Fontanesi et al. BMC Genomics 2010, 11:639 http://www.biomedcentral.com/1471-2164/11/639 the goat from the cattle and sheep [4-6] made it possible to use microsatellites developed in these two species to successfully genotype goats, even though interspecific priming often resulted in a marked loss of heterozygos- ity [2,3]. A comparative cytogenetic map of the goat genome has been developed using cattle and sheep BAC clones [3]. This map has been improved adding many other physically mapped genes, as recently reviewed in a compiled list including 268 genes and 144 microsatel- lites, roughly including 65% of the goat chromosome bands [7]. Comparative mapping between cattle and goat (both species have 2n = 60) has shown only few rearrangements in agreement with the similarity of chromosome banding [7,8]. Analysis of the goat genome provided a few important findings including the positional cloning of the polled intersex syndrome (PIS) locus located on goat chromo- some (CHI) 1q43 and determined by a deletion of 11.7 kb containing mainly repetitive sequences [9,10]. Addi- tional studies have been focused on milk protein gene polymorphisms and their effects on milk production traits (e.g. [11-13]). Polymorphisms in the goat PRNP gene have been associated with susceptibility to scrapie in different breeds [14]. Few other studies reported QTL for milk and fleece production traits and disease resis- tance [15-20]. Investigations of genes affecting coat col- our identified polymorphisms associated with this phenotypic trait [21,22]. In particular, the Agouti locus in goat was shown to be highly variable including mis- sense mutations and copy number variation (CNV) [22]. Recent studies have shown that copy number variants, defined as intraspecific gains or losses of ≥ 1 kb of geno- mic DNA [23,24], represent an important source of varia- bility of mammalian genomes (~0.4-25% of the genome) as reported in human (e.g. [25-34]), chimpanzee [35,36], rhesus macaque [37], mouse [38-42], rat [43,44], dog [45,46], pig [47], and cattle [48-52]. CNVs can change gene structure and dosage, can regulate gene expression and function and for these reasons they have potentially more effects than the most frequent single nucleotide polymorphisms (SNPs) in determining phenotypic differ- ences [43,53-56]. CNVs can represent benign poly- morphic variants even if in many other cases they are associated with human Mendelian and complex genetic disorders (reviewed in [57,58]). In farm animals, several traits are caused by CNV affecting genes or gene regions. For example, the Dominant white locus in pigs includes alleles determined by duplications of the KIT gene [59,60]. CNV also affects the Agouti locus in sheep and goats and contributes to the variability of coat colour in these two species [22,61]. CNV in intron 1 of the SOX5 gene causes the pea-comb phenotype in chicken [62] and the late feathering locus in this avian species includes a partial duplication of the PRLR and SPEF2 genes [63]. Page 2 of 15 Genome-wide discovery and frequency evaluation of CNVs have been possible with the development of high-resolution array comparative genome hybridisa- tion (aCGH) and, subsequently, with data analysis of high-density SNP platforms and paired end and deep sequencing approaches [64-69]. An advantage of aCGH is that hybridisation can be performed using heterolo- gous DNA, i.e. genomic DNA of a different species but close to that used to develop the array, taking advan- tages from completely sequenced, assembled, and richly annotated genomes. Cross species aCGH experi- ments have been successfully applied using human arrays to analyse CNVs in chimpanzee and other pri- mates [35,36,70], and using chicken based arrays to identify CNVs in turkey [71], duck [72], and zebra- finch [73] genomes. Here we designed a cross species cattle-goat aCGH experiment in order to identify CNVs in goats of differ- ent breeds (both cosmopolitan and local) using informa- tion of the cattle genome and we obtained a first comparative map of CNVs of the Capra hircus genome. Results and discussion Identification of goat CNVs and comparative analysis between goat and cattle CNVRs The goat genome has not been sequenced yet and the cattle is the closest species to the goat for which an assembled genome is available [74,75]. In order to give a preliminary evaluation of the extent of sequence identity between these two ruminant species, we compared goat genomic sequences longer than 1 kb available in EMBL database with homologous cattle genomic regions. The average sequence identity between these two species was 82.79% (over 166.8 kb of aligned sequences), that increased at 93.77% if only exonic sequences (32.5 kb) were considered (data not shown). Even if this rough evaluation cannot give a complete picture of sequence divergence between cattle and goat, it indicates that cat- tle-goat cross-species DNA hybridization is possible as also demonstrated in physical mapping of cattle BAC and YAC clones to the goat genome and vice versa as well as by interspecific use of microsatellites [2,3,7,76]. Therefore, to identify CNVs in goats, we carried out a cross-species aCGH experiment using a cattle (Bos taurus) custom tiling array including ~385,000 oligonu- cleotide probes and goat genomic DNA obtained from 9 goats of four different breeds (3 Saanen, 1 Camosciata delle Alpi, 3 Girgentana, and 2 Murciano-Granadina goats), chosen according to their differences in produc- tion and morphological traits, and origin (Figure 1). Saa- nen is the most popular dairy breed that was originated in Switzerland, highly selected for heavy milk production and with completely white/cream coat colour. Camos- ciata delle Alpi is an Alp mountain breed of the