Sironen et al. BMC Genomics 2010, 11:699 http://www.biomedcentral.com/1471-2164/11/699 R E S E A R C H A R T I C L E Open Access Knobbed acrosome defect is associated with a region containing the genes STK17b and HECW2 on porcine chromosome 15 Anu Sironen1*, Pekka Uimari1, Szabolcs Nagy2, Sándor Paku3, Magnus Andersson4, Johanna Vilkki1 Abstract Background: Male infertility is an increasing problem in all domestic species including man. Localization and identification of genes involved in defects causing male infertility provide valuable information of specific events in sperm development. Correct condensation of the sperm head and development of the acrosome are required for fertile sperm. In the Finnish Yorkshire pig population a knobbed acrosome defect (KAD) has been reported which appears to be of genetic origin. In previous studies we have shown that a large number of affected spermatozoa have a cystic swelling anterior to the apical part of the acrosome. Results: Characterization of the knobbed acrosome affected sperm revealed that both the acrosomal granules and chromatin are affected. This type of KAD appears to be a previously unknown and serious form of the defect. A genome wide scan with PorcineSNP60 Genotyping BeadChip defined the KAD associated region within 0.7 Mbp on porcine chromosome 15. Two genes, STK17b and HECW2, located within this region were sequenced. The expression of these genes appeared comparable in KA-affected and control boars. The known function of HECW2 in acrosome development highlighted this gene as a good candidate responsible for the KAD. One nonsynonymous SNP was identified within the HECW2 gene. However, as this mutation was found in homozygous state in individuals with normal sperm, this is not likely to be the causal mutation. Conclusions: In this study we identified two candidate genes for a severe defect affecting both the sperm acrosome and chromatin that causes infertility. One of these genes, HECW2, plays an important role in ubiquitination, a prerequisite for chromatin remodelling and acrosome formation, highlighting the involvement of this gene in the knobbed acrosome defect and male infertility. Background Male infertility is becoming increasingly prevalent partly due to environmental factors, but many defects in sperm development arise from a genetic cause. Problems in the production and maturation of sperm are the most common causes of male infertility resulting in low sperm numbers, morphologically abnormal sperm or low sperm motility [1-3]. Despite efforts to reveal the genes and their functions in spermatogenesis, little is known about the underlying causes of male infertility. Therefore, the localization and identification of muta- tions specifically affecting spermatogenesis provide * Correspondence: anu.sironen@mtt.fi 1Agrifood Research Finland, MTT, Biotechnology and Food Research, Genomics, FI-36100 Jokioinen, Finland Full list of author information is available at the end of the article invaluable information for investigating the causes of male infertility. Mammalian spermatogenesis is a complex process, where diploid spermatogonia develop into haploid, highly specialized spermatozoa. Spermatogenesis includes many testis-specific processes that are controlled by complex regulatory mechanisms [4,5]. During spermiogenesis, hap- loid round spermatids undergo dramatic biochemical and morphological changes that are governed by specialized gene expression and interactions between various genes and their protein products [6]. Identification of genes involved in sperm development is a prerequisite to under- standing the molecular mechanisms of spermatogenesis. Sperm development is known to be disrupted during spermiogenesis in several acrosomal defects; e.g. globo- zoospermia in humans, where spermatozoa lack an © 2010 Sironen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.