance to infections caused by pathogensof varying etiologies can be carried out atthree genetic levels i.e. species, breed andindividual to assess animal geneticvariability. The impact of geneticresistance/ tolerance to pathogens is highwhen all levels of genetic resistance/tolerance acts synergistically. Studies on

Breeding for disease resistance 23

species variability in genetic resistance topathogen causing footrot indicate that goatsdisplay a greater resistance to footrot thansheep. When considering the significanceof resistance/tolerance at the breed level,the intrinsic evolutionary advantage ofbreeds that are adapted to an environmentshould be taken into account (Jovanovicet al., 2009). In tropical regions, whereextreme endemic diseases are widespreaddue to their evolutionary roots, locallyadapted autonomous breeds display a fargreater level of genetic resistance/ toleranceand adaptation, as compared to importedbreeds (Savic et al., 1995). Individualvariability and the identification of thoseindividuals whose resistance/ tolerance tothe infective agents can be determinedthrough clinical examination, or estimatingresistance indicator parameters or usinggenentic markers (marker-assisted slection)or genomic tools, represents the first stepin the formation of genetic resistance/tolerance within a population (Jovanovicet al., 2009). Based on the database FAODAD-IS (2007), genetic resistance/tolerance to a variety of diseases, has beenreported in 59 breeds of cattle, 33 breedsof sheep, 5 breeds of horses and three breedsof pigs, all of which confirms that certainbreeds express greater resistance/ toleranceto pathogens than others.

Cattle: Studies on genetic resistance incattle aimed at so-called target diseases,those that cause enormous economic lossor at investigations geared at developingmanagement programs for implementation

in regions where a particular infectiousdisease is endemic in character (Jovanovicet al., 2009). Zebu cattle (Bos indicus)appear to be resistant to foot and mouthdisease (FMD), rinderpest and tick bornediseases, to which European cattle (Bostaurous) are susceptible (Selvam andPanneerselvam, 2014). In Herefold cattle,presence of pigment around the eyeindicates that the animal is resistant to eyeinfections and eye cancer. Selection ofbreeding stock with pigment on eye-lidsdrastically reduces the eye trouble(reviewed in Selvam and Panneerselvam,2014). Rinderpest, mastitis anddermatophilosis were documented for breedresistance; paratuberculosis andsalmonellosis for within-breed resistance;tuberculosis and brucellosis for within andbetween-breed resistance; FMD,trypanosomosis, theileria (T. annulata),East coast fever (T. pava) and babesia forbreed tolerance; and theileria (T. sergenti),helminthosis and ticks-infestation forresistance and tolerance in combination(reviewed in Jovanovic et al., 2009; Bishopet al., 2002).

Sheep and goats: Small ruminants whileraised on grazing system naturally getexposed to parasitic infection caused byhelminths. Sheep and goats displaybetween-species variation in resistance togastrointestinal nematode infections,mycotoxins, bacterial diseases includingfootrot and mastitis, ectoparasites such aslice and scrapie (Selvam andPanneerselvam, 2014). Mastitis,


dermatophilosis and cutaneous myiasis(flystroke) were documented fordemonstrating for breed resistance;paratuberculosis and salmonellosis forwithin-breed resistance; cowdriosis(heartwater), trypanosomosis for breedtolerance; and helminthosis and liver flukeinfestation for resistance and tolerance incombination (reviewed in Jovanovic et al.,2009; Bishop et al., 2002).

Pigs: Special effort identified neonataldiarrhea (E coli F4/F5) and post weaningdiarrhea (E coli F18) with complete resistance(major gene conveys), atrophic rhinitis(Bordetella bronchiseptica) with within andbetween breed resistance, and African swinefever and FMD with within and betweenbreed tolerance (Bishop et al., 2002).Besides, swine brucellosis (Brucella suis),dysentery (Brachyspira hyodysenteriae),eperythrozoonosis (Mycoplasma suis),leptospirosis, salmonellosis, swine influenza,PCV2 associated disease (Porcine circovirustype 2), vomiting and wasting disease(Haemagglutinating encephalomyelitisvirus), Aujeszkys disease (Pseudorabiesvirus), and few parasitoses (Ascaris suum,Sarcocystis miescheriana, Strongyloidesransomi, Trichinella spiralis) were reportedfor genetic variation in resistance topathogens and diseases in swine (Reiner,2009).

Poultry: Marek’s disease, infectiouslaryngitracheitis, avian infectiousbronchitis, Rous sarcoma, pullorum, fowltyphoid, coccidiosis and Ascaridia galli

were documented for demonstrating inbredline resistance; and avian leukosis,infectious bursal disease, and Newcastledisease for between-breed resistance(reviewed in Jovanovic et al., 2009; Bishopet al., 2002). Investigations of geneticresistenace to parasitic infections in poultry,determined that breeds varied significantlyin their level of resistence to coccidiosis. Itwas also determined that individuals of thesame breed can display marked differencesin susceptibility to coccidiosis.

In some cases, the genetic variation isbetween populations (breeds, strains, lines);in other cases, it exists within populations.In either case, there is potential for selectingfor resistance to all these diseases as geneticvariation in diseases is ubiquitous.Genetically heterogenous populations aremost important in regards to diseaseresistance maintenance. Diversepopulations conferring disease resistanceare less susceptible to catastrophic diseaseepidemics and special attention has beenfocused on the importance and possibleadvantages of heteregenous geneticpopulations, particularly in terms of thecomplex responses they confer toepidemics, their duration, decreases inmortality, etc. (Springbett et al., 2003). Dueto their genetic advantages when inresponding to epidemics of catastrohicproportion, the maintenance of geneticheterogeniity in livestock populations iscrucial to maintaining viable livestockpractices and the preservation ofbiodiversity (Jovanovic et al., 2009).


Genetics of disease resistanceDisease occur when environmental insultmeets genetic predisposition (Warner et al.,1987) while interaction goes between thegenotype of an individual and theenvironment where it grows. Resistance orsusceptibility to a certain disease orpathogen is usually controlled by a majorsingle gene locus. The defense mechanismmay be modulated however by unidentifiedloci, including genetic regulatory elements,and by environmental factors. Theexpression of the resistance locus may be aspecific predisposing or conditioning factoramong a series of other factors. Antigenicdrift of the pathogens usually has minor orno effects on this polygenic type of defensemechanisms which include a variety ofdifferent physiological and anatomicalcharacteristics acting together to invokeresistance (Muller and Brem, 1991). Forinstance, fly infestation can be affected byhair/ wool length, skin secretions, hidethickness, and grooming behaviour. Themechanism underlying resistance topathogen can frequently be explained bythe presence or absence of certain moleculesin the host which are critical for infection,recognition, or elimination of the pathogen.Typical example is the majorhistocompatibility complex (MHC) anddisease associations. There are also non-specific defense mechanisms influenced bythe expression of major genes such as theactivity of lysozymes, interferons,chemokines, phagocytes etc. and alsomonogenic deficiencies leading to generalsusceptibility (Muller and Brem, 1991).

