Abstract
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.
Highlights
Navel length at yearling (NY) is an economically important trait in beef cattle raised in extensive production systems
A naturally occurring pleomorphic adenoma gene 1 (PLAG1) mutation has been shown to affect a wide range of economically relevant traits in both B. taurus (Karim et al, 2011; Bolormaa et al, 2014; Saatchi et al, 2014) and B. indicus (Fortes et al, 2013; Utsunomiya et al, 2013; Pereira et al, 2016) cattle, implicating a major contribution of variants impacting the insulin-like growth factor (IGF) system to genetic variance of several traits in the bovine species
The discovery of multiple quantitative trait loci (QTL) mapping to the bovine PLAG1 chromosomal domain opens the question of whether other regulatory genes and variants affecting the expression of IGF1 and insulin-like growth factor gene 2 (IGF2) might lead to phenotypic differences of economical relevance in cattle
Summary
Navel length at yearling (NY) is an economically important trait in beef cattle raised in extensive production systems. A pendulous navel increases the risk of injuries caused by friction against the pasture, leading to infection, reproductive impairment and treatment expenses (Ashdown, 2006; Rabelo et al, 2008; Boligon et al, 2016) This trait is especially important to cattle raised in Brazil, the second largest beef exporter of the world, where Nellore (Bos indicus) animals compose the majority of the herds and approximately 88% of the females in reproductive age are subjected to natural mating (Asbia, 2016). A recent genome-wide association study (GWAS) for body weight and carcass visual scores in Nellore cattle revealed pleiotropic loci sheltering genes that are known to modulate the insulin-like growth factor (IGF) or somatomedin pathway (Pereira et al, 2016). Genome-wide scans for visual scores of navel length were not yet reported in B. indicus cattle, leaving opened the question of whether polymorphisms in PLAG1 or any other modulator of the IGF pathway contribute to the genetic variance of navel length in that species
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