Termolecular ion-atom association

Ph.D.MR Flanner

ge-phenos-names

Column names for gene expression phenotypes. These are in a separate file per the GCTA input format requirements

ht-phenos

Herd test phenotypes for 29,350 cows. Used for milk phenotype association analyses

rna-animals-357.vcf

Genotypes for 357 RNAseq cows. Used for eQTL analyses

ht-phenos-names

Column names for herd test phenotypes. These are in a separate file per the GCTA input format requirements

README

The readme file describing this dataset

Multiple QTL underlie milk phenotypes at the CSF2RB locus

Abstract 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. Results Using a population of 29,350 taurine dairy cows, we conducted association analyses for milk yield and composition traits, and identified highly significant QTL for milk yield, milk fat concentration, and milk protein concentration. Strikingly, protein concentration and milk yield appear to show co-located yet genetically distinct QTL. To attempt to understand the molecular mechanisms that might be mediating these effects, gene expression data were used to investigate eQTL for 11 genes in the broader interval. This analysis highlighted genetic impacts on CSF2RB and NCF4 expression that share similar association signatures to those observed for lactation QTL, strongly implicating one or both of these genes as responsible for these effects. Using the same gene expression dataset representing 357 lactating cows, we also identified 38 novel RNA editing sites in the 3′ UTR of CSF2RB transcripts. The extent to which two of these sites were edited also appears to be genetically co-regulated with lactation QTL, highlighting a further layer of regulatory complexity that involves the CSF2RB gene. Conclusions This locus presents a diversity of molecular and lactation QTL, likely representing multiple overlapping effects that, at a minimum, highlight the CSF2RB gene as having a causal role in these processes

HD.milk-animals-29350.grm

GZipped tar file containing the GRM for the 29,350 milk phenotype animals in GCTA binary format. Based on Illumina BovineHD genotypes. Excludes chromosome 5 to enable MLMA-LOCO analyses

Data from: 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. Results: Using a population of 29,350 taurine dairy cows, we conducted association analyses for milk yield and composition traits, and identified highly significant QTL for milk yield, milk fat concentration, and milk protein concentration. Strikingly, protein concentration and milk yield appear to show co-located yet genetically distinct QTL. To attempt to understand the molecular mechanisms that might be mediating these effects, gene expression data were used to investigate eQTL for 11 genes in the broader interval. This analysis highlighted genetic impacts on CSF2RB and NCF4 expression that share similar association signatures to those observed for lactation QTL, strongly implicating one or both of these genes as responsible for these effects. Using the same gene expression dataset representing 357 lactating cows, we also identified 38 novel RNA editing sites in the 3′ UTR of CSF2RB transcripts. The extent to which two of these sites were edited also appears to be genetically co-regulated with lactation QTL, highlighting a further layer of regulatory complexity that involves the CSF2RB gene. Conclusions: This locus presents a diversity of molecular and lactation QTL, likely representing multiple overlapping effects that, at a minimum, highlight the CSF2RB gene as having a causal role in these processes

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

Lactose provides an easily-digested energy source for neonate mammals, and is the primary carbohydrate in milk. Lactose is also a key component of many human food products, though compared to analyses of other milk components, the genetic control of lactose has been little studied. Here we present the first GWAS of milk lactose concentration and yield, investigated in a population of 12,000 taurine dairy cattle. We detail 27 QTL spanning these traits, and subsequently validate the effects of 26 of these loci in a separate population of 18,000 cows. We next present data implicating causative genes and variants for these QTL. Fine mapping of these regions using imputed, whole genome sequence-resolution genotypes reveals protein-coding candidate causative variants affecting the ABCG2, DGAT1, STAT5B, KCNH4, NPFFR2 and RNF214 genes. Eleven of the remaining QTL appear to be driven by regulatory effects, suggested by the presence of co-locating, co-segregating eQTL discovered using mammary RNA sequence data representing a population of 357 lactating cows. Pathway analysis of genes representing all lactose-associated loci shows significant enrichment of genes located to the endoplasmic reticulum, with functions related to ion channel activity mediated through the LRRC8C, P2RX4, KCNJ2 and ANKH genes. Together, these findings highlight novel candidate genes and variants involved in milk lactose regulation, whose impacts on facilitated and active membrane transport mechanisms reinforce the key osmo-regulatory roles of lactose in milk