The genetic components of diseaseresistance include those that affect theimmune system, as well as virtually everyother system of the body, and the mostimportant environmental component isexposure to the pathogen. If a pathogeninvades first line of defense, the immunesystem has the opportunity to eliminate thepathogenic organism through themobilization of cells and soluble substancesproduced in the primary (bone marrow andthymus) and secondary (spleen and lymphnodes) organs of the immune system. Asreviewed by Warner et al. (1987), cellularimmunity is a function of many types ofleukocytes, including T cells, macrophages,NK cells, LAK cells, etc. B cells functionthrough developing antibody mediatedimmunity. Many other soluble moleculesto mediate immunity are the complementcomponents, interferons, interleukins, andother lymphokines and monokines.Hormones, prostaglandins and leukotrienesalso get involved and cell surface moleculeslike antigen receptor on B cells (BCR) andon T cells (TCR) have a role in regulationof the immune response. The TCRrecognizes antigens in the context ofmolecules encoded by the MHC genes. TheBoLA (bovine), OLA (goat), CLA (sheep),SLA (pig), B complex (chicken) are theMHC in different domestic species andlinked to different specific immunologicalresponses. The high degree ofpolymorphisms (Adams and Templeton,1998) for MHC genes which is unique foreach individual partially explains how thehost immune system can attack such a great


number of antigens which requires theability to distinguish self from foreign. TheMHC encodes four classes of proteinmolecules and comprises of three sub-regions: B-F (Class I), B-G (Class IV) andB-L (Class II), Class III genes mappedoutside the Class I and Class II. Class IVgenes are unique in avian species andexpressed on RBCs. The Class I genes actas restricting dements in T cell recognitionof vitally infected target cells. Thus, the cellreceptor recognizes both foreign antigenand self Class I MHC antigens in order togenerate an immune response. The Class II(immune response, Ir) genes control theinteraction of T cells, B cells andmacrophages in the generation of thehumoral immune response, and participatein some aspects of cellular immunity aswell. The function of Class III genes is tobe part of the complement cascade, whichends with the lysis of the cell or virusparticle to which antibody has bound(Warner et al., 1987). Genetic variation inimmune cell compartments naturally existsand may contribute to varied resistance topathogens (Cheeseman, 2007) as geneticdifferences in lineage commitment ofthymocytes and not selection cause thevariation in CD4 and CD8 T cellpopulations in mice (van Meerwijik et al.,1998) and the MHC genes determine theperipheral T cell ratio (CD4/CD8) in rats(Damoiseaux et al., 1999). The chickenMHC as well as non-MHC genes are knownto influence B cell mediated antibodyresponses to various antigens (Lamont,1991).

There are some non-pathogenic diseasesthat are strictly genetic and do not involvethe immune system. A few of the betterknown examples are sickle cell anemia,which is caused by a single amino acidsubstitution in hemoglobin polypeptidechain; Lesch-Nyan syndrome, which iscaused by the absence of the enzymehypoxanthine-guanine phosphoribosyltransferase; and Tay-Sachs disease, whichis caused by the deficiency of the enzymehexosaminidase A (Warner et al., 1987).Some diseases classified as genetic diseasesmay, in fact, be the inheritance of thereceptors (like cell surface receptor K88 inpig) for a specific pathogen (like E. coli toattach) (Moon et al., 1999). In the immunesystem there are also diseases that arestrictly genetic and not dependent onpathogens. In the presence of a pathogen,the ability of an animal to respondimmunologically resides in many genes thataffect the integrity of the immune system.For instance, the repertoire of cells andantibodies that an individual developsduring ontogeny is under genetic control(Warner et al., 1987).

Genetic selection for disease resistanceAnimal breeding operates through theselection of genetically superior animals forthe important traits exhibiting geneticvariation in the population and thuscharacterized by some degree ofheritability. The rate of genetic progress orof response to selection is a function of theaccuracy of selection, generation intervaland selection intensity. To exploite genetic


variation in disease resistance, theimplications of selection can be wider thanjust its effect on the population undergoingselection, if we recognize the pathogen-hostinteraction pathways to understand theepidemiological consequences of theselection and involve in our approach. Moreimportant is that three facets of immunesystem (the natural, innate, and acquired)must be active and is crucial in developingselection programs for disease resistance.If the breeding goal is to reduce bacterialdiarrhea in young calves, then selectiontraits might include the dam’s geneticpotential for producing specific colostrumantibodies (passive immunity) and the calf’sgenetic potential for developing an innateand acquired immune system early in lifethat responds to the diarrhea causingpathogen. There are negative geneticcorrelations between the dam and calf’sresistance to some diseases (Snowder et al.,2005). In this case, selection index for totalmerit may be feasible to maintainproduction levels while selecting for diseasersesistance. Interactions between thegenetics of the animal and the environmentcommonly exist, and if found significant,animals selected for improved diseaseresistance in one environment may be moresusceptible to the same disease in a differentenvironment. Therefore, selectionprograms may have to be environmentspecific with the selection environmentmatching the commercial productionenvironment. Breeders face challenge toaccurately identify the phenotype fordisease resistance and constraint is the

potential cost associated with measuringdisease resistance.

A. Direct selection for disease resistance:As per Rothschild (1998), it includes sub-clinical or clinical infection and clinicalexpression but it is not ethical at all.Animals with clinical expression of theinfection may be identified with relativeaccuracy but all healthy animals may notbe exposed to the pathogen or challengedequally. Moreover, exposure to theinfection in natural environments is subjectto temporal and spatial clustering of diseaseincidence as diseases often occur in clustersof time (years, seasons, production cycles,etc.) and space (herd, pasture, farm, region,etc.). In seasons when the disease incidenceis high, there can be an increase in theaccuracy of identifying animals with a highprobability of being disease resistant but inseasons of low incidence the accuracy willbe diminished (Snowder et al., 2005).Though this approach provides reliablemeasure of the phenotype, but ideally itshould take place in a highly controlled andisolated environment, hence not practicalthe approach. The second approach is touniformly challenge all breeding stock withinfection which requires isolation of thepopulation to prevent transmission to non-breeding stock. This approach can be costlydepending upon the pathogen’s virulenceand clinical expression of the disease but isa reliable measure of disease resistance. Athird approach is to challenge relatives orclones of the breeding stock while thedisease has a high mortality rate, and is a


reliable method of determining geneticresistance. The latter two approaches arenot without error because immunologicalbackground (previous exposure to thepathogen) may vary among animals whichis to be determined for biasing the observedanimal response to a disease challenge. Incattle, direct selection for reducingbrucellosis had a favorable response asevidenced when Templeton et al. (1990)bred cows to a naturally resistant bull.

