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			<p class="Type-of-Article" lang="en-GB">&nbsp;</p>
			<p class="Type-of-Article" lang="en-GB"><span class="CharOverride-1">Review Article</span></p>
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		<div class="Basic-Text-Frame">
			<p class="title- ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="title- ParaOverride-1" lang="en-GB">Multifunctional DRB3, a MHC Class II Gene, as a Useful Biomarker in Small Ruminants: A Review</p>
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			<p class="Authors ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Authors ParaOverride-1" lang="en-GB"><span class="CharOverride-2" lang="en-US">Hira Paracha</span><span class="CharOverride-3" lang="en-US">1</span><span class="CharOverride-2" lang="en-US">, Tanveer Hussain</span><span class="CharOverride-3" lang="en-US">2</span><span class="CharOverride-2" lang="en-US">, Muhammad Zahid Tahir</span><span class="CharOverride-3" lang="en-US">3</span><span class="CharOverride-2" lang="en-US">, Atiya Yasmeen</span><span class="CharOverride-3" lang="en-US">2</span><span class="CharOverride-2" lang="en-US">, Muhammad Tariq Pervez</span><span class="CharOverride-3" lang="en-US">1</span><span class="CharOverride-2" lang="en-US">, Ali Ahmad Sheikh</span><span class="CharOverride-3" lang="en-US">4</span><span class="CharOverride-2" lang="en-US">, Abbas Haider</span><span class="CharOverride-3" lang="en-US">5</span><span class="CharOverride-2" lang="en-US">, Rizwan Ali</span><span class="CharOverride-3" lang="en-US">2</span><span class="CharOverride-2" lang="en-US">, Waqas Ahmad Khan</span><span class="CharOverride-3" lang="en-US">6</span><span class="CharOverride-2" lang="en-US"> </span><span class="CharOverride-2">   </span></p>
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			<p class="Normal ParaOverride-2"><span class="CharOverride-5">1</span><span class="CharOverride-6">Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000; </span><span class="CharOverride-5">2</span><span class="CharOverride-6">Virtual University of Pakistan, Lahore; </span><span class="CharOverride-5">3</span><span class="CharOverride-6">Department of Theriogenology, University of Veterinary and Animal Sciences, Lahore, 54000; </span><span class="CharOverride-5">4</span><span class="CharOverride-6">University Diagnostic Lab, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.; </span><span class="CharOverride-5">5</span><span class="CharOverride-6">Livestock and Dairy Development Department, Punjab, Pakistan; </span><span class="CharOverride-5">6</span><span class="CharOverride-6">University of Sargodha, Pakistan.</span></p>
		</div>
		<div>
			<p class="Abstract ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Abstract ParaOverride-1" lang="en-GB"><span class="CharOverride-8">Abstract</span> | Major histocompatibility complex (MHC) is a large family of genes present in various vertebrates and is well known for the diversity of its alleles. These genes play an important role in the recognition of foreign antigens and mediating an immune response. MHC is classified as Class I, II and III molecules based on their molecular weights as well as differences in their cellular distribution and function. DRB3 gene is a member of MHC Class II and is known to show extensive polymorphism. This gene is being used as marker in phylogenetic and molecular genetics. This paper is aimed to review the role of DRB3 gene in goats.</p>
		  <p class="Abstract ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Abstract ParaOverride-1" lang="en-GB"><span class="CharOverride-8">Keywords</span> | MHC, DRB3, Polymorphism, Immune response, Ruminants to maintain a sustainable dairy industry in the future</p>
		  <p class="Abstract ParaOverride-1" lang="en-GB">&nbsp;</p>
		</div>
		<div class="Basic-Text-Frame">
			<p class="Editor----Citation" lang="en-GB"><span class="CharOverride-9">Editor</span> | Tahir Yaqub, University of Veterinary and Animal Sciences, Lahore, Pakistan.</p>
