Sironen et al. BMC Genomics 2010, 11:699 http://www.biomedcentral.com/1471-2164/11/699 software package Plink [40]. Haplotypes, the linkage dise- quilibrium plot and the Manhattan plot were produced with Haploview [41]. Additional material Additional file 1: The KAD associated region in the Finnish Yorkshire pig localized on porcine chromosome 15. The KAD associated homozygous region in the Finnish Yorkshire was identified in chromosome 15 between base pairs 93723216 and 94155055. A promising candidate gene Ubiquitin-protein ligase E3 (HECW2) is located within this region at the same position as two markers with lowest P-values (highlighted by circles). Another gene STK17b was also located within the homozygous region; however the known function of this gene in apoptosis would not infer a role for STK17b in KAD. Acknowledgements Funding for this study was provided by the Finnish Ministry of Agriculture and Forestry (Makera). The assistance of Tiina Jaakkola and Tarja Hovivuori in DNA extraction and Päivi Lahermo (Institute for Molecular Medicine Finland, FIMM) in genotyping with PorcineSNP60 Genotyping BeadChip (Illumina) is greatly appreciated. Author details 1Agrifood Research Finland, MTT, Biotechnology and Food Research, Genomics, FI-36100 Jokioinen, Finland. 2University of Pannonia, Institute of Environmental Sciences, H-8200 Veszprem, Hungary. 3First Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary. 4University of Helsinki, Department of Clinical Veterinary Sciences, Helsinki, Finland. Authors’ contributions AS carried out the molecular genetics studies, sequence alignments and drafted the manuscript. PU performed the statistical analysis and participated in drafting the manuscript. SN participated in the microscopical studies and contributed to drafting of the manuscript (microscopical studies). SP carried out the microscopical studies. MA participated in the design and coordination of the study. JV participated in the design and helped to draft the manuscript. All authors read and approved the final manuscript. Received: 7 July 2010 Accepted: 9 December 2010 Published: 9 December 2010 References 1. Boyle CA, Khoury MJ, Katz DF, Annest JL, Kresnow MJ, DeStefano F, Schrader SM: The relation of computer-based measures of sperm morphology and motility to male infertility. Epidemiology 1992, 3(3):239-246. 2. Linford E, Glover FA, Bishop C, Stewart DL: The relationship between semen evaluation methods and fertility in the bull. J Reprod Fertil 1976, 47(2):283-291. 3. Wallace MS: Infertility in the male dog. Probl Vet Med 1992, 4(3):531-544. 4. Kimmins S, Kotaja N, Davidson I, Sassone-Corsi P: Testis-specific transcription mechanisms promoting male germ-cell differentiation. Reproduction 2004, 128(1):5-12. 5. Kimmins S, Sassone-Corsi P: Chromatin remodelling and epigenetic features of germ cells. Nature 2005, 434(7033):583-589. 6. Hogeveen KN, Sassone-Corsi P: Regulation of gene expression in post- meiotic male germ cells: CREM-signalling pathways and male fertility. Hum Fertil (Camb) 2006, 9(2):73-79. 7. Aitken RJ, Kerr L, Bolton V, Hargreave T: Analysis of sperm function in globozoospermia: implications for the mechanism of sperm-zona interaction. Fertil Steril 1990, 54(4):701-707. 8. Moretti E, Collodel G, Scapigliati G, Cosci I, Sartini B, Baccetti B: ’Round head’ sperm defect. Ultrastructural and meiotic segregation study. J Submicrosc Cytol Pathol 2005, 37(3-4):297-303. Page 7 of 8 9. Dam AH, Koscinski I, Kremer JA, Moutou C, Jaeger AS, Oudakker AR, Tournaye H, Charlet N, Lagier-Tourenne C, van Bokhoven H, Viville S: Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. Am J Hum Genet 2007, 81(4):813-820. 10. Hurtgen JP, Johnson LA: Fertility of stallions with abnormalities of the sperm acrosome. J Reprod Fertil Suppl 1982, 32:15-20. 