Rapid selection of milk mid-infrared spectra for creating a dairy cow population world representative spectral database.

The advantage of employing mid-infrared spectrometry for milk analysis in breeding lies in its ability to quickly generate millions of records. However, these records may be biased if the calibration process does not account for their spectral variability when constructing the predictive model. Therefore, this study introduces a novel method for developing a world representative spectral database (WRSD) to reduce the risks of spectral extrapolation when predicting dairy traits in new samples.

A common regulatory haplotype doubles lactoferrin concentration in milk.

Background: Bovine lactoferrin (Lf) is an iron absorbing whey protein with antibacterial, antiviral, and antifungal activity. Lactoferrin is economically valuable and has an extremely variable concentration in milk, partly driven by environmental influences such as milking frequency, involution, or mastitis. A significant genetic influence has also been previously observed to regulate lactoferrin content in milk.

Identification of candidate novel production variants on the Bos taurus chromosome X.

Chromosome X is often excluded from bovine genetic studies due to complications caused by the sex specific nature of the chromosome. As chromosome X is the second largest cattle chromosome and makes up approximately 6% of the female genome, finding ways to include chromosome X in dairy genetic studies is important. Using female animals and treating chromosome X as an autosome, we performed X chromosome inclusive genome-wide association studies in the selective breeding environment of the New Zealand dairy industry, aiming to identify chromosome X variants associated with milk production traits.

Comparison of the genetic characteristics of directly measured and Fourier-transform mid-infrared-predicted bovine milk fatty acids and proteins.

Fourier-transform mid-infrared (FT-MIR) spectroscopy is a high-throughput and inexpensive methodology used to evaluate concentrations of fat and protein in dairy cattle milk samples. The objective of this study was to compare the genetic characteristics of FT-MIR predicted fatty acids and individual milk proteins with those that had been measured directly using gas and liquid chromatography methods. The data used in this study was based on 2,005 milk samples collected from 706 Holstein-Friesian × Jersey animals that were managed in a seasonal, pasture-based dairy system, with milk samples collected across 2 consecutive seasons.

Screening for phenotypic outliers identifies an unusually low concentration of a β-lactoglobulin B protein isoform in bovine milk caused by a synonymous SNP.

Background: Milk samples from 10,641 dairy cattle were screened by a mass spectrometry method for extreme concentrations of the A or B isoforms of the whey protein, β-lactoglobulin (BLG), to identify causative genetic variation driving changes in BLG concentration.

Results: A cohort of cows, from a single sire family, was identified that produced milk containing a low concentration of the BLG B protein isoform. A genome-wide association study (GWAS) of BLG B protein isoform concentration in milk from AB heterozygous cows, detected a group of highly significant single nucleotide polymorphisms (SNPs) within or close to the BLG gene.

Pregnancy status predicted using milk mid-infrared spectra from dairy cattle.

Accurate and timely pregnancy diagnosis is an important component of effective herd management in dairy cattle. Predicting pregnancy from Fourier-transform mid-infrared (FT-MIR) spectroscopy data is of particular interest because the data are often already available from routine milk testing. The purpose of this study was to evaluate how well pregnancy status could be predicted in a large data set of 1,161,436 FT-MIR milk spectra records from 863,982 mixed-breed pasture-based New Zealand dairy cattle managed within seasonal calving systems.

Non-additive QTL mapping of lactation traits in 124,000 cattle reveals novel recessive loci.

Background: Deleterious recessive conditions have been primarily studied in the context of Mendelian diseases. Recently, several deleterious recessive mutations with large effects were discovered via non-additive genome-wide association studies (GWAS) of quantitative growth and developmental traits in cattle, which showed that quantitative traits can be used as proxies of genetic disorders when such traits are indicative of whole-animal health status. We reasoned that lactation traits in cattle might also reflect genetic disorders, given the increased energy demands of lactation and the substantial stresses imposed on the animal.

Sequence-based genome-wide association study of individual milk mid-infrared wavenumbers in mixed-breed dairy cattle.

Background: Fourier-transform mid-infrared (FT-MIR) spectroscopy provides a high-throughput and inexpensive method for predicting milk composition and other novel traits from milk samples. While there have been many genome-wide association studies (GWAS) conducted on FT-MIR predicted traits, there have been few GWAS for individual FT-MIR wavenumbers. Using imputed whole-genome sequence for 38,085 mixed-breed New Zealand dairy cattle, we conducted GWAS on 895 individual FT-MIR wavenumber phenotypes, and assessed the value of these direct phenotypes for identifying candidate causal genes and variants, and improving our understanding of the physico-chemical properties of milk.

Non-additive association analysis using proxy phenotypes identifies novel cattle syndromes.

Mammalian species carry ~100 loss-of-function variants per individual, where ~1-5 of these impact essential genes and cause embryonic lethality or severe disease when homozygous. The functions of the remainder are more difficult to resolve, although the assumption is that these variants impact fitness in less manifest ways. Here we report one of the largest sequence-resolution screens of cattle to date, targeting discovery and validation of non-additive effects in 130,725 animals.

A new mechanism for a familiar mutation - bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement.

Background: The DGAT1 gene encodes an enzyme responsible for catalysing the terminal reaction in mammary triglyceride synthesis, and underpins a well-known pleiotropic quantitative trait locus (QTL) with a large influence on milk composition phenotypes. Since first described over 15 years ago, a protein-coding variant K232A has been assumed as the causative variant underlying these effects, following in-vitro studies that demonstrated differing levels of triglyceride synthesis between the two protein isoforms.

Results: We used a large RNAseq dataset to re-examine the underlying mechanisms of this large milk production QTL, and hereby report novel expression-based functions of the chr14 g.