			<p class="Editor----Citation" lang="en-GB"><span class="CharOverride-8">Received</span> | October 08, 2014; <span class="CharOverride-8">Revised</span> | November 05, 2014; <span class="CharOverride-8">Accepted</span> | November 07, 2014; <span class="CharOverride-8">Published</span> | January 10, 2015&#9;&#9;</p>
			<p class="Editor----Citation" lang="en-GB"><span class="CharOverride-8">Contribution</span> | Hira Paracha and Tanveer Hussain contributed equally as first author.</p>
			<p class="Editor----Citation" lang="en-GB"><span class="CharOverride-8">*Correspondence</span> | Tanveer Hussain, Virtual University of Pakistan, Lahore; <span class="CharOverride-8">Email:</span> tanveer.hussain@vu.edu.pk</p>
			<p class="Editor----Citation" lang="en-GB"><span class="CharOverride-8">Citation</span> | Paracha H, Hussain T, Tahir MZ, Yasmeen A, Pervez MT, Sheikh AA, Haider A, Ali R, Khan WA (2015). Multifunctional DRB3, a MHC class II gene, as a useful biomarker in small ruminants: a review. J. Inf. Mol. Biol. 3 (1): 19-23.</p>
			<p class="Editor----Citation" lang="en-GB"><span class="CharOverride-9">DOI</span> | <a href="http://dx.doi.org/10.14737/journal.jimb/2015/3.1.19.23"><span class="Hyperlink">http://dx.doi.org/10.14737/journal.jimb/2015/3.1.19.23</span></a></p>
			<p class="Editor----Citation" lang="en-GB"><span class="CharOverride-9">I</span><span class="CharOverride-8">SSN (Online)</span> |  2307-5465; <span class="CharOverride-8">ISSN (Print)</span>  | 2307-5716</p>
			<p class="Editor----Citation" lang="en-GB"><span class="CharOverride-9">Copyright </span>© 2015 Paracha et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
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			<p class="Heading-1--Introduction----" lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" lang="en-GB">&nbsp;</p>
		  <p class="Heading-1--Introduction----" lang="en-GB">INTRODUCTION</p>
			<p class="Caps-on-First-Para ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Caps-on-First-Para ParaOverride-1" lang="en-GB"><span class="_idGenDropcap-1">P</span>athogens are one of the major extermination agents reported to date (<a href="#Radwan-J--Biedrzycka-A--Babik-W--2010-."><span class="Hyperlink">Radwan et al., 2010</span></a>). Meanwhile, the decrease in genetic diversity among populations makes them more vulnerable to pathogen attack. This argument relates to the polymorphic genes of major histocompatibility complex (MHC) which initiate the adaptive immune response by encoding proteins and presents pathogen derived antigens to T cells. Although some other polymorphic genes also show effective response against pathogenic assaults but MHC genes play a primary role in immune response as compared to other polymorphic genes (<a href="#Radwan-J--Biedrzycka-A--Babik-W--2010-."><span class="Hyperlink">Radwan et al., 2010</span></a>).</p>
		  <p class="Caps-on-First-Para ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Normal ParaOverride-3"><span class="CharOverride-12">According to the Red Queen Hypothesis, the immune defense of an organism have to face the evolving pathogens constantly, hence the genetic diversity was developed in MHC in order to cope with this race for domination (</span><a href="#Gowane-GR--Vandre-RK--Maya-N--Sharma-AK--2013-"><span class="Hyperlink CharOverride-13">Gowane et al., 2013</span></a><span class="CharOverride-12">). MHC is a group of closely linked genes which forms an important genetic component of the mammalian immune system. This group of cell surface glycoproteins plays an important role in the recognition of foreign peptide antigens (</span><a href="#Radwan-J--Biedrzycka-A--Babik-W--2010-."><span class="Hyperlink CharOverride-13" lang="en-GB">Radwan et al., 2010</span></a><span class="CharOverride-12">). MHC is classified into <span class="Body-Text ParaOverride-1"><span lang="en-US">three main classes as I, II and III based on differences in their functions. The general structure of MHC is </span>conserved in mammalian species although some regions in mammals are more conserved and some are less (<a href="#Sheikhmohammadi-R--Hashemi-A--Mardani-K--2010-."><span class="Hyperlink">Sheikhmohammadi et al., 2010</span></a>). MHC Class I molecules are found on almost all cells and exhibit proteins to cytotoxic T cells while molecules of MHC Class II reside on specific immune cells, particularly on some antigen presenting cells (APCs) like macrophages and B cells (<a href="#Figure-1"><span class="Hyperlink">Figure 1</span></a>)(<a href="#Dukkipati-VSR--Blair-HT--Garrick-DJ--Murray-A--2006"><span class="Hyperlink">Dukkipati et al., 2006</span></a>).</span></span></p>
