BackgroundRecently, the discovery of copy number variation (CNV) led researchers to think that there are more variations of genomic DNA than initially believed. Moreover, a certain CNV region has been found to be associated with the onset of diseases. Therefore, CNV is now known as an important genomic variation in biological mechanisms. However, most CNV studies have only involved the human genome. The study of CNV involving other animals, including cattle, is severely lacking.ResultsIn our study of cattle, we used Illumina BovineSNP50 BeadChip (54,001 markers) to obtain each marker's signal intensity (Log R ratio) and allelic intensity (B allele frequency), which led to our discovery of 855 bovine CNVs from 265 cows. For these animals, the average number of CNVs was 3.2, average size was 149.8 kb, and median size was 171.5 kb. Taking into consideration some overlapping regions among the identified bovine CNVs, 368 unique CNV regions were detected. Among them, there were 76 common CNVRs with > 1% CNV frequency. Together, these CNVRs contained 538 genes. Heritability errors of 156 bovine pedigrees and comparative pairwise analyses were analyzed to detect 448 common deletion polymorphisms. Identified variations in this study were successfully validated using visual examination of the genoplot image, Mendelian inconsistency, another CNV identification program, and quantitative PCR.ConclusionsIn this study, we describe a map of bovine CNVs and provide important resources for future bovine genome research. This result will contribute to animal breeding and protection from diseases with the aid of genomic information.

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This study explored the combined effect of number and pattern of mutations in the X ⁄ precore regions of the hepatitis B virus (HBV) genome, mutational complex genotype (MCG), on hepatocellular carcinoma (HCC) development. Sequence variations were determined by direct sequencing and multiplex restriction fragment mass polymorphism analysis in 150 age-, sex-and hepatitis B e antigen (HBeAg) status-matched patients with and without HCC. In addition, a longitudinal study and an external validation of MCG were conducted. All were HBV subgenotype C2. Eight highfrequency mutations (G1613A, C1653T, T1753V, A1762T, G1764A, A1846T, G1896A and G1899A) were significantly associated with HCC. Whereas C1653T, T1753V, G1764A and A1846T were independent mutational factors for HCC, the significance of these individual mutations was negligible when analyzed with all clinico-virological variables. The total number of mutations was the only independent viral factor for HCC, irrespective of HBeAg status. There was a significant dose-risk relationship between the number of mutations and HCC, in which high risks for HCC were associated with mutation numbers ‡6. Pattern analysis of the mutations revealed disparity in distribution among the top seven high-risk mutation combination patterns, which accounted for 40 and 2.7% of HCC and non-HCC cases, respectively. The predictive accuracy of the high-risk mutations for HCC was similar to that of a-fetoprotein. Longitudinal and external validation studies also supported the association of mutation number with HCC development. MCG in the HBV X ⁄ precore regions is a risk indicator for HCC, and might serve as a new guide to the HCC screening scheme for chronic HBV carriers. (Cancer Sci 2012; 103: 296-304) H epatocellular carcinoma (HCC) is a major malignancy worldwide, ranking as the fifth most common cancer. Hepatitis B virus (HBV) infection is a major global cause of HCC, with chronic HBV carriers having a 100-fold increased risk for developing HCC compared to non-carriers.(1) Identification of HCC indicators and risk stratification of patients with chronic HBV infection are essential for guiding appropriate surveillance.Hepatocarcinogenesis as a process in individuals with chronic HBV infection is complex, and involves both host and viral factors. Various viral factors are associated with an increased risk of HCC, including HBV DNA levels, HBeAg status, HBV genotypes, pre-S deletion and mutations in the X ⁄ precore regions.Hepatitis B virus is classified into eight genotypes (A-H), based on an intergroup sequence divergence of 8% or more. HBV genotypes B and C are the predominant types in eastern Asia.(2,3) HBV genotype C is the predominant type in Korea, accounting for more than 95% of Korean chronic HBV carriers.(4,5) Several published studies indicate that carriers infected with HBV genotype C exhibit a high risk of developing HCC, (6,7) but this has not been corroborated. (8,9) In addition to HBV genotype, mutations in the X ⁄ precore regions have been associated with advancement of...

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