B. Indirect selection for diseaseresistance: It could be achieved byselecting for indicators of disease resistancewhich include pathogen products (i.e.pathogen reproductive rates, pathogenbyproducts), and biological orimmunological responses of the host. Oneof the most successful approaches ofindirect selection for disease resistance wasreported in sheep by selecting for low fecalinternal parasite egg count (Woolastonet al., 1992). In dairy cattle, somatic cellcount is used as a selection criterion forreducing mastitis (Shook and Schutz,1994). A higher haemolytic complementactivity can be an indicator for higherresistance to tick infestation and subsequenttick borne diseases (Wambura et al., 1998).Immune responsiveness, challenging ananimal with an antigen or vaccine andmeasuring in vivo antibody response orproduction is an indicator of diseaseresistance (Buschmann et al., 1985; Gavoraand Spencer, 1983) and has been mostuseful in poultry (Lamont et al., 2003) andswine (Mallard et al., 1992). Hernandez

et al. (2003) suggested that immuneresponsiveness would be a useful indicatorof disease resistance in cattle. One of theimportant non-pathogenic multi-determinant antigens to monitor immuneresponsiveness in poultry is sheeperythrocytes (SRBC) (Siegel and Gross,1980). Birds eliciting higher antibodyresponse against SRBC also produce moreantibodies to a variety of antigens(Parmentier et al., 1998). The non-specificcomponents of immune system includephagocytic and bactericidal actions ofperipheral blood monocytes, macrophages,lysozyme (Das et al., 2016; Lacey et al.,1990),and neutrophil metabolic andphagocytic activity and lymphocyteblastogenesis in response to antigens. Useof mitogens as an indicator of cell-mediated response revealed geneticdifferences in poultry for T cell mitogensphytohaemagglutinin and concanavalin(reviewed in Ilaya Bharathi et al., 2016;Buschmann et al., 1985). The IgG is themost abundant immunoglobulin in serumand regarded as an indicator of generalimmune response (Pinard van der Laanet al., 1998). The bird’s ability to mountantibody responses to other antigen isprimarily revealed by serum IgGconcentration which is traceable in all bodyfluids. van der Zijpp (1983) detailed thegenetic components involved in immuneresponse and resistance to viruses causingMarek’s disease, lymphoid leukosis andNewcastle disease. Meeker et al. (1987)found no evidence for nonadditive geneticcontrol (heterosis) of immune response toPseudorabies or B. bronchiseptica vaccines,


but additive genetic control and breeddifferences. Edfors et al. (1985) reportedsignificant sire effects on immune response,indicating genetic influence of immuneresponse to E. coli antigens. Furtherinvestigations (Kokate et al., 2017abc; Daset al., 2016; Gupta et al., 2010; Sivaramanet al., 2005) revealed that humoralresponse to antigens like SRBCs, NDvaccine, GAT etc. had polygenicinheritance with moderate heritabilityestimates, cell mediated immune responsehad polygenic inheritance with low tomoderate heritability estimates,phagocytosis had additive gene controlwith major gene effect, and combining allthese three facets constituteimmunocompetence index. Gavora andSpencer (1983) suggested that theheritability estimates of the humoralimmune response correspond well toresistance to a disease caused by aparticular pathogen. Of course, theestimates of heritability do not indicatewhich genes or how many genes areinvolved in the control of a particular trait,however, demonstrate which diseases havea strong additive genetic component, andwould therefore be most responsive tobreeding for increased disease resistance(Warner et al., 1987). Selection forimmune response is generally beneficialwhen a single disease is targeted. Foreffective selection, indicator traits must beheritable, highly genetically correlatedwith resistance to the disease or diseasesof interest, accurate to measure, andaffordable.

C. Genomic selection for diseaseresistance: Genomic selection for geneticresistance to disease needs identification ofspecific resistance genes or genetic markerslinked to the phenotypes of diseaseresistance trait and the benefit of thisapproach is the ability to select animalsusing DNA-based selection withoutexposure to infection in a challenge test, ornecessity of a natural epidemic (Bishop andWoolliams, 2014). This can be achieved ifmajor genes or QTL for resistance can beidentified, or SNP-chip based genomicpredictors (Meuwissen et al., 2001) ofsufficient accuracy developed. WithoutDNA-based predictions, selection accuracywill depend on either routine challengetesting or continuous disease prevalence inthe field, to enable calculation of expectedbreeding values (EBVs) based on expressedresistance phenotypes (Bishop andWoolliams, 2014). The complexity of theimmune system clearly infers that manysingle genes, major genes, MHC and non-MHC genes are involved in diseaseresistance and can be exploited forscreening of resistance and selection. Fewexamples of single genes influencingdisease resistance in livestock include thefimbriae F4 (K88) gene in swine forreducing E. coli intestinal infection (Moonet al., 1999), the prion protein (PrP) generelated to scrapie susceptibility in sheep(Bossers et al., 1999), and the TNC generelated to salmonellosis in chickens (Huet al., 1997). The Nramp1 gene (naturalresistance-associated macrophage protein)associated with innate immune system gets


linked with resistance to brucellosis(Harmon et al., 1989), tuberculosis andsalmonellosis (Qureshi et al., 1996).Homologues for Nramp1 was identified,sequenced and/or mapped in chickens,swine and sheep (Adams and Templeton,1998). B-haplotype (B21 allele) associatedwith MD resistance (Bacon and Witter,1994; Hedemand et al., 1993), Tv and evgenes controlling/ influencing resistance toALV (Payne and Nair, 2012; Bacon et al.,2000) are few examples of major genes.Variability within BoLA complex providesan opportunity for identifying alleles withsignificant effect on the expression ofresistance to mastitis (Yongerman andSaxton, 2004). Particular loci on OLAcomplex are associated with geneticresistence to parasites, such as Haemonchuscontortus, Trichostrongyus columbriformisand Ostertagija circumcinta in sheep(Jovanovic et al., 2009). Class II MHCgenes are associated with MD and Coccidiaresistance, Class IV with Coccidiaresistance and B-F/B-L region genes withresistance and susceptibility to pathogens.The B complex was reported to beassociated with resistance to Marek’sdisease, Rous Sarcoma virus, fowl cholera,and lymphoid leukosis viruses (van derZijpp, 1983), and the immune response tosynthetic antigens, bovine serum albumen,Salmonella pullorum bacterium, total IgGlevels, and cell-mediated responses(Lamont and Dietert, 1990). The examplesof non-MHC genes are Cytokine genes(IFN gamma and IL-2), Cytokine promotergenes (IFN gamma and IL-2 gene