			<p class="Normal ParaOverride-3">&nbsp;</p>
			
          <div class="pt" > <a href="http://nexusacademicpublishers.com/uploads/figures/20150116225001.png" target="new"><img class="img_display" src="http://nexusacademicpublishers.com/uploads/figures/20150116225001.png" width="80" height="80"></a>
            
            <p class="Figure--and-Table-Heading" lang="en-GB"><span class="CharOverride-8"><a id="Figure-1"></a>Figure 1:</span><span class="CharOverride-14"> </span><span class="CharOverride-15"><a href="http://nexusacademicpublishers.com/uploads/figures/20150116225001.png">α and <span class="CharOverride-15">β </span>polypeptide chains of MHC class II molecule, (www.mcb.uct.ac.za)</a></p>
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			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
		  <p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
		  <p class="Heading-1--Introduction----" lang="en-GB">STRUCTURE AND FUNCTION OF DRB3 GENE</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">Molecules of Class II are heterodimer glycoproteins consisting of two polypeptide chains (<span class="CharOverride-15">α</span> and <span class="CharOverride-15">β</span>). Under the DR region of the MHC complex, highly polymorphic <span class="CharOverride-15">β</span> chain encoded by DRB genes is found (<a href="#Zhao-Y--Xu-H--Shi-L--Zhang-J--2011-."><span class="Hyperlink">Zhao et al., 2011</span></a>). DRA gene encodes<span class="CharOverride-15"> α</span> chain whereas <span class="CharOverride-15">β</span> chain is coded by DRB gene (<a href="#Naskar-S--Deb-SM--Niranjan-SK--Kumar-S--Sharma-D--Sakaram-D--Sharma-A--2012-"><span class="Hyperlink">Naskar et al., 2012</span></a>)<span class="CharOverride-8">. </span>Three BoLA (bovine leukocyte antigen) DRB genes (DRB1, 2 and 3) are reported in bovines but only DRB3 is functional (<a href="#Singh-PK--Singh-SV--Singh-MK--Saxena-VK--Singh-AV--Sohal-JS--2012-"><span class="Hyperlink">Singh et al., 2012</span></a>). DRB1 is a pseudogene, DRB2 is expressed at lower level and DRB3 gene is highly expressed and polymorphic (<a href="#Wei-K--Zhang-Z--Wang-X--Zhang-W--Xu-X--Shen-F-and-Yue-B--2010-."><span class="Hyperlink">Wei et al., 2010</span></a>). DRB3 being a member of MHC class II genes and being polymorphic, plays significant role in disease resistance and in immune responsiveness variability (<a href="#Radwan-J--Biedrzycka-A--Babik-W--2010-."><span class="Hyperlink">Radwan et al., 2010</span></a>).</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
		  <p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" lang="en-GB">POLYMORPHIC NATURE OF DRB3 GENE</p>
		  <p class="Heading-1--Introduction----" lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">There are a large number of MHC genes and their alleles are present in most of the vertebrates. Class I play role in the recognition and binding of intracellular antigens while Class II genes are analogous to extracellular antigens (<a href="#Singh-PK--Singh-SV--Singh-MK--Saxena-VK--Singh-AV--Sohal-JS--2012-"><span class="Hyperlink">Singh et al., 2012</span></a>). In higher vertebrates these polymorphic genes are grouped together and these have important role in lymphocyte mediated immune surveillance (<a href="#Wei-K--Zhang-Z--Wang-X--Zhang-W--Xu-X--Shen-F-and-Yue-B--2010-."><span class="Hyperlink">Wei et al., 2010</span></a>). Class II genes are highly polymorphic and this polymorphism is due to the large number of amino acids among alleles at each locus (<a href="#Yakubu-A--Salako-AE--De-Donato"><span class="Hyperlink">Yakubu et al., 2013</span></a>). The defective expression of Class II has been characterized as a disease of severe immunodeficiency called bare lymphocyte syndrome (<a href="#Li-MH--Li-K--Kantanen-J--Feng-Z--Fan-B--Zhao-SH--2006-."><span class="Hyperlink">Li et al., 2006</span></a>). DRB3 is the most polymorphic class II gene in cattle and closely linked with DQ, hence DRB3 diversity is considered the diversity of entire class IIa. This polymorphism of MHC Class I and II genes is of great interest for evolutionary biologists and this genetic polymorphism is reported in various vertebrate species (<a href="#Radwan-J--Biedrzycka-A--Babik-W--2010-."><span class="Hyperlink">Radwan et al., 2010</span></a>).</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
