We investigated diverse genomic selections using high-density single nucleotide polymorphism data of five distinct cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-known genes such as KIT, MC1R, ASIP, GHR, LCORL, NCAPG, WIF1, and ABCA12, we found evidence for a variety of novel and less-known genes under selection in cattle, such as LAP3, SAR1B, LRIG3, FGF5, and NUDCD3. Selective sweeps near LAP3 were then validated by next-generation sequencing. Genome-wide association analysis involving 26,362 Holsteins confirmed that LAP3 and SAR1B were related to milk production traits, suggesting that our candidate regions were likely functional. In addition, haplotype network analyses further revealed distinct selective pressures and evolution patterns across these five cattle breeds. Our results provided a glimpse into diverse genomic selection during cattle domestication, breed formation, and recent genetic improvement. These findings will facilitate genome-assisted breeding to improve animal production and health.

BackgroundGrowth and meat production traits are significant economic traits in sheep. The aim of the study is to identify candidate genes affecting growth and meat production traits at genome level with high throughput single nucleotide polymorphisms (SNP) genotyping technologies.Methodology and ResultsUsing Illumina OvineSNP50 BeadChip, we performed a GWA study in 329 purebred sheep for 11 growth and meat production traits (birth weight, weaning weight, 6-month weight, eye muscle area, fat thickness, pre-weaning gain, post-weaning gain, daily weight gain, height at withers, chest girth, and shin circumference). After quality control, 319 sheep and 48,198 SNPs were analyzed by TASSEL program in a mixed linear model (MLM). 36 significant SNPs were identified for 7 traits, and 10 of them reached genome-wise significance level for post-weaning gain. Gene annotation was implemented with the latest sheep genome Ovis_aries_v3.1 (released October 2012). More than one-third SNPs (14 out of 36) were located within ovine genes, others were located close to ovine genes (878bp-398,165bp apart). The strongest new finding is 5 genes were thought to be the most crucial candidate genes associated with post-weaning gain: s58995.1 was located within the ovine genes MEF2B and RFXANK, OAR3_84073899.1, OAR3_115712045.1 and OAR9_91721507.1 were located within CAMKMT, TRHDE, and RIPK2 respectively. GRM1, POL, MBD5, UBR2, RPL7 and SMC2 were thought to be the important candidate genes affecting post-weaning gain too. Additionally, 25 genes at chromosome-wise significance level were also forecasted to be the promising genes that influencing sheep growth and meat production traits.ConclusionsThe results will contribute to the similar studies and facilitate the potential utilization of genes involved in growth and meat production traits in sheep in future.

BackgroundMilk production is an economically important sector of global agriculture. Much attention has been paid to the identification of quantitative trait loci (QTL) associated with milk, fat, and protein yield and the genetic and molecular mechanisms underlying them. Copy number variation (CNV) is an emerging class of variants which may be associated with complex traits.ResultsIn this study, we performed a genome-wide association between CNVs and milk production traits in 26,362 Holstein bulls and cows. A total of 99 candidate CNVs were identified using Illumina BovineSNP50 array data, and association tests for each production trait were performed using a linear regression analysis with PCA correlation. A total of 34 CNVs on 22 chromosomes were significantly associated with at least one milk production trait after false discovery rate (FDR) correction. Some of those CNVs were located within or near known QTL for milk production traits. We further investigated the relationship between associated CNVs with neighboring SNPs. For all 82 combinations of traits and CNVs (less than 400 kb in length), we found 17 cases where CNVs directly overlapped with tag SNPs and 40 cases where CNVs were adjacent to tag SNPs. In 5 cases, CNVs located were in strong linkage disequilibrium with tag SNPs, either within or adjacent to the same haplotype block. There were an additional 20 cases where CNVs did not have a significant association with SNPs, suggesting that the effects of those CNVs were probably not captured by tag SNPs.ConclusionWe conclude that combining CNV with SNP analyses reveals more genetic variations underlying milk production traits than those revealed by SNPs alone.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-683) contains supplementary material, which is available to authorized users.

BackgroundIn recent years, genome-wide association studies have successfully uncovered single-nucleotide polymorphisms (SNPs) associated with complex traits such as diseases and quantitative phenotypes. These variations account for a small proportion of heritability. With the development of high throughput techniques, abundant submicroscopic structural variations have been found in organisms, of which the main variations are copy number variations (CNVs). Therefore, CNVs are increasingly recognized as an important and abundant source of genetic variation and phenotypic diversity.ResultsAnalyses of CNVs in the genomes of three sheep breeds were performed using the Ovine SNP50 BeadChip array. A total of 238 CNV regions (CNVRs) were identified, including 219 losses, 13 gains, and six with both events (losses and gains), which cover 60.35 Mb of the sheep genomic sequence and correspond to 2.27% of the autosomal genome sequence. The length of the CNVRs on autosomes range from 13.66 kb to 1.30 Mb with a mean size of 253.57 kb, and 75 CNVRs events had a frequency > 3%. Among these CNVRs, 47 CNVRs identified by the PennCNV overlapped with the CNVpartition. Functional analysis indicated that most genes in the CNVRs were significantly enriched for involvement in the environmental response. Furthermore, 10 CNVRs were selected for validation and 6 CNVRs were further experimentally confirmed by qPCR. In addition, there were 57 CNVRs overlapped in our new dataset and other published ruminant CNV studies.ConclusionsIn this study, we firstly constructed a sheep CNV map based on the Ovine SNP50 array. Our results demonstrated the differences of two detection tools and integration of multiple algorithms can enhance the detection of sheep genomic structure variations. Furthermore, our findings would be of help for understanding the sheep genome and provide preliminary foundation for carrying out the CNVs association studies with economically important phenotypes of sheep in the future.