promoter), Cytokine Receptor gene(IL-2 receptor), Toll-like receptors,Chemokines, Inducible Nitric oxide,Arginase etc. Cytokines have regulatoryand signaling role in immune responses.The abnormal levels of IL-2 are associatedwith many disease problems or immunedisorder, and polymorphism at regulatorysequences is associated with antibodyresponse. SNP (2781G>T) IFN- gene inHolstein, Jersey and Brahman-Anguscrosses has association with Mycobacteriumavium subspecies paratuberculosis (MAP)infection (Pinedo et al., 2009). Toll-likereceptor (TLR) activation on antigenpresenting cells results in the production ofnumerous cytokines such as IL-12 and IL-10, and chemokines such as CXCLi2 andCCLi2, and critical to this innate immuneresponse is the signal transductionmolecule, NF-κB (Li and Stark, 2002;Luster, 2002). Chemokines affect growthand differentiation of haematopoetic cellsand its normal expression is necessary forthe host defense. Inducible nitric oxide/ NOsynthase type 2 (NOS-2 or iNOS) has a rolein immunity against viruses (Herpessimplex type-1, Vaccinia, Japaneseencephalitis), bacteria (tuberculosis) andparasites (leishmania, malaria). Forexample, bovine CARD15/NOS-2(chromosome 18) plays an important rolein TB resistance (Cheng et al., 2016; Qinet al., 2015). In pathological conditions likeasthma, arthritis, Psoariasis, diabeticcomplications, trauma, breast cancer,glomerulonephritis and infectious diseases,there is enhanced activity of arginase, and


selective arginase inhibitors or downregulation of arginase can be a controlmeasure of such disases.

New and novel gene mapping approachesare being developed specifically fordetection of complex disease loci (Pareeket al., 2002). Micro array technology isadvancing rapidly to enable association oflivestock DNA with mice and human DNA(Chitko-McKown et al., 2004). Global geneexpression profiling with the help ofMicroarray unravels that NFKBID, BoLA-DQB, HOXA13, PAK1, TGFBR2,NFKBIA genes are associated with T.annulata infection (Kumar et al., 2017).Comparative genomics may make theidentification of disease loci easier andmore affordable.

Marker-assisted selection (MAS): Thegenetic markers can be used to locate genesunderlying phenotypic traits on thecorresponding genome maps using linkagestrategies. This mapping is the first step inthe process referred to as positional cloningwhich culminates in the isolation of thecausal gene and mutation. The novel markerassisted selection scheme strives foridentification of quantitative trait loci(QTL) (Wilmut et al., 1992) and is expectedto increase genetic response by affectingthe factors: increase genetic variation (themolecular substrate of breeding programs),increase the accuracy of selection, reducethe generation interval and increase theselection intensity. Mapping genesexplaining breed differences for

economically important traits and diseaseresistance are potential for the geneintrogression by marker aidedbackcrossing, thus increasing the geneticvariation usable as substrate for selectionprograms. Adding information on mappedQTL on top of their own performance dataand that of relatives will increase accuracyof selection especially by explainingMendelian sampling variance. As themarker genotype is obtainable at virtuallyany stage of development and irrespectiveof sex, there is considerable potential forreduction in generation interval. Finally,marker genotyping will becomeconsiderably cheaper than phenotypecollection allowing selection for more traitsamongst more individuals than theconventional approach, thus increasing theselection differential or intensity. Forepidemic diseases, it is necessary to developtechniques for selection based on markeralleles associated with enhanced diseaseresistance (Bishop and Woolliams,2014).Moreover, understanding the molecularbiology underneath complex traits mightreveal novel mechanisms of gene actionrequiring adjusted selection schemes fortheir optimal exploitation. Selection forresistance based on specific B alleles withinthe MHC has been used for many years toassist in the management of the Marek’sdisease. Researchers have identified anumber of QTL associated with resistanceto the disease (Yonash et al., 2001) andmarkers for dermatophilosis in cattle(Maillard et al., 2003), scrapie in sheep(Hunter et al., 1996), diarrhoea caused by


E. coli in pigs (Edfors and Wallgren, 2000).Attempts are being made to explore manymarkers (reviewed in Prajapati et al., 2017)for its accurate implication for selection ofthe traits of disease resistance orsusceptibility, such as SNP G29A mutationin the 5’ UTR of the ITGB6 gene(chromosome 2) associates with resistanceto FMD infection in the zebu cattle (Singhet al., 2014), ATP1A1 (chromosome 3)polymorphism with the mastitis trait inHolstein cows (Liu et al., 2012), bovineCARD15/NOS-2 (chromosome 18) withTB susceptibility (Cheng et al., 2016; Qinet al., 2015). In piglets, a receptor (K88) inthe intestinal tract to which a particularstrain of E.coli adheres, being geneticallydetermined, a commercially available DR2gene marker test allows routineidentification of genetically resistantindividuals, and a DR1 gene marker testfurther identifies those individualssusceptible to F18 E. coli. The utilizationof these tests during breeding practices hassignificantly increased genetic resistance inthose populations where it has beenimplemented (Edfors and Wallgren, 2000).

Breeding strategy for resistance todiseasesFor practical purposes, investigators willnormally focus their attention on twophenotypic disease susceptibility classes(afflicted/ not afflicted animals) in whichcontinuous variation is disregarded.However, due to the existence of unknowncontinuity-causing factors which becomenoticeable above certain threshold level,

disease susceptibility may varydiscontinuously, thus necessitating geneticanalyses to be carried out quantitativelyrather than qualitatively (Muller and Brem,1991). The continuous variable underlyingthese phenomena has been termed asliability. Falconer (1967) has calculated thecorrelation of liability between relatives ofany specified sort and the heritability. If atrait like disease resistance must be includedin a breeding programs, animal breederswill have to consider genetic variability andheritability, economic value, possibilitiesand costs for recording data andexploitation of of marker traits and genes.Although disease trait heritabilities arenormally low, the genetic variation ofdisease incidence is economically importantand justifies the inclusion of disease traitsin breeding programs (Muller and Brem,1991). Progress in resistance breedingrequires long-term strategies, and is limitedand delayed by at least two factors:inadvertent enhancement of susceptibilityto a disease by selection for specificresistance to another disease, and lack ofstrategies allowing selection for overallresistance. Conventional breeding strategiesfor disease resistance whereas has at leasttwo advantages: automatic inclusion of allgenetic host factors influencing resistanceor susceptibility, and selection for theresistant trait being independent of shiftsin environmental factors and diseaseprofiles over time. Although it has theprincipal disadvantages of low heritabilityof resistance traits necessitating expensiveprogeny testing with prolonged generation


intervals, moderately defined heterogeneityof the disease traits, and antagonisticrelationship of resistance and performancetraits (Muller and Brem, 1991). Dependingupon disease etiology and the availablyanimal genetic resources, the strategy foradvancing genetic control of disease can beestablished through the selection of locallyadapted breeds, the implementation ofcross-breeding methods geared atintroducing genes significant in theexpression of genetic resistance/tolerancetowards pathogens, and the selection ofindividuals highly resistant to pathogens(Jovanovic et al., 2009).