		  <p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" lang="en-GB">SUBTYPES DRA AND DRB IN MHC RESTRICTED IMMUNE RESPONSE</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">In the literature, not much has been reported on caprine MHC Class II. The bovine DR and DQ are two antigens of MHC Class II and are similar to the MHC of goats named Caprine lymphocyte antigen (CLA) or goat lymphocyte antigen (GOLA). Principle Class II proteins are present on the surface of goat cells and MHC molecules of subtype DR have been recognized as member of this class. At present, two DRB loci have been identified (<a href="#Radwan-J--Kawalko-A--W-jcik-JM--Babik-W--2007"><span class="Hyperlink">Radwan et al., 2007</span></a>). In sheep and cattle, the MHC II genes have been largely identified while in goats only DRA and DRB genes have been sequenced. It is cleared from cytogenetic and physical mapping that Caprine MHC resides on chromosome 23 and its structural organization is same as of ovine and bovine orthologous regions (<a href="#Baghizadeh-A--Bahaaddini-M--Mohamadabadi-MR--Askari-N--2009-."><span class="Hyperlink">Baghizadeh et al., 2009</span></a>). Among various types of MHC class II, the DQ and DR subtypes are polymorphic in human and other domestic species. These subtypes probably play a major role in the development of MHC restricted immune responses. It has been reported that there are 22 different alleles for one DRB gene in goat, but some experimental data demonstrates that there exists a second Caprine DRB locus (<a href="#Amills-M--Sulas-C--S-nchez-A--Bertoni-G--Zanoni-R--Obexer-Ruff-G--2004"><span class="Hyperlink">Amills et al., 2004</span></a>). The MHC has been related to a wide variety of production traits in domestic animals. It has been examined for fertility, growth, milk and milk fat yields in cattle, chickens and swine where these factors are associated with the MHC and have developed some enhanced economic benefits. There are many genes in MHC which have a huge variety of functions but are not related to the immune response (<a href="#Amills-M--Francino-O--S-anchez-A--1996-."><span class="Hyperlink">Amills et al., 1996</span></a>).</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
		  <p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" lang="en-GB">DRB3 GENE AS AN INFORMATIVE MARKER</p>
		  <p class="Heading-1--Introduction----" lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">The proteins that are important for the functioning of immune system are encoded by MHC (<a href="#Othman-OE--Ahmad-S--2010-"><span class="Hyperlink">Othman and Ahmad, 2010</span></a>). DRB locus is the most polymorphic among the MHC genes (<a href="#Maillard-JC--Martinez-D--Bensaidc-A--1996-"><span class="Hyperlink">Maillard et al., 1996</span></a>). The DRB3 locus exists in the antigen presenting site and any variability in this region may lead to variability in the immune responsiveness of different individuals to particular pathogens. Due to this reason, the importance of the study of polymorphism of this locus has increased (<a href="#Bot-J--Karlsson-LJE--Greef-J--Witt-C--2004-."><span class="Hyperlink">Bot et al., 2004</span></a>). The MHC has been acknowledged to regulate the progression of many infectious diseases, so it is implied that development of markers for these loci may prove helpful in pinpointing superior haplotypes for disease resistance on the condition that association between the trait and these markers can be established. The upstream regulatory region (URR) of the DRB3 gene lies approximately 200 bp upstream of the transcriptional start site and it has strong promoter/enhancer activity. This URR of the DRB3 gene consists of a series of sequence motifs like W, X, Y, CCAAT and TATA boxes. Since these motifs are highly conserved to all MHC Class II genes, their positions as well as spacing are crucial for precise transcription of BoLA genes (<a href="#Behl-JD--Verma-NK--Tyagi-N--Mishra-P--Behl-R--Joshi-BK--2012-."