J.Dairy Sci.87:2442–2448©American Dairy Science Association,2004.Association of CXCR2Polymorphisms with Subclinical and Clinical Mastitis in Dairy CattleS.M.Youngerman,A.M.Saxton,S.P.Oliver,and G.M.PighettiDepartment of Animal Science,The University of Tennessee,Knoxville 37996ABSTRACTThe ability to identify objectively cows that are moreor less susceptible to mastitis has been a long-standinggoal.Genetic markers associated with inflammatoryresponses during mastitis could aid in selection ofthese cattle.One potential marker is CXCR2,a chemo-kine receptor required for neutrophil migration to in-fection sites,which contains single nucleotide poly-morphisms (SNP)within the gene.The objective of thisexperiment was to evaluate the association of CXCR2SNP genotypes with subclinical and clinical mastitis.Thirty-seven Holstein and 42Jersey cows that com-pleted at least 2full lactations were used.Quarterforemilk samples were collected for bacteriological ex-amination quarterly and when cows exhibited clinicalmastitis.Subclinical mastitis was defined as the pres-ence of the same pathogen in the same quarter in atleast 2of 3consecutive samples.A significant associa-tion was detected between CXCR2SNP +777genotypeand percentages of subclinical mastitis cases in Hol-steins.Holsteins expressing genotype GG had de-creased percentages of subclinical mastitis,but geno-type CC cows had increased percentages of subclinicalmastitis.Significant differences in clinical mastitis in-cidence were not detected between genotypes for eitherbreed.This approach of genetically identifying masti-tis resistant cows may represent an effective meansof marker-assisted selection for mastitis and other in-flammatory diseases involving neutrophils.(Key words:mastitis,single nucleotide polymor-phism,CXCR2,interleukin-8receptor)Abbreviation key:BTA =Bos taurus autosome,DES =Dairy Experiment Station,MTES =MiddleTennessee Experiment Station,SNP =single nucleo-tide polymorphism.INTRODUCTIONMastitis continues to be the most economically dev-astating disease affecting the dairy industry.Identifi-Received December 11,2003.Accepted April 2,2004.Corresponding author:G.M.Pighetti;e-mail:pighetti@utk.edu.2442cation of one or more genetic markers associated with mastitis susceptibility,resistance,or both would allow producers to decrease costs associated with mastitis by improving herd health through animal selection.Because mastitis and other infectious diseases are complex and use many different genes,it is highly probable that several genetic markers used in combi-nation would provide the best means for making ge-netic progress.Genes associated with immune re-sponses of the mammary gland are potential markers because of their importance in mastitis.Several stud-ies have identified polymorphic bovine genes responsi-ble for encoding the major histocompatability complex,cytokine and cytokine receptors,and natural resis-tance associated macrophage protein-1(Dietz et al.,1997;Grosse et al.,1999;Ables et al.,2002).However,only a few studies have associated major histocompa-tability complex alleles DRB3.2∗3,∗11,∗16,and ∗23with mastitis incidence or immune function (Dietz et al.,1997;Kelm et al.,1997;Sharif et al.,1998,2000;Park et al.,2004).Genes associated with neutrophil function are po-tential genetic markers for mastitis,as neutrophil mi-gration from blood to the site of infection is essential for resolution of most mastitis pathogens (Paape et al.,2000).The ability of neutrophils to migrate into infected tissues is dependent upon recognition of in-flammatory mediators by neutrophil cytokine,chemo-kine,and complement receptors (Burvenich et al.,1994).Two chemokine receptors present on neutrophil surfaces,CXCR1and CXCR2,are required for maxi-mum neutrophil function during infection (Murphy and Tiffany,1991).Recognition of chemokines by CXCR1and CXCR2induces neutrophil activation,chemotaxis,and eventual phagocytosis of pathogens (Peveri et al.,1988;Podolin et al.,2002).Both CXCR1and CXCR2are potential candidate genes for mastitis resistance;however,only the se-quence for bovine CXCR2mRNA is publicly available (GenBank Accession No.U19947).The bovine CXCR2gene has been mapped to BTA (Bos taurus autosome)2,approximately 90.3cM from the centromere.This region on BTA 2shares conserved synteny and gene order with both Homo sapien autosome 2and mouse
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