Selective breeding to take advantage ofwithin breed variation in disease resistanceis an important strategy in the control of anumber of diseases. For endemic diseases,which are a continuously present in therelevant production systems (e.g. mastitis,helminthosis), selection based onphenotypic response to disease challengeis possible. The indicator traits of diseaseresistance are routinely recorded in dairyherds, and their variation has a large geneticcomponent. With the previously presentedevidence of genetic control of immuneresponsiveness and the obvious naturalselective advantage of resistant animals, itwould seem inevitable that selectivebreeding for improved production traitswould have improved resistance in animals.This has not been the case. One reasonmight be that modern management, whichincludes vaccination, preventive medicationand separation of animals from pathogens,

masks the genetic capacity of the animalsto resist disease. In addition, some genesmay have pleiotropic effects antagonisticto improving both production traits andresistance (Warner et al., 1987). Theexistence of an antagonistic relationshipbetween genetic merit for production traitsand susceptibility to the disease haspromoted interest in selection for resistance.Information on genetic correlations amongdisease resistance, immune responseparameters and production traits are scarce.Gavora and Spencer (1978) explains that itis impossible to distinguish between effectsdue to disease and those due to geneticpotential when estimating geneticcorrelations in populations where diseaseis present. Many dairy cattle breedingprograms, therefore, include increasingresistance to mastitis as an objective.Interest is growing in integrated parasitemanagement (IPM) programs, of whichbreeding for genetic resistance is acomponent. Selective breeding of sheep onthe basis of faecal egg count (FEC) wouldbe an effective means of reducing the needfor treatment with anthelmintics and ofreducing the contamination of pastures withthe eggs of nematode parasites (Woolastonand Windon, 2001).

Keeping critical view upon dissection ofgenetics of disease resistance in livestock,its production parameters and sustainablemaintenance of resistance and animalproduction, we suggest the breedingstrategy taking consideration of thesefollowing initiatives:


(a) Selection of locally adapted breedstaking their intrinsic evolutionaryadvantage,

(b) Selection of those parents that producethe progeny with the lowest incidenceof disease,

(c) Genetic selection of animals for highimmune response using an index thatcombines estimated breeding valuesfor several immunological traits orgenetic markers for QTL analysis,

(d) Selective breeding to take advantageof within breed variation in diseaseresistance,

(e) Use of a breeding stock possessingcertain MHC alleles, which areinvolved in the regulation of theimmune response, including immunefunction traits with high heritability inbreeding programs,

(f) Introgresion of disease resistance genesinto the productive breeds followed byMAS aided backcrossing with theresistant individual as recurrent parent,

(g) Maintaenance of geneticallyheterogenous populations.

After all, present strategy strives forsustainable control of diseases by integrationof herbal chemotherapeutic agents andantibiotics management, vaccinationprotocols, grazing management, nutritionalmanagement, culling and stress reductionpractices, biological and genetic controlunderstanding the host-pathogen interaction.

Genetic modification approach fordisease resistanceGenetic modification offers alternativestrategy to traditional animal breeding andis likely to have speciûc application wheregenetic variation does not exist in a givenpopulation or species and where novelgenetic improvements can be engineered(Whitelaw and Sang, 2005). With eitherapproach, the intention would be to enhancethe ability of the animals to mount anappropriate immune response against thepathogen (which could require dampeningdown the immune system at strategicstages) or to generate an effective systemthat would directly block pathogen entryor directly destroy the pathogen (Whitelawand Sang, 2005). For instance, the Mx genesin mice has the functional alleles to inducea potent antiviral state in response toinfection by specific groups of viruses,including influenza (Whitelaw and Sang,2005), whereas in most commercial chickenlines, the allele of Mx gene is apparentlynot functional due to a single amino acidsubstitution (Ko et al., 2002). There arevarious possible strategies, as listed below,and the authors anticipate that currentefforts in disease biology will enable moreto be devised:

Dominant-negative proteins: Theintroduction of mutant versions of keyfactors in pathogen infection, such as cellsurface receptors, can block diseaseprogression (Ono et al., 2004).

RNA interference (RNAi): This strategy


relies on the ability of speciûc short RNAsequences to anneal with the RNA of thepathogen, causing destruction of the foreignRNA. RNAi requires access to the targetRNA, which may limit this approach toviruses (Clark and Whitelaw, 2003;Tiscornia et al., 2003).

RNA decoys: Expression of RNAsequences that mimic speciûc sequenceswithin a pathogen can disrupt the activityof the pathogen’s replication machinery(Luo et al., 1997). Again, this approach isprobably restricted to specific viruses, withinfluenza being a good candidate.

Immunomodulation by CpG motifs:Bacterial DNA contains non-methylatedcytosine-phosphodiester-guanine (CpG)dinucleotide motifs in higher frequency,when introduced in mammalian systemrecognized as danger signals forpathogen associated molecular pattern(PAMP) (Medzhitov and Janeway, 2000)and immune response is induced. Inmammals, CpG are less in frequency, C ismethylated and C is upstream and G isdownstream to CpG, which suppressstimulatory properties. Syntheticolignodeoxynucleotides (ODN) (motif: 52X

1X

2CGY

1Y

232 , where X

1 is a purine, X

2

is a purine or T and Y1 and Y

2 are

pyrimidines; GTCGTT: optimal motif andAACGTT: suboptimal motif, as recognizedby TLR-9) may be used for immunestimulation as it has potentimmunostimulatory effect in numerousvertebrate species. The CpG-ODN

stimulate B-cells, monocytes, macrophages,dendritic cells, NK cells, upregulate MHCI & II and cytokines and in vitro activity ofCpG-ODN is species-specific (Babiuket al., 2003; Krieg, 2002; Klinman et al.,1996). Prior administration of CpG-ODNprotects against bacteria (L. monocytogenis,E. coli etc.), enhance innate immunity andcan enhance immunogenecity of DNAvaccines (Krieg, 2002). CpG-ODN can shiftthe immune response to a Th1-dominatedcytokine pathway thus explaining thepredominance of Th1-like responses whenCpG-ODN is used as an adjuvant withsubunit or conventional vaccines(Zimmermann et al., 1998; Chu et al.,1997).

Transgenic breeding: While conventionalbreeding strategies as well as MAS arerestricted to the exploitation of geneticvariation pre-existing within the species, ifnot breed of interest, transgenics has openedthe exciting possibility to exploit variantsacross species barriers or even create denovo. The approach of gene targeting oftotipotent embryonic stem cells in culturefollowed by either nuclear transfer inenucleated oocytes or microinjection intoblastocysts mediated by homologousrecombination is locus-specific for theproduction of transgenic animals (Campbellet al., 1996). Besides enhancing growth andimproving carcass characteristics, woolproduction, milk production and alteringmilk composition, transgenic breedingcould increase disease resistance inlivestock. However, the application of


transgenics applied to livestock species hasproven most successful so far in the area ofgene-pharming or the use of livestockspecies as expression systems for theproduction of high value protein products.The transgenic production of antibodies inthe host animal may act in an analogousmanner to vaccination (Kolb et al., 2001;Sola et al., 1998).