><span class="Hyperlink">Behl et al., 2012</span></a>). DRB3 exon 2 is highly polymorphic with &gt;100 identified alleles (<a href="#Kumar-S--Sangwan-ML--Ahlawat-S--Barwar-A--2011-."><span class="Hyperlink">Kumar et al., 2011</span></a>) and encode the antigen recognition site of the DR (<a href="#Schwab-AE--Geary-TG--Baillargeon-P--Schwab-AJ--Fecteau-G--2009-."><span class="Hyperlink">Schwab et al., 2009</span></a>). The ability of DRB3 to exhibit high polymorphism makes it a strong candidate to be used as a marker in molecular genetics and phylogenetic studies (<a href="#Untalan-PM--Pruett-JH--Steelman-CD--2007-."><span class="Hyperlink">Untalan et al., 2007</span></a>). </p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
		  <p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" lang="en-GB">DISCUSSION</p>
		  <p class="Heading-1--Introduction----" lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">The polymorphism of MHC occurs at the residues that are involved in binding of peptides and this polymorphism is maintained by some balanced selection. This variability of MHC will be helpful for evolutionary biologists and this diversity level will be expected to connect survival and welfare of a population (<a href="#Bao-P--Yan-P--Liang-C--Guo-X--Pei-J--Chu-M--ZhuX--2012-"><span class="Hyperlink">Bao et al., 2012</span></a>). There are various forces that result the population of a gene pool. Among these forces evolutionary processes caused by adaptation to environmental factors are of great importance. In the most polymorphic regions such as MHC, the influence of these forces can be analysed by using markers. MHC genes are variable in vertebrates and play a significant role in immune response and antigen presentation (<a href="#Takeshima-S--Saitou-N--Morita-M--Inoko-H--Aida-Y--2003-"><span class="Hyperlink">Takeshima et al., 2003</span></a>). Nowadays certain advances have been made to improve animal stocks through selective breeding. The previous techniques of selection rely on subjective assessment of phenotype and progeny testing programs. These are time consuming and laborious. New techniques are being developed for the identification and isolation of DNA markers which are associated with the genes of disease resistance and economically important production traits. These markers will provide an objective system to animal breeders for the identification at the time of birth or even earlier, animals carrying desired genes (<a href="#Bozkaya-F--Kuss-AW--Geldermann-H--2007-."><span class="Hyperlink">Bozkaya et al., 2007</span></a>). Genetic variation is associated with resistance to pathogens. There is a chance to assess genetic variation associated with adaptive selection directly by studying genetic markers within MHC (<a href="#Gogolin-Ewens-KJ--Meeusen-ENT--Scott-PC--Adams-TE--Brandon-MR--1990-."><span class="Hyperlink">Gogolin-Ewens et al., 1990</span></a>). Due to the depletion of variation and inbreeding depression in the immunity genes makes populations more endangered to pathogens. In case of conservation efforts, variations in MHC molecules are significant. MHC presents pathogen derived antigens to the effector cells and hence they activate adaptive immune response (<a href="#Castillo-S--Srithayakumar-V--Meunier-V--Kyle-CJ--2010-."><span class="Hyperlink">Castillo et al., 2010</span></a>). Disease can be controlled by applying different approaches either to identify chromosomal regions or by identifying those genes that show response to vaccination. Identification of polymorphism requires large number of animals with associated genotypes and phenotypes. So, there is a requirement of certain genetic approaches such as whole genome scans using markers for the investigation of genes under complex traits or candidate genes derived from knowledge related to cellular pathways leading to pathology (<a href="#Glass-EJ--Baxter-R--Leach-RJ--Jann-OC--2012-."><span class="Hyperlink">Glass et al., 2012</span></a>). It would be interesting to improve disease resistance by genetic means in livestock production. To select immunological marker traits is an efficient tool for the improvement of disease resistance (<a href="#Eide-DM--Adnoy-T--Klemetsdal-G--Nesse-LL-Larsen-HJ--1991-."><span class="Hyperlink">Eide et al., 1991</span></a>).</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