11. Toyama Y, Itoh Y: Ultrastructural features and pathogenesis of knobbed spermatozoa in a boar. Am J Vet Res 1993, 54(5):743-749. 12. Soderquist L: Reduced fertility after artificial insemination in a ram with a high incidence of knobbed acrosomes. Vet Rec 1998, 143(8):227-228. 13. Chenoweth PJ: Genetic sperm defects. Theriogenology 2005, 64(3):457-468. 14. Santos NR, Krekeler N, Schramme-Jossen A, Volkmann DH: The knobbed acrosome defect in four closely related dogs. Theriogenology 2006, 66(6-7):1626-1628. 15. Kopp C, Sironen A, Ijas R, Taponen J, Vilkki J, Sukura A, Andersson M: Infertile boars with knobbed and immotile short-tail sperm defects in the Finnish Yorkshire breed. Reprod Domest Anim 2008, 43(6):690-695. 16. Schill WB: Some disturbances of acrosomal development and function in human spermatozoa. Hum Reprod 1991, 6(7):969-978. 17. Blom E, Birch-Andersen A: The ultrastructure of a characteristic spermhead-defect in the boar: the SME-defect. Andrologia 1975, 7(3):199-209. 18. Andersen K, Filseth O: The occurrence of a “SME"-defect-like abnormality in the head of spermatozoa from a Norwegian Landrace boar. Nord Vet Med 1976, 28(10):511-514. 19. Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O: Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res 2000, 7(1):65-73. 20. Miyazaki K, Ozaki T, Kato C, Hanamoto T, Fujita T, Irino S, Watanabe K, Nakagawa T, Nakagawara A: A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances its transcriptional activity. Biochem Biophys Res Commun 2003, 308(1):106-113. 21. Haraguchi CM, Mabuchi T, Hirata S, Shoda T, Hoshi K, Yokota S: Ubiquitin signals in the developing acrosome during spermatogenesis of rat testis: an immunoelectron microscopic study. J Histochem Cytochem 2004, 52(11):1393-1403. 22. Chianese R, Scarpa D, Berruti G, Cobellis G, Pierantoni R, Fasano S, Meccariello R: Expression and localization of the deubiquitinating enzyme mUBPy in wobbler mouse testis during spermiogenesis. Gen Comp Endocrinol 2010, 166(2):289-95. 23. Sanjo H, Kawai T, Akira S: DRAKs, novel serine/threonine kinases related to death-associated protein kinase that trigger apoptosis. J Biol Chem 1998, 273(44):29066-29071. 24. Doherty GA, Byrne SM, Austin SC, Scully GM, Sadlier DM, Neilan TG, Kay EW, Murray FE, Fitzgerald DJ: Regulation of the apoptosis-inducing kinase DRAK2 by cyclooxygenase-2 in colorectal cancer. Br J Cancer 2009, 101(3):483-491. 25. Kuwahara H, Nakamura N, Kanazawa H: Nuclear localization of the serine/ threonine kinase DRAK2 is involved in UV-induced apoptosis. Biol Pharm Bull 2006, 29(2):225-233. 26. Sutovsky P: Ubiquitin-dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: killing three birds with one stone. Microsc Res Tech 2003, 61(1):88-102. 27. Yi YJ, Manandhar G, Sutovsky M, Li R, Jonakova V, Oko R, Park CS, Prather RS, Sutovsky P: Ubiquitin C-terminal hydrolase-activity is involved in sperm acrosomal function and anti-polyspermy defense during porcine fertilization. Biol Reprod 2007, 77(5):780-793. 28. Morales P, Kong M, Pizarro E, Pasten C: Participation of the sperm proteasome in human fertilization. Hum Reprod 2003, 18(5):1010-1017. 29. Sutovsky P, Manandhar G, McCauley TC, Caamano JN, Sutovsky M, Thompson WE, Day BN: Proteasomal interference prevents zona pellucida penetration and fertilization in mammals. Biol Reprod 2004, 71(5):1625-1637. 30. Morales P, Pizarro E, Kong M, Jara M: Extracellular localization of proteasomes in human sperm. Mol Reprod Dev 2004, 68(1):115-124. 31. Bialy LP, Ziemba HT, Marianowski P, Fracki S, Bury M, Wojcik C: Localization of a proteasomal antigen in human spermatozoa: immunohistochemical electron microscopic study. Folia Histochem Cytobiol 2001, 39(2):129-130. 32. Ziemba H, Bialy LP, Fracki S, Bablok L, Wojcik C: Proteasome localization and ultrastructure of spermatozoa from patients with