eQTL-Detect: nextflow-based pipeline for eQTL detection in modular format with sharable and parallelizable scripts.

Bioinformatic pipelines are becoming increasingly complex with the ever-accumulating amount of Next-generation sequencing (NGS) data. Their orchestration is difficult with a simple Bash script, but bioinformatics workflow managers such as Nextflow provide a framework to overcome respective problems. This study used Nextflow to develop a bioinformatic pipeline for detecting expression quantitative trait loci (eQTL) using a DSL2 Nextflow modular syntax, to enable sharing the huge demand for computing power as well as data access limitation across different partners often associated with eQTL studies.

Mitochondrial sequence variants: testing imputation accuracy and their association with dairy cattle milk traits.

Background: Mitochondrial genomes differ from the nuclear genome and in humans it is known that mitochondrial variants contribute to genetic disorders. Prior to genomics, some livestock studies assessed the role of the mitochondrial genome but these were limited and inconclusive. Modern genome sequencing provides an opportunity to re-evaluate the potential impact of mitochondrial variation on livestock traits.

Meta-analysis of six dairy cattle breeds reveals biologically relevant candidate genes for mastitis resistance.

Background: Mastitis is a disease that incurs significant costs in the dairy industry. A promising approach to mitigate its negative effects is to genetically improve the resistance of dairy cattle to mastitis. A meta-analysis of genome-wide association studies (GWAS) across multiple breeds for clinical mastitis (CM) and its indicator trait, somatic cell score (SCS), is a powerful method to identify functional genetic variants that impact mastitis resistance.

Allele-specific binding variants causing ChIP-seq peak height of histone modification are not enriched in expression QTL annotations.

Background: Genome sequence variants affecting complex traits (quantitative trait loci, QTL) are enriched in functional regions of the genome, such as those marked by certain histone modifications. These variants are believed to influence gene expression. However, due to the linkage disequilibrium among nearby variants, pinpointing the precise location of QTL is challenging.

Genome-wide association and expression quantitative trait loci in cattle reveals common genes regulating mammalian fertility.

Most genetic variants associated with fertility in mammals fall in non-coding regions of the genome and it is unclear how these variants affect fertility. Here we use genome-wide association summary statistics for Heifer puberty (pubertal or not at 600 days) from 27,707 Bos indicus, Bos taurus and crossbred cattle; multi-trait GWAS signals from 2119 indicine cattle for four fertility traits, including days to calving, age at first calving, pregnancy status, and foetus age in weeks (assessed by rectal palpation of the foetus); and expression quantitative trait locus for whole blood from 489 indicine cattle, to identify 87 putatively functional genes affecting cattle fertility. Our analysis reveals a significant overlap between the set of cattle and previously reported human fertility-related genes, impling the existence of a shared pool of genes that regulate fertility in mammals.

Using expression data to fine map QTL associated with fertility in dairy cattle.

Background: Female fertility is an important trait in dairy cattle. Identifying putative causal variants associated with fertility may help to improve the accuracy of genomic prediction of fertility. Combining expression data (eQTL) of genes, exons, gene splicing and allele specific expression is a promising approach to fine map QTL to get closer to the causal mutations.

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.

Ancestral alleles defined for 70 million cattle variants using a population-based likelihood ratio test.

Background: The study of ancestral alleles provides insights into the evolutionary history, selection, and genetic structures of a population. In cattle, ancestral alleles are widely used in genetic analyses, including the detection of signatures of selection, determination of breed ancestry, and identification of admixture. Having a comprehensive list of ancestral alleles is expected to improve the accuracy of these genetic analyses.

Allele specific binding of histone modifications and a transcription factor does not predict allele specific expression in correlated ChIP-seq peak-exon pairs.

Allele specific expression (ASE) is widespread in many species including cows. Therefore, regulatory regions which control gene expression should show cis-regulatory variation which mirrors this differential expression within the animal. ChIP-seq peaks for histone modifications and transcription factors measure activity at functional regions and the height of some peaks have been shown to correlate across tissues with the expression of particular genes, suggesting these peaks are putative regulatory regions.

The Bovine Pangenome Consortium: democratizing production and accessibility of genome assemblies for global cattle breeds and other bovine species.

The Bovine Pangenome Consortium (BPC) is an international collaboration dedicated to the assembly of cattle genomes to develop a more complete representation of cattle genomic diversity. The goal of the BPC is to provide genome assemblies and a community-agreed pangenome representation to replace breed-specific reference assemblies for cattle genomics. The BPC invites partners sharing our vision to participate in the production of these assemblies and the development of a common, community-approved, pangenome reference as a public resource for the research community ( https://bovinepangenome.

In it for the long run: perspectives on exploiting long-read sequencing in livestock for population scale studies of structural variants.

Studies have demonstrated that structural variants (SV) play a substantial role in the evolution of species and have an impact on Mendelian traits in the genome. However, unlike small variants (< 50 bp), it has been challenging to accurately identify and genotype SV at the population scale using short-read sequencing. Long-read sequencing technologies are becoming competitively priced and can address