		  <p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" lang="en-GB">FUTURE PROSPECTS</p>
		  <p class="Heading-1--Introduction----" lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">DRB3 gene, as a biomarker, could be used for gene assisted selection (GAS) or marker assisted selection (MAS) for the selection of safety traits and product quality. Moreover, MHC polymorphism could be used as a beneficial aid in the recognition of various pathogens.</p>
			<p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
		  <p class="Body-Text ParaOverride-1" lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" lang="en-GB">REFERENCES</p>
		  <p class="Heading-1--Introduction----" lang="en-GB">&nbsp;</p>
			
			  <li class="References ParaOverride-4"><a id="Amills-M--Francino-O--S-anchez-A--1996-."></a>Amills M, Francino O, S’anchez A (1996). A PCR-RFLP typing method for the caprine MHC class II DRB gene. Vet. Immunol. Immunop. 55(1): 255-260. <a href="http://dx.doi.org/10.1016/S0165-2427(96)05713-3"><span class="Hyperlink">http://dx.doi.org/10.1016/S0165-2427(96)05713-3</span></a></li>
				<li class="References ParaOverride-4"><a id="Amills-M--Sulas-C--S-nchez-A--Bertoni-G--Zanoni-R--Obexer-Ruff-G--2004"></a>Amills M, Sulas C, Sànchez A, Bertoni G, Zanoni R, Obexer-Ruff G (2004). Structural characterizationof the caprine major histocompatibility complex class II DQB1 (Cahi-DQB1) gene. Mol. Immunol. 44(9): 843-846. <a href="http://dx.doi.org/10.1016/j.molimm.2004.05.002"><span class="Hyperlink">http://dx.doi.org/10.1016/j.molimm.2004.05.002</span></a> PMid:15261455</li>
				<li class="References ParaOverride-4"><a id="Baghizadeh-A--Bahaaddini-M--Mohamadabadi-MR--Askari-N--2009-."></a>Baghizadeh A, Bahaaddini M, Mohamadabadi MR, Askari N (2009). Allelic Variations in Exon 2 of Caprine MHC Class II DRB3 Gene in Raeini Cashmere Goat. American-Eurasian J. Agri. Environ. Sci. 6(1): 454-459.</li>
				<li class="References ParaOverride-4"><a id="Bao-P--Yan-P--Liang-C--Guo-X--Pei-J--Chu-M--ZhuX--2012-"></a>Bao P, Yan P, Liang C, Guo X, Pei J, Chu M, ZhuX (2012). Genetic diversity analysis of DRB3.2 in domestic yak (Bos grunniens) in Qinghai-Tibetan Plateau. Afr. J. Biotechnol. 11(87): 15272-15279.</li>
				<li class="References ParaOverride-4"><a id="Behl-JD--Verma-NK--Tyagi-N--Mishra-P--Behl-R--Joshi-BK--2012-."></a>Behl JD, Verma NK, Tyagi N, Mishra P, Behl R, Joshi BK (2012). The Major Histocompatibility Complex in Bovines: A Review. ISRN. Vet. Sci. 872710. PMid:23738132 PMCid:PMC3658703</li>
				<li class="References ParaOverride-4"><a id="Bot-J--Karlsson-LJE--Greef-J--Witt-C--2004-."></a>Bot J, Karlsson LJE, Greef J, Witt C (2004). Association of the MHC with production traits in Merino ewes. Livest. Prod. Sci. 86(1): 85-91. <a href="http://dx.doi.org/10.1016/S0301-6226(03)00146-5"><span class="Hyperlink">http://dx.doi.org/10.1016/S0301-6226(03)00146-5</span></a></li>
				<li class="References ParaOverride-4"><a id="Bozkaya-F--Kuss-AW--Geldermann-H--2007-."></a>Bozkaya F, Kuss AW, Geldermann H (2007). DNA variants of the MHC show location-specific convergence between sheep, goat and cattle. Small Ruminant Res. 70(2): 174-182. <a href="http://dx.doi.org/10.1016/j.smallrumres.2006.03.001"><span class="Hyperlink">http://dx.doi.org/10.1016/j.smallrumres.2006.03.001</span></a></li>