It may be concluded that enhancement ingenetic resistance to diseases may be givendue emphasis for maintaining a balancebetween production and disease resistancestatus of animals. The potential seems greatfor identifying breeding stock that ishealthier because of their immuneresponsiveness. Although it may be difficultto select for animals’ resistance to a widerange of diseases, it may be possible to

breed or identify animals that aregenetically more responsive to multi-determinant antigens or vaccines. Suitablemolecular marker or marker traits may beidentified for marker-assisted selection anddeveloping disease resistant populations.Certainly, genetic selection will not solveall of our livestock disease problems.Therefore, integration of chemotherapeuticagents and antibiotics management,vaccination protocols, grazingmanagement, nutritional management,culling and stress reduction practices alongwith other measures must accompanygenetic approaches to reduce the impact oflivestock disease on profitability and animalwell being. The research efforts may befurther strengthened for betterunderstanding of genetic mechanisms ofdiseases resistance vis a vis production.

REFERENCESAdams LG and Templeton JW, 1998. Genetic

resistance to bacterial diseases ofanimals. Rev Sci Tech Off Int Epiz, 17:200-219

Babiuk LA, Gomis S and Hecker R, 2003.Molecular approaches to diseasecontrol. Poult Sci, 82: 870-875

Bacon LD and Witter RL, 1994. Serotypespeciûcity of B haplotype inûuence onthe relative efûcacy of Marek’s diseasevaccines. Avian Dis, 38: 65-71

Bacon LD, Hunt HD and Cheng HH, 2000. Areview of the development of chickenlines to resolve genes determining

resistance to diseases. Poult Sci, 79:1082-1093

Bishop SC, De Jong M and Gray D, 2002.Opportunities for incorporating geneticelements into the management of farmanimal diseases: policy issues.Commission on Genetic Resources forFood and Agriculture, FAO, Rome,pp36

Bishop SC and Stear MJ, 2003. Modeling ofhost genetics and resistance toinfectious diseases: understanding andcontrolling nematode infections. VetParasitol, 115: 147-166


Bishop SC, 2012. A consideration ofresistance and tolerance for ruminantnematode infections. Front LivestGenomics, 3: 168/1-7; https://doi.org/10.3389/fgene.2012.00168

Bishop SC and Woolliams JA, 2014.Genomics and disease resistance studiesin livestock. Livest Sci, 166: 190-198

Bossers ME, Harders FL and Smits MA, 1999.PrP genotype frequencies of the mostdominant sheep breed in a country freefrom scrapie. Archiv Virol, 144: 829-834

Buschmann H, Kransslich H, Herrmann H,Meyer J and Kleinschmidt A, 1985.Quantitative immunological parametersin pigs– Experiences with theevaluation of an immunocompetenceprofile. Z. Tierz. Zuchtungsbiol, 102:189-199

Campbell KHS, McWhir J, Ritchie WA andWilmut I, 1996. Sheep cloned bynuclear transfer from a cultured cellline. Nature, 380: 64-66

Cheeseman JH, 2007. Avian immunology,immunogenetics, and host immuneresponse to Salmonella enterica serovarenteritidis infection in chickens.Retrospective Thesis and Dissertations.15855. https://lib.dr.iastate.edu/rtd/15855.

Cheng Y, Huang C and Tsai HJ, 2016.Relationship of bovine NOS-2 genepolymorphisms to the risk of bovinetuberculosis in Holstein cattle. J VetMed Sci, 78(2): 281-286

Chitko-McKown CG, Fox JM, Miller LC,Heaton MP, Bono JL et al., 2004. Geneexpression profil ing of bovinemacrophages in response to Escherichiacoli 0157:H7 lipopolysaccharide. DevComp Immunol, 28: 636-645

Chu RS, Targoni OS, Krieg AM, Lehmann PVand Harding CV, 1997. CpGoligodeoxynucleotides act as adjuvantsthat switch on T helper 1 (Th1)immunity. J Exp Med, 186: 1623-1631

Clark J and Whitelaw B, 2003. A future fortransgenic livestock. Nature Rev Genet,4(10): 825-833

Damoiseaux JG, Cautain B, Bernard I, MasM, van Breda Vriesman PJ et al., 1999.A dominant role for the thymus andMHC genes in determining theperipheral CD4/CD8 T cell ratio in therat. J Immunol, 163: 2983-2989

Das AK, Kumar S, Mishra AK, Rahim A andKokate LS, 2016. Estimating geneticparameters of immunocompetent traitsin Rhode Island Red chicken. Ind JAnim Sci, 86(9): 1015-1020

Davies G, Genini S, Bishop SC and GiuffraE, 2009. An assessment of theopportunities to dissect host geneticvariation in resistance to infectiousdiseases in livestock. Animal, 3: 415-436

Doeschl-Wilson AB, Bishop SC, KyriazakisI and Villanueva B, 2012. Novelmethods for quantifying individual hostresponse to infectious pathogens for


genetic analyses. Front LivestGenomics, 3: 266/1-9; doi: 10.3389/fgene.2012.00266

Edfors LI, Gahne B and Petersson H, 1985.Genetic influence on antibody responseto two Escherichia coli antigens in pigs.II. Difference in response betweenpaternal half-sibs. Z. Tierz. Zuchtunsbiol,102: 308-3017; https://doi.org/10.1111/j.1439-0388.1985.tb00 700.x

Edfors LI and Wallgren P, 2000. Escherichiacoli and Salmonella diarrhoea in pigs,In: Axford RFE et al. (Ed.) 2000.Breeding for resistance in farm animals.Wallingford, Oxon, UK; CABI Pub(New York), pp253-267

Falconer DS, 1967. The inheritance of liabilityto diseases with variable age of onset,with particular reference to diabetesmellitus. Am J Hum Genet, 31: 1-20

FAO DAD-IS, 2007. The state of Agriculturalbiodiversity in the livestock sector:Animal genetic resources and resistanceto disease. Section E, pp101-111

Gavora JS and Spencer JL, 1978. Breeding forgenetic resistance to disease: Specific orgeneral? World’s Poult Sci J, 34: 137-148

Gavora JS and Spencer JL, 1983. Breeding forimmune responsiveness and diseaseresistance. Anim Blood Gr BiochemGenet, 14: 159-180, https://doi.org/10.1111/j.1365-2052.1983.tb01070.x

Grenfell BT and Dobson AP, 1995. Ecologyof infectious diseases in natural

populations. Cambridge UniversityPress, Cambridge, UK

Gupta T, Kumar S, Prasad Y and Kataria MC,2010. Genetics of immunocompetencetraits in White Leghorn chickendivergently selected for humoralresponse to sheep erythrocytes. Ind JPoult Sci, 45(1): 18-21