The evolving role of Fourier-transform mid-infrared spectroscopy in genetic improvement of dairy cattle.

Over the last 100 years, significant advances have been made in the characterisation of milk composition for dairy cattle improvement programs. Technological progress has enabled a shift from labour intensive, on-farm collection and processing of samples that assess yield and fat levels in milk, to large-scale processing of samples through centralised laboratories, with the scope extended to include quantification of other traits. Fourier-transform mid-infrared (FT-MIR) spectroscopy has had a significant role in the transformation of milk composition phenotyping, with spectral-based predictions of major milk components already being widely used in milk payment and animal evaluation systems globally.

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

Background: White 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.

Strategies for noise reduction and standardization of milk mid-infrared spectra from dairy cattle.

The use of Fourier-transform mid-infrared (FTIR) spectroscopy is of interest to the dairy industry worldwide for predicting milk composition and other novel traits that are difficult or expensive to measure directly. Although there are many valuable applications for FTIR spectra, noise from differences in spectral responses between instruments is problematic because it reduces prediction accuracy if ignored. The purpose of this study was to develop strategies to reduce the impact of noise and to compare methods for standardizing FTIR spectra in order to reduce between-instrument variability in multiple-instrument networks.

Multiple QTL underlie milk phenotypes at the CSF2RB locus.

Background: Over many years, artificial selection has substantially improved milk production by cows. However, the genes that underlie milk production quantitative trait loci (QTL) remain relatively poorly characterised. Here, we investigate a previously reported QTL located at the CSF2RB locus on chromosome 5, for several milk production phenotypes, to better understand its underlying genetic and molecular causes.

Widespread -regulation of RNA editing in a large mammal.

Post-transcriptional RNA editing may regulate transcript expression and diversity in cells, with potential impacts on various aspects of physiology and environmental adaptation. A small number of recent genome-wide studies in , mouse, and human have shown that RNA editing can be genetically modulated, highlighting loci that quantitatively impact editing of transcripts. The potential gene expression and physiological consequences of these RNA-editing quantitative trait loci (edQTL), however, are almost entirely unknown.

Identification of an immune modulation locus utilising a bovine mammary gland infection challenge model.

Inflammation of the mammary gland following bacterial infection, commonly known as mastitis, affects all mammalian species. Although the aetiology and epidemiology of mastitis in the dairy cow are well described, the genetic factors mediating resistance to mammary gland infection are not well known, due in part to the difficulty in obtaining robust phenotypic information from sufficiently large numbers of individuals. To address this problem, an experimental mammary gland infection experiment was undertaken, using a Friesian-Jersey cross breed F2 herd.

Mating strategies to maximize genetic merit in dairy cattle herds.

The genetic merit of a herd is a key determinant in productivity for dairy farmers. However, making breeding decisions to maximize the rate of genetic gain can be complex because there is no certainty about which cows will become pregnant with a heifer calf. In this study, breeding worth (BrW) was used as a measure of genetic merit, and several mating strategies were evaluated.

DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content.

Background: Lactose provides an easily-digested energy source for neonates, and is the primary carbohydrate in milk in most species. Bovine lactose is also a key component of many human food products. However, compared to analyses of other milk components, the genetic control of lactose has been little studied.

Bovine mammary gland X chromosome inactivation.

X chromosome inactivation (XCI) is a process by which 1 of the 2 copies of the X chromosomes present in female mammals is inactivated. The transcriptional silencing of one X chromosome achieves dosage compensation between XX females and XY males and ensures equal expression of X-linked genes in both sexes. Although all mammals use this form of dosage compensation, the complex mechanisms that regulate XCI vary between species, tissues, and development.

Detection and assessment of copy number variation using PacBio long-read and Illumina sequencing in New Zealand dairy cattle.

Single nucleotide polymorphisms have been the DNA variant of choice for genomic prediction, largely because of the ease of single nucleotide polymorphism genotype collection. In contrast, structural variants (SV), which include copy number variants (CNV), translocations, insertions, and inversions, have eluded easy detection and characterization, particularly in nonhuman species. However, evidence increasingly shows that SV not only contribute a substantial proportion of genetic variation but also have significant influence on phenotypes.

Sequence-based Association Analysis Reveals an MGST1 eQTL with Pleiotropic Effects on Bovine Milk Composition.

The mammary gland is a prolific lipogenic organ, synthesising copious amounts of triglycerides for secretion into milk. The fat content of milk varies widely both between and within species, and recent independent genome-wide association studies have highlighted a milk fat percentage quantitative trait locus (QTL) of large effect on bovine chromosome 5. Although both EPS8 and MGST1 have been proposed to underlie these signals, the causative status of these genes has not been functionally confirmed.

Lactation traits associated with short- and long-term once-daily milking performance in New Zealand crossbred dairy cattle.

The main objectives of this study were to establish the relative value of milk yields under twice-daily milking (TDM) as a predictor of yield and yield loss under once-daily milking (ODM), and to understand the role of residual milk and udder storage capacity-related traits in regulating yield and yield loss during ODM. A Holstein-Friesian × Jersey crossbred herd was established over 2 seasons (years), as 2 individual cohorts on the same farm, managed on a pasture-based system over 4 lactations. Short-term (1-wk) ODM studies, with a starting total of 690 cows, were undertaken in mid- and late-lactation in lactation 2 and in mid-lactation in lactation 3 for each cohort.

Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.

Milk is composed of a complex mixture of lipids, proteins, carbohydrates and various vitamins and minerals as a source of nutrition for young mammals. The composition of milk varies between individuals, with lipid composition in particular being highly heritable. Recent reports have highlighted a region of bovine chromosome 27 harbouring variants affecting milk fat percentage and fatty acid content.