				<li class="References ParaOverride-4"><a id="Castillo-S--Srithayakumar-V--Meunier-V--Kyle-CJ--2010-."></a>Castillo S, Srithayakumar V, Meunier V, Kyle CJ (2010). Characterization of Major Histocompatibility Complex (MHC) DRB Exon 2 and DRA Exon 3 Fragments in a Primary Terrestrial Rabies Vector (Procyon lotor). PLoS ONE. 5(8): e12066. <a href="http://dx.doi.org/10.1371/journal.pone.0012066"><span class="Hyperlink">http://dx.doi.org/10.1371/journal.pone.0012066</span></a> PMid:20706587 PMCid:PMC2919397</li>
				<li class="References ParaOverride-4"><a id="Dukkipati-VSR--Blair-HT--Garrick-DJ--Murray-A--2006"></a>Dukkipati VSR, Blair HT, Garrick DJ, Murray A (2006). Ovar-Mhc’- ovine major histocompatibility complex: structure and gene polymorphisms. Genet. Mol. Res. 5(4): 581-608. PMid:17183471</li>
				<li class="References ParaOverride-4"><a id="Eide-DM--Adnoy-T--Klemetsdal-G--Nesse-LL-Larsen-HJ--1991-."></a>Eide DM, Adnoy T, Klemetsdal G, Nesse LL,Larsen HJ (1991). Selection for immune response in goats: the antibody response to diphtheria toxoid after 12 years of selection. J. Anim. Sci. 69: 3967-3976. PMid:1778809</li>
				<li class="References ParaOverride-4"><a id="Glass-EJ--Baxter-R--Leach-RJ--Jann-OC--2012-."></a>Glass EJ, Baxter R, Leach RJ, Jann OC (2012). Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle. Vet. Immunol. Immunop. 148(1): 90-99. <a href="http://dx.doi.org/10.1016/j.vetimm.2011.05.009"><span class="Hyperlink">http://dx.doi.org/10.1016/j.vetimm.2011.05.009</span></a> PMid:21621277 PMCid:PMC3413884</li>
				<li class="References ParaOverride-4"><a id="Gogolin-Ewens-KJ--Meeusen-ENT--Scott-PC--Adams-TE--Brandon-MR--1990-."></a>Gogolin-Ewens KJ, Meeusen ENT, Scott PC, Adams TE, Brandon MR (1990). Genetic selection for disease resistance and traits of economic importance in animal production. Rev. Sci. Tech. Off. Int. Epiz 9(3): 865-896.</li>
				<li class="References ParaOverride-4"><a id="Gowane-GR--Vandre-RK--Maya-N--Sharma-AK--2013-"></a>Gowane GR, Vandre RK, Maya N, Sharma AK (2013). Major histocompatibility complex (MHC) of bovines: an insight into infectious disease resistance. Livest. Res. Int. 1(1): 46-57.</li>
				<li class="References ParaOverride-4"><a id="Kumar-S--Sangwan-ML--Ahlawat-S--Barwar-A--2011-."></a>Kumar S, Sangwan ML, Ahlawat S, Barwar A (2011). Polymorphism in DRB3 exon 2 by PCR-RFLP and its association with mastitis in Murrah baffaloes. Ind. J. Biotech. 10: 232-234.</li>
				<li class="References ParaOverride-4"><a id="Li-MH--Li-K--Kantanen-J--Feng-Z--Fan-B--Zhao-SH--2006-."></a>Li MH, Li K, Kantanen J, Feng Z, Fan B, Zhao SH (2006). Allelic variations in exon 2 of caprine MHC class II DRB3 gene in Chinese indigenous goats. Small Ruminant Res. 66(1): 236-243. <a href="http://dx.doi.org/10.1016/j.smallrumres.2005.09.017"><span class="Hyperlink">http://dx.doi.org/10.1016/j.smallrumres.2005.09.017</span></a></li>
				<li class="References ParaOverride-4"><a id="Maillard-JC--Martinez-D--Bensaidc-A--1996-"></a>Maillard JC, Martinez D, Bensaidc A (1996). An Amino Acid Sequence Coded by the Exon 2 of the BoLA DRB3 Gene Associated with a BoLA Class I Specificity Constitutes a Likely Genetic Marker of Resistance to Dermatophilosis in Brahman Zebu Cattle of Martinique (FWI). Ann. N. Y. Acad. Sci. 791(1): 185-197. <a href="http://dx.doi.org/10.1111/j.1749-6632.1996.tb53525.x"><span class="Hyperlink">http://dx.doi.org/10.1111/j.1749-6632.1996.tb53525.x</span></a> PMid:8784500</li>
				<li class="References ParaOverride-4"><a id="Singh-PK--Singh-SV--Singh-MK--Saxena-VK--Singh-AV--Sohal-JS--2012-"></a>Singh PK, Singh SV, Singh MK, Saxena VK, Singh AV, Sohal JS (2012). Genetic Analysis of MHC Class II DRB gene in an endangered jamunapari breed of goats. Ind. J. Biotechnol. 11(2): 220-223.</li>
				<li class="References ParaOverride-4"><a id="Naskar-S--Deb-SM--Niranjan-SK--Kumar-S--Sharma-D--Sakaram-D--Sharma-A--2012-"></a>Naskar S, Deb SM, Niranjan SK, Kumar S, Sharma D, Sakaram D, Sharma A (2012). Molecular characterization of MHC-DRB cDNA in water buffalo (Bubalus bubalis). Genet. Mol. Biol. 35(1): 95-98. <a href="http://dx.doi.org/10.1590/S1415-47572012005000013"><span class="Hyperlink">http://dx.doi.org/10.1590/S1415-47572012005000013</span></a> PMid:22481880 PMCid:PMC3313522</li>