Harmon BG, Adams LG, Templeton JW andSmith R, 1989. Macrophage function inmammary glands of Brucella abortus-infected cows and cows that resistedinfection after inoculation of Brucellaabortus. Am J Vet Res, 50: 459-465

Hedemand JE, Sorensen P, Ducro BJ andSimonsen M, 1993. Resistance toMarek’s disease associated with B21-l ike haplotypes. Archiv furGeflugelkunde, 57(2): 73-76

Hernández A, Karrow N and Mallard BA, 2003.Evaluation of immune responses of cattleas a means to identify high or lowresponders and use of a human microarrayto differentiate gene expression. GenetSelect Evol, 35: S67-S81

Hu J, Bumstead N, Burrow P, Sebastiani G,Olien L et al., 1997. Rsistance tosalmonellosis in the chicken is linkedto Nramp1 and TNC. Genom Res, 7:693-704

Hunter N, Foster JD, Goldmann W, Stear MJ,Hope J et al., 1996. Natural scrapie in aclosed flock of Cheviot sheep occursonly in specific PrP genotypes. ArchVirol, 141: 809-824


Ilaya Bharathi D, Raj Manohar G andShamsudeen P, 2016. Selectionmethods for disease resistance inpoultry– An overview. Int J Sci EnvirTechnol, 5: 810-815

Jovanovic S, Savic M and Zivkovic D, 2009.Genetic variation in disease resistanceamong farm animals. Biotech AnimHusb, 25(5-6): 339-347

Klinman DM, Yi AK, Beaucage SL, ConoverJ and Krieg AM, 1996. CpG motifspresent in bacterial DNA rapidly inducelymphocytes to secrete interleukin 6,interleukin 12, and interferon gamma.Proc Nat Acad Sci USA, 93: 2879-2883

Ko JH, Jin HK, Asano A, Takada A, NinomiyaA et al., 2002. Polymorphisms and thedifferential antiviral activity of thechicken Mx gene. Genom Res, 12(4):595-601

Kokate LS, Kumar S, Rahim A and Das AK,2017a. Investigatingimmunocompetence in Aseel,Kadaknath and White Leghorn chicken.Ind J Anim Sci, 87(1): 35-38

Kokate LS, Kumar S, Rahim A and Das AK,2017b. Estimating serological immuneresponse against Newcastle diseasevaccine in Aseel, Kadaknath and WhiteLeghorn chicken usinghaemagglutination inhibition test. IndJ Anim Sci, 87(2): 136-138

Kokate LS, Kumar S, Rahim A and Das AK,2017c. Kinetics of serum antibodyresponse to Newcastle disease vaccine

in Aseel, Kadaknath and White Leghornchicken using ELISA. Ind J Anim Sci,87(2): 168-170

Kolb AF, Pewe L, Webster J, Perlman S,Whitelaw CBA et al., 2001. Virus-neutralizing monoclonal antibodyexpressed in milk of transgenic miceprovides full protection against virus-induced encephalitis. J Virol 75(6):2803-2809

Krieg AM, 2002. CpG motifs in bacterialDNA and their immune effects. AnnRev Immunol, 20: 709-760

Kumar A, Gaura G, Gandham R, Panigrahi M,Ghosh S et al., 2017. Global geneexpression profile of peripheral bloodmononuclear cells challenged withTheileria annulata in crossbred andindigenous cattle. Infection, GenetEvol, 47: 9-18

Lacey C, Wilkie BN, Kennedy BW andMallard BA, 1990. Genetic and othereffects on bacterial phagocytosis andkilling by cultured peripheral bloodmonocytes of SLA defined miniaturepigs. Anim Genet, 20: 371-382

Lamont SJ, 1991. Immunogenetics and themajor histocompatibility complex. VetImmunol Immunopathol, 30: 121-127

Lamont SJ, Pinard van der Laan MH, CahanerA, van der Poel JJ and Parmentier HK,2003. Selection for disease resistance:direct selection on the immuneresponse. In: Muir WM and Aggrey SE(Ed.). Poultry Genetics, Breeding and


Biotechnology. CABI Publishing.pp399-418

Lamont SJ and Dietert RR, 1990.Immunogenetics. In: Crawford RD(Ed.). Poultry Breeding and Genetics.Elsevier, Amsterdam.

Li X and Stark GR, 2002. NFκB-dependentsignaling pathways. Exper Hematol, 30:285-296

Liu YX, Xu CH, Gao TY and Sun Y, 2012.Polymorphisms of the ATP1A1 geneassociated with mastitis in dairy cattle.Genet Mol Res, 11(1): 651-660

Luo G, Danetz S and Krystal M, 1997.Inhibition of influenza viral polymerasesby minimal viral RNA decoys. J GenVirol, 78(Pt 9): 2329-2333

Luster AD, 2002. The role of chemokines inlinking innate and adaptive immunity.Curr Opin Immunol, 14: 129-135

Maillard JC, Berthier D, Chantal I, ThevenonS, Sidibe I et al. , 2003. Selectionassisted by a BoLA-DR/DQ haplotypeagainst susceptibility to bovinedermatophilosis. Genet Select Evol, 35(Suppl. 1): S193-S200

Mallard BA, Wilkie BN, Kennedy BW andQuinton M, 1992. Use of estimatedbreeding values in a selection index tobreed Yorkshire pigs for high and lowimmune and innate resistance factors.Anim Biotech, 3: 257-280

Medzhitov R and Janeway C Jr, 2000. Innate

immune recognition: mechanisms andpathways. Immunol Rev, 173: 89-97

Meeker DL, Rothschild MF, Christian LL,Warner CM and Hill HT, 1987. Geneticcontrol of immune response topseudorabies and atrophic rhinitisvaccines: I. Heterosis, generalcombining ability and relationship togrowth and backfat. J Anim Sci, 64:407-413

Meuwissen THE, Hayes BJ and Goddard ME,2001. Prediction of total genetic valueusing genome-wide dense marker maps.Genet, 157: 1819-1829

Moon HW, Hoffmann LJ, Cornick NA,Boother SL and Bosworth BT, 1999.Prevalences of some virulence genesamong Escherichia coli isolates fromswine presented to a diagnosticlaboratory in Iowa. J Vet Diag Invest,11: 557-560

Muller M and Brem G, 1991. Diseaseresistance in farm animals. Experientia,47: 923-929

Ono E, Amagai K, Taharaguchi S, TomiokaY, Yoshino S et al., 2004. Transgenicmice expressing a soluble form ofporcine nectin-1/herpesvirus entrymediator C as a model for pseudorabies-resistant livestock. Proc Nat Acad SciUSA, 101(46): 16150-16155