The diversity and population genetics of copy number variation (CNV) in domesticated animals are not well understood. In this study, we analysed 75 genomes of major taurine and indicine cattle breeds (including Angus, Brahman, Gir, Holstein, Jersey, Limousin, Nelore, and Romagnola), sequenced to 11-fold coverage to identify 1,853 non-redundant CNV regions. Supported by high validation rates in array comparative genomic hybridization (CGH) and qPCR experiments, these CNV regions accounted for 3.1% (87.5 Mb) of the cattle reference genome, representing a significant increase over previous estimates of the area of the genome that is copy number variable (∼2%). Further population genetics and evolutionary genomics analyses based on these CNVs revealed the population structures of the cattle taurine and indicine breeds and uncovered potential diversely selected CNVs near important functional genes, including AOX1, ASZ1, GAT, GLYAT, and KRTAP9-1. Additionally, 121 CNV gene regions were found to be either breed specific or differentially variable across breeds, such as RICTOR in dairy breeds and PNPLA3 in beef breeds. In contrast, clusters of the PRP and PAG genes were found to be duplicated in all sequenced animals, suggesting that subfunctionalization, neofunctionalization, or overdominance play roles in diversifying those fertility-related genes. These CNV results provide a new glimpse into the diverse selection histories of cattle breeds and a basis for correlating structural variation with complex traits in the future.

BackgroundApart from single nucleotide polymorphism (SNP), copy number variation (CNV) is another important type of genetic variation, which may affect growth traits and play key roles for the production of beef cattle. To date, no genome-wide association study (GWAS) for CNV and body traits in beef cattle has been reported, so the present study aimed to investigate this type of association in one of the most important cattle subspecies: Bos indicus (Nellore breed).ResultsWe have used intensity data from over 700,000 SNP probes across the bovine genome to detect common CNVs in a sample of 2230 Nellore cattle, and performed GWAS between the detected CNVs and nine growth traits. After filtering for frequency and length, a total of 231 CNVs ranging from 894 bp to 4,855,088 bp were kept and tested as predictors for each growth trait using linear regression analysis with principal components correction. There were 49 significant associations identified among 17 CNVs and seven body traits after false discovery rate correction (P < 0.05). Among the 17 CNVs, three were significant or marginally significant for all the traits. We have compared the locations of associated CNVs with quantitative trait locus and the RefGene database, and found two sets of 9 CNVs overlapping with either known QTLs or genes, respectively. The gene overlapping with CNV100, KCNJ12, is a functional candidate for muscle development and plays critical roles in muscling traits.ConclusionThis study presents the first CNV-based GWAS of growth traits using high density SNP microarray data in cattle. We detected 17 CNVs significantly associated with seven growth traits and one of them (CNV100) may be involved in growth traits through KCNJ12.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2461-4) contains supplementary material, which is available to authorized users.

While single nucleotide polymorphism (SNP) is typically the variant of choice for population genetics, copy number variation (CNV) which comprises insertion, deletion and duplication of genomic sequence, is an informative type of genetic variation. CNVs have been shown to be both common in mammals and important for understanding the relationship between genotype and phenotype. However, CNV differentiation, selection and its population genetic properties are not well understood across diverse populations. We performed a population genetics survey based on CNVs derived from the BovineHD SNP array data of eight distinct cattle breeds. We generated high resolution results that show geographical patterns of variations and genome-wide admixture proportions within and among breeds. Similar to the previous SNP-based studies, our CNV-based results displayed a strong correlation of population structure and geographical location. By conducting three pairwise comparisons among European taurine, African taurine, and indicine groups, we further identified 78 unique CNV regions that were highly differentiated, some of which might be due to selection. These CNV regions overlapped with genes involved in traits related to parasite resistance, immunity response, body size, fertility, and milk production. Our results characterize CNV diversity among cattle populations and provide a list of lineage-differentiated CNVs.

The recent discovery of bovine haplotypes with negative effects on fertility in the Brown Swiss, Holstein, and Jersey breeds has allowed producers to identify carrier animals using commercial single nucleotide polymorphism (SNP) genotyping assays. This study was devised to identify the causative mutations underlying defective bovine embryo development contained within three of these haplotypes (Brown Swiss haplotype 1 and Holstein haplotypes 2 and 3) by combining exome capture with next generation sequencing. Of the 68,476,640 sequence variations (SV) identified, only 1,311 genome-wide SNP were concordant with the haplotype status of 21 sequenced carriers. Validation genotyping of 36 candidate SNP identified only 1 variant that was concordant to Holstein haplotype 3 (HH3), while no variants located within the refined intervals for HH2 or BH1 were concordant. The variant strictly associated with HH3 is a non-synonymous SNP (T/C) within exon 24 of the Structural Maintenance of Chromosomes 2 (SMC2) on Chromosome 8 at position 95,410,507 (UMD3.1). This polymorphism changes amino acid 1135 from phenylalanine to serine and causes a non-neutral, non-tolerated, and evolutionarily unlikely substitution within the NTPase domain of the encoded protein. Because only exome capture sequencing was used, we could not rule out the possibility that the true causative mutation for HH3 might lie in a non-exonic genomic location. Given the essential role of SMC2 in DNA repair, chromosome condensation and segregation during cell division, our findings strongly support the non-synonymous SNP (T/C) in SMC2 as the likely causative mutation. The absence of concordant variations for HH2 or BH1 suggests either the underlying causative mutations lie within a non-exomic region or in exome regions not covered by the capture array.