				<li class="References ParaOverride-4"><a id="Othman-OE--Ahmad-S--2010-"></a>Othman OE, Ahmad S (2010). Genetic Polymorphism of BoLA - DRB3 Exon 2 in Egyptian Buffalo. Genes, Genomes and Genomics. 4(1): 70-73.</li>
				<li class="References ParaOverride-4"><a id="Radwan-J--Kawalko-A--W-jcik-JM--Babik-W--2007"></a>Radwan J, Kawalko A, Wójcik JM, Babik W (2007). MHC-DRB3 variation in a free-living population of the European bison, Bison bonasus. Mol. Ecol. 16(3): 531-540. <a href="http://dx.doi.org/10.1111/j.1365-294X.2006.03179.x"><span class="Hyperlink">http://dx.doi.org/10.1111/j.1365-294X.2006.03179.x</span></a> PMid:17257111</li>
				<li class="References ParaOverride-4"><a id="Radwan-J--Biedrzycka-A--Babik-W--2010-."></a>Radwan J, Biedrzycka A, Babik W (2010). Does reduced MHC diversity decrease viability of vertebrate populations?. Bio. Conserv. 143(3): 537-544. <a href="http://dx.doi.org/10.1016/j.biocon.2009.07.026"><span class="Hyperlink">http://dx.doi.org/10.1016/j.biocon.2009.07.026</span></a></li>
				<li class="References ParaOverride-4"><a id="Schwab-AE--Geary-TG--Baillargeon-P--Schwab-AJ--Fecteau-G--2009-."></a>Schwab AE, Geary TG, Baillargeon P, Schwab AJ, Fecteau G (2009). Association of BoLA DRB3 and DQA1 alleles with susceptibly to Neospora caninum and reproductive outcome in Quebec Holstein cattle. Vet. Parasitol. 165(1): 136-140. <a href="http://dx.doi.org/10.1016/j.vetpar.2009.07.004"><span class="Hyperlink">http://dx.doi.org/10.1016/j.vetpar.2009.07.004</span></a> PMid:19646818</li>
				<li class="References ParaOverride-4"><a id="Sheikhmohammadi-R--Hashemi-A--Mardani-K--2010-."></a>Sheikhmohammadi R, Hashemi A, Mardani K (2010). Analysis of polymorphism of MHC class II BuLA DRB3 exon 2 gene in North West Iranian populations of theWater buffalo (<span class="CharOverride-17">Bubalus bubalis</span>) through PCR-SSCP. Int. J. Vet. Res. 4(4): 265-268.</li>
				<li class="References ParaOverride-4"><a id="Takeshima-S--Saitou-N--Morita-M--Inoko-H--Aida-Y--2003-"></a>Takeshima S, Saitou N, Morita M, Inoko H, Aida Y (2003). The diversity of bovine MHC class II DRB3 genes in Japanese Black, Japanese Shorthorn, Jersey and Holstein cattle in Japan. Gene. 316: 111-118. <a href="http://dx.doi.org/10.1016/S0378-1119(03)00744-3"><span class="Hyperlink">http://dx.doi.org/10.1016/S0378-1119(03)00744-3</span></a></li>
				<li class="References ParaOverride-4"><a id="Untalan-PM--Pruett-JH--Steelman-CD--2007-."></a>Untalan PM, Pruett JH, Steelman CD (2007). Association of the bovine leukocyte antigen major histocompatibility complex class II DRB3*4401 allele with host resistance to the Lone Star tick, Amblyomma americanum. Vet. Parasitol. 145(1): 190-195. <a href="http://dx.doi.org/10.1016/j.vetpar.2006.12.003"><span class="Hyperlink">http://dx.doi.org/10.1016/j.vetpar.2006.12.003</span></a> PMid:17208379</li>
				<li class="References ParaOverride-4"><a id="Wei-K--Zhang-Z--Wang-X--Zhang-W--Xu-X--Shen-F-and-Yue-B--2010-."></a>Wei K, Zhang Z, Wang X, Zhang W, Xu X, Shen F and Yue B (2010). Lineage pattern, trans-species polymorphism, and selection pressure among the major lineages of feline Mhc-DRB peptide-binding region. Immunogenetics. 62(5): 307- 317. <a href="http://dx.doi.org/10.1007/s00251-010-0440-5"><span class="Hyperlink">http://dx.doi.org/10.1007/s00251-010-0440-5</span></a> PMid:20372886</li>
		  <li class="References ParaOverride-4"><a id="Yakubu-A--Salako-AE--De-Donato"></a>Yakubu A, Salako AE, De Donato M, Takeet MI, Peters SO, Adefenwa MA, Okpeku M, Wheto M, Agaviezor BO, Sanni TM, Ajayi OO, Onasanya GO, Ekundayo OJ, Ilori BM, Amusan SA, Imumorin IG (2013). Genetic Diversity in Exon 2 of the Major Histocompatibility Complex Class II DQB1 Locus in Nigerian Goats. Biochem. Genet. 51(11-12): 954-966. <a href="http://dx.doi.org/10.1007/s10528-013-9620-y"><span class="Hyperlink">http://dx.doi.org/10.1007/s10528-013-9620-y</span></a> PMid:23835918</li>
				<li class="References ParaOverride-4"><a id="Zhao-Y--Xu-H--Shi-L--Zhang-J--2011-."></a>Zhao Y, Xu H, Shi L, Zhang J (2011). Polymorphisms in Exon 2 of MHC Class II DRB3 Gene of 10 Domestic Goats in Southwest China. Asian-Aust. J. Anim. Sci. 24(6): 752-756.</li>
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