Pareek CS, Pareek RS and Walawski K, 2002.Novel linkage mapping approach usingDNA pooling in human and animalgenetics I. detection of complex diseaseloci. J Appl Genet, 42: 175-192


Parmentier HK, Walraven M and NieuwlandMGB, 1998. Antibody response andbody weights of chicken lines selectedfor high and low humoralresponsiveness to sheep red blood cells.1. Effect of E.coli lipopolysaccharide.Poult Sci, 77: 248-255

Payne LN and Nair V, 2012. The long view:40 years of avian leukosis research.Avian Pathol, 41(1): https://doi.org/10.1080/03079457.2011.646237

Pinard van der Laan MH, Siegel PB andLamont SJ, 1998. Lessons fromselection experiment on immuneresponse in the chicken. Avian PoultBiol Rev, 9: 125-141

Pinedo PJ, Buergelt CD, Donovan GA,Melendez P, Morel L et al., 2009.Association between CARD15/ NOS-2 gene polymorphisms andparatuberculosis infection in cattle. VetMicrobiol, 134(9): 346-352

Prajapati BM, Gupta JP, Pandey DP, ParmarGA and Chaudhari JD, 2017. Molecularmarkers for resistance against infectiousdiseases of economic importance. VetWorld, 10(1): 112-120

Qin B, Liu T, Xu C, Dong G, Wang S et al.,2015. Correlation study of CARD15gene style polymorphism andsusceptibility of tuberculosis in dairycows. China Anim Husb Vet Med,42(6): 1553-1558

Qureshi T, Templeton JW and Adams LG,1996. Intracellular survival of Brucella

abortus, Mycobacterium bovis (BCG),Salmonnella dublin and Salmonellatyphimurium in macrophages fromcattle genetically resistant to Brucellaabortus. Vet Immunol Immunopathol,50: 55-66

Reiner G, 2009. Investigations on geneticdisease resistance in swine- Acontribution to the reduction of pain,suffering and damage in farm animals.Appl Anim Behav Sci, 118: 217-221

Rothschild MF, 1998. Selection for diseaseresistance in the pig. Proc Nat SwineImprov Fed, Raleigh, North Carolina

Savic M, Jovanovic S and Trailovic R, 1995.Some genetic markers in blood ofBalkan goat. Acta Veterinaria, 45: 5-6

Selvam R and Panneerselvam S, 2014.Genetics of disease resistance inlivestock– the concepts andapplications. Aayvagam Int J MultidiscRes, 2A (5): 15-18

Shook GE and Schutz MM, 1994. Selectionon somatic cell score to improveresistance to mastitis in the UnitedStates. J Dairy Sci, 77: 648-658

Siegel PB and Gross WB, 1980. Productionand persistence of antibodies inchickens to sheep erhtyrocytes. I.Directional selection. Poult Sci, 59(1):1-5

Singh R, Kumar S, Deb R, Sengar G, Singh Uet al., 2014. Development of a tetra-primer ARMS PCR-based assay for


detection of a novel single-nucleotidepolymorphism in the 52 untranslatedregion of the bovine ITGB6 receptorgene associated with foot and-mouthdisease susceptibility in cattle. ArchivVirol, 159: 3385-3389

Sivaraman GK, Kumar S, Saxena VK, SinghNS and Shivakumar BM, 2005.Genetics of immunocompetent traits ina synthetic broiler dam line. BritishPoult Sci, 46(2): 169-174

Snowder GD, van Vleck LD, Cundiff LV andBennett GL, 2005. Influence of breed,heterozygosity and disease incidence onestimates of variance components ofrespiratory disease in pre-weaned beefcalves. J Anim Sci, 83: 507-518

Sola I, Castilla J, Pintado B, Sanchez-MorgadoJM, Whitelaw CB et al . , 1998.Transgenic mice secreting coronavirusneutralizing antibodies into the milk. JVirol, 72(5): 3762-3772

Springbett J, Mackenzie K, Woolliams A andBishop SC, 2003. The contribution ofgenetic diversity to the spread ofinfectious diseases in l ivestockpopulations. Genet, 165: 1465-1474

Stowe KA, Marquis RJ, Hochwender CG andSimms EL, 2000. The evolutionaryecology of tolerance to consumerdamage. Ann Rev Ecol Systematics,31(1): 565-595

Templeton JW, Estes DM, Price RE, Smith Rand Adams LG, 1990. Immunogeneticsof natural resistance to bovine

brucellosis. In: Proc 4th World CongGenet Appl Livest Prod, pp396-399

Tiscornia G, Singer O, Ikawa M and VermaIM, 2003. A general method for geneknockdown in mice by using lentiviralvectors expressing small interferingRNAs. Proc Nat Acad Sci USA, 100(4):1844-1848

van der Zijpp AJ, 1983. Breeding for immuneresponsiveness and disease resistance.World’s Poult Sci J, 39: 118-131; https://doi.org/10.1079/WPS19830012

van Meerwijik JP, Bianchi T, Marguerat S andMacDonald HR, 1998. Thymic lineagecommitment rather than selectioncauses genetic variations in size of CD4and CD8 compartments. J Immunol,160: 3649-3654

Wambura PN, Gwakisa PS, Silayo RS andRugaimukamu EA, 1998. Breedassociated resistance to tick infestationin Bos indicus and their crosses withBos taurus. Vet Parasitol, 77: 63-70

Warner CM, Meeker DL and Rothschild MF,1987. Genetic control of immuneresponsiveness: A review of its use as atool for selection for disease resistance.Anim Sci, 64: 394-406

Whitelaw CBA and Sang HM, 2005. Disease-resistant genetically modiûed animals.Rev Sci Tech Off Int Epiz, 24 (1): 275-283

Wilmut I, Haley CS and Woolliams JA, 1992.Impact of biotechnology on animal


breeding. Anim Reprod Sci, 28: 149-162

Woolaston RR, Elwin RL and Barger IA,1992. No adaptation of Haemonchuscontortus to genetically resistant sheep.Int J Parasitol, 22: 377-380

Woolaston RR and Windon RG, 2001.Selection of sheep for response toTrichostrongylus colubriformis larvae:genetic parameters. Anim Sci, 73: 41-48

Yonash N, Cheng HH, Hillel J, Heller DE andCahaner A, 2001. DNA microsatellites

linked to quantitative trait loci affectingantibody response and survival rate inmeat-type chickens. Poult Sci, 80: 22-28

Yongerman SM and Saxton AM, 2004.Association of CXCR2 polymorphismswith subclinical and clinical mastitis indairy cattle. Dairy Sci, 87: 2442-2481

Zimmermann S, Egeter O, Hausmann S,Lipford GB, Rocken M et al., 1998.CpG oligodeoxynucleotides triggerprotective and curative Th1 responsesin lethal murine leishmaniasis. JImmunol, 160: 3627-3630

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