Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle

International audienceAbstractBackgroundWhite spotting of the coat is a characteristic trait of various domestic species including cattle and other mammals. It is a hallmark of Holstein–Friesian cattle, and several previous studies have detected genetic loci with major effects for white spotting in animals with Holstein–Friesian ancestry. Here, our aim was to better understand the underlying genetic and molecular mechanisms of white spotting, by conducting the largest mapping study for this trait in cattle, to date.ResultsUsing imputed whole-genome sequence data, we conducted a genome-wide association analysis in 2973 mixed-breed cows and bulls. Highly significant quantitative trait loci (QTL) were found on chromosomes 6 and 22, highlighting the well-established coat color genes KIT and MITF as likely responsible for these effects. These results are in broad agreement with previous studies, although we also report a third significant QTL on chromosome 2 that appears to be novel. This signal maps immediately adjacent to the PAX3 gene, which encodes a known transcription factor that controls MITF expression and is the causal locus for white spotting in horses. More detailed examination of these loci revealed a candidate causal mutation in PAX3 (p.Thr424Met), and another candidate mutation (rs209784468) within a conserved element in intron 2 of MITF transcripts expressed in the skin. These analyses also revealed a mechanistic ambiguity at the chromosome 6 locus, where highly dispersed association signals suggested multiple or multiallelic QTL involving KIT and/or other genes in this region.ConclusionsOur findings extend those of previous studies that reported KIT as a likely causal gene for white spotting, and report novel associations between candidate causal mutations in both the MITF and PAX3 genes. The sizes of the effects of these QTL are substantial, and could be used to select animals with darker, or conversely whiter, coats depending on the desired characteristics

Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle

International audienceAbstractBackgroundWhite spotting of the coat is a characteristic trait of various domestic species including cattle and other mammals. It is a hallmark of Holstein–Friesian cattle, and several previous studies have detected genetic loci with major effects for white spotting in animals with Holstein–Friesian ancestry. Here, our aim was to better understand the underlying genetic and molecular mechanisms of white spotting, by conducting the largest mapping study for this trait in cattle, to date.ResultsUsing imputed whole-genome sequence data, we conducted a genome-wide association analysis in 2973 mixed-breed cows and bulls. Highly significant quantitative trait loci (QTL) were found on chromosomes 6 and 22, highlighting the well-established coat color genes KIT and MITF as likely responsible for these effects. These results are in broad agreement with previous studies, although we also report a third significant QTL on chromosome 2 that appears to be novel. This signal maps immediately adjacent to the PAX3 gene, which encodes a known transcription factor that controls MITF expression and is the causal locus for white spotting in horses. More detailed examination of these loci revealed a candidate causal mutation in PAX3 (p.Thr424Met), and another candidate mutation (rs209784468) within a conserved element in intron 2 of MITF transcripts expressed in the skin. These analyses also revealed a mechanistic ambiguity at the chromosome 6 locus, where highly dispersed association signals suggested multiple or multiallelic QTL involving KIT and/or other genes in this region.ConclusionsOur findings extend those of previous studies that reported KIT as a likely causal gene for white spotting, and report novel associations between candidate causal mutations in both the MITF and PAX3 genes. The sizes of the effects of these QTL are substantial, and could be used to select animals with darker, or conversely whiter, coats depending on the desired characteristics

A comparison of reproductive performance and physiology of three genotypes of Holstein Friesian dairy cattle : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University, Palmerston North, New Zealand

It is important to achieve a consistently high reproductive performance in the seasonal, pastoral-based dairy production systems found in New Zealand. A decline in dairy cattle reproductive performance has been reported in many countries and this decline has been suggested to be due to the incorporation of Holstein genetics into the Friesian populations. The use of Holstein genetics (referred to as overseas genetics) has increased rapidly in New Zealand in the past 10 years. This thesis investigates the reproductive performance and physiology of animals in the Dexcel Holstein Friesian Strain Trial, from the onset of puberty, through to the end of the second lactation in a pasture-based dairy production system (total 272 animals). Two strains of New Zealand genetic origin, of either high (NZH) or low (NZL) genetic merit were compared to high genetic merit Holstein-Friesian animals of overseas genetic origin (predominantly North American and Dutch origin, OS). Differences in live weight at puberty were identified between NZ and overseas strains. Nulliparous OS heifers were found to have longer oestrous cycles and luteal phases than NZ heifers, but pregnancy rates between the strains were not different. Body condition score at calving was found to be an important predictor of the length of the postpartum anovulatory interval. Postpartum anovulatory intervals were significantly shorter (p<0.05) in OS than NZH animals. Final pregnancy rates were not different between the strains. The timing of luteal regression, following an unsuccessful first insemination was found to be more variable in OS than NZH cows, with some OS cows initiating luteal regression prior to the timing of maternal recognition of pregnancy. The results from this thesis showed that there are differences in reproductive performance between the strains and that some OS animals are able to perform well in pasture-based dairy production systems. In conclusion, provided OS genetics are proven in New Zealand before they are widely used, there is no reason to recommend against the use of OS Holstein Friesian genetics. Further investigations should focus on the area of body condition score mobilisation and the control of the timing of luteolysis, which are areas where differences between the strains were identified