Biology subjects

Harris, B. L.

Publications and source records attributed to Harris, B. L..

3 recordsLinked to original sources

bioRxiv2026

Detection and evaluation of copy number variation using both linked-read and short-read sequencing in New Zealand dairy cattle

In recent years, genetic studies have made significant progress in identifying single-nucleotide polymorphisms (SNPs) associated with cattle health and production traits. However, it is still challenging to identify and validate more complicated forms of variation, such as copy number variation (CNV) and other types of structural variation (SV). In this study, SV regions were identified using 37 New Zealand dairy cattle with linked-read sequence data. A transmission-based framework was used to validate these variants at the population scale. 62,438 putative autosomal SV regions were identified with the LongRanger pipeline following the 10x Genomics recommendations. Copy number states for these regions were subsequently estimated via a read-depth based genotyping method using CNVpytor in a population-representative cohort of 2306 animals using Illumina short-read sequencing technology. Mendelian inheritance of copy number states was assessed using linear mixed models incorporating pedigree information, and transmission levels were used to quantify the biological validity of each CNV region. Transmission levels ranged widely, with a mean of 0.5162 across all regions, where higher transmission levels were proportionally enriched for larger SVs. A total of 7218 CNV regions exhibited high transmission levels (>0.9), indicating strong evidence of inheritance. Among these, 7136 overlapped CNV regions reported in one or more public datasets, while 82 high-confidence regions represent previously unreported variants. High-transmission CNV regions tended to show clear, discrete inheritance patterns in trio families, providing the biological evidence that these CNVs are inherited within the population. Together, these results demonstrate that integrating linked-read sequencing with population-scale transmission-based validation provides a robust framework for identifying high-confidence CNV regions. This catalogue of validated CNV regions represents an important resource for downstream functional analyses and the incorporation of structural variation into genomic selection and breeding programs.

bioinformatics↗

bioRxiv2018

Multiple QTL underlie milk phenotypes at the CSF2RB locus

BackgroundBovine milk provides an important source of nutrition in much of the Western world, forming components of many food products. Over many years, artificial selection has substantially improved milk production by cows. However, the genes underlying milk production quantitative trait loci (QTL) remain relatively poorly characterised. Here, we investigate a previously-reported QTL located at the CSF2RB locus, for several milk production phenotypes, to better understand its underlying genetic and molecular causes.\n\nResultsUsing a population of 29,350 taurine dairy cattle, 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 eleven 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 the cause of 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 implicating the CSF2RB gene.\n\nConclusionsThis chromosome 5 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.

genomics↗

bioRxiv2018

Widespread cis-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 Drosophila, 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. Here, we present analyses of RNA editing in a large domestic mammal (Bos taurus), where we use whole genome and high depth RNA sequencing to discover, characterise, and conduct genetic mapping studies of novel transcript edits. Using a discovery population of nine deeply-sequenced cows, we identify 2,001 edit sites in the mammary transcriptome, the majority of which are adenosine to inosine edits (97.4%). Most sites are predicted to reside in double-stranded secondary structures (85.7%), and quantification of the rates of editing in an additional 355 cows reveals editing is negatively correlated with gene expression in the majority of cases. Genetic analyses of RNA editing and gene expression highlights 67 cis-regulated edQTL, of which seven appear to co-segregate with expression QTL effects. Trait association analyses in a separate population of 9,988 lactating cows also shows nine of the cis-edQTL coincide with at least one co-segregating lactation QTL. Together, these results enhance our understanding of RNA editing dynamics in mammals, and suggest mechanistic links by which loci may impact phenotype through RNA-editing mediated processes.

genomics↗