Association of Copy Number Variation at Intron 3 of HMGA2 With Navel Length in Bos indicus.

Navel injuries caused by friction against the pasture can promote infection, reproductive problems and costly treatments in beef cattle raised in extensive systems. A haplotype-based genome-wide association study (GWAS) was performed for visual scores of navel length at yearling in Nellore cattle (Bos indicus) using data from 2,016 animals and 503,088 single nucleotide polymorphism (SNP) markers. The strongest signal (p = 1.01 × 10-9) was found on chromosome 5 spanning positions 47.9-48.2 Mbp. This region contains introns 3 and 4 and exons 4 and 5 of the high mobility group AT-hook 2 gene (HMGA2). Further inspection of the region with whole genome sequence data of 21 Nellore bulls revealed correlations between counts of the significant haplotype and copy number gains of a ∼6.2 kbp segment of intron 3 of HMGA2. Analysis of genome sequences from five African B. indicus and four European Bos taurus breeds revealed that the copy number variant (CNV) is indicine-specific. This intronic CNV was then validated through quantitative polymerase chain reaction (qPCR) using Angus animals as copy neutral controls. Importantly, the CNV was not detectable by means of conventional SNP-based GWAS or SNP probe intensity analyses. Given that HMGA2 affects the expression of the insulin-like growth factor 2 gene (IGF2) together with the pleomorphic adenoma gene 1 (PLAG1), and that the latter has been repeatedly shown to be associated with quantitative traits of economic importance in cattle, these findings highlight the emerging role of variants impacting the insulin-like growth factor pathway to cattle breeding.

Combining Landscape Genomics and Ecological Modelling to Investigate Local Adaptation of Indigenous Ugandan Cattle to East Coast Fever.

East Coast fever (ECF) is a fatal sickness affecting cattle populations of eastern, central, and southern Africa. The disease is transmitted by the tick Rhipicephalus appendiculatus, and caused by the protozoan Theileria parva parva, which invades host lymphocytes and promotes their clonal expansion. Importantly, indigenous cattle show tolerance to infection in ECF-endemically stable areas. Here, the putative genetic bases underlying ECF-tolerance were investigated using molecular data and epidemiological information from 823 indigenous cattle from Uganda. Vector distribution and host infection risk were estimated over the study area and subsequently tested as triggers of local adaptation by means of landscape genomics analysis. We identified 41 and seven candidate adaptive loci for tick resistance and infection tolerance, respectively. Among the genes associated with the candidate adaptive loci are PRKG1 and SLA2. PRKG1 was already described as associated with tick resistance in indigenous South African cattle, due to its role into inflammatory response. SLA2 is part of the regulatory pathways involved into lymphocytes' proliferation. Additionally, local ancestry analysis suggested the zebuine origin of the genomic region candidate for tick resistance.

A PLAG1 mutation contributed to stature recovery in modern cattle.

The recent evolution of cattle is marked by fluctuations in body size. Height in the Bos taurus lineage was reduced by a factor of ~1.5 from the Neolithic to the Middle Ages, and increased again only during the Early Modern Ages. Using haplotype analysis, we found evidence that the bovine PLAG1 mutation (Q) with major effects on body size, weight and reproduction is a >1,000 years old derived allele that increased rapidly in frequency in Northwestern European B. taurus between the 16th and 18th centuries. Towards the 19th and 20th centuries, Q was introgressed into non-European B. taurus and Bos indicus breeds. These data implicate a major role of Q in recent changes in body size in modern cattle, and represent one of the first examples of a genomic sweep in livestock that was driven by selection on a complex trait.

Evidence of Bos javanicus x Bos indicus hybridization and major QTLs for birth weight in Indonesian Peranakan Ongole cattle.

BACKGROUND: Peranakan Ongole (PO) is a major Indonesian Bos indicus breed that derives from animals imported from India in the late 19(th) century. Early imports were followed by hybridization with the Bos javanicus subspecies of cattle. Here, we used genomic data to partition the ancestry components of PO cattle and map loci implicated in birth weight. RESULTS: We found that B. javanicus contributes about 6-7% to the average breed composition of PO cattle. Only two nearly fixed B. javanicus haplotypes were identified, suggesting that most of the B. javanicus variants are segregating under drift or by the action of balancing selection. The zebu component of the PO genome was estimated to derive from at least two distinct ancestral pools. Additionally, well-known loci underlying body size in other beef cattle breeds, such as the PLAG1 region on chromosome 14, were found to also affect birth weight in PO cattle. CONCLUSIONS: This study is the first attempt to characterize PO at the genome level, and contributes evidence of successful, stabilized B. indicus x B. javanicus hybridization. Additionally, previously described loci implicated in body size in worldwide beef cattle breeds also affect birth weight in PO cattle.

Detecting loci under recent positive selection in dairy and beef cattle by combining different genome-wide scan methods.

As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP) data generated from dairy and beef cattle (taurine and indicine). The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P<3.17×10(-7)) population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3) in Brown Swiss (P = 3.82×10(-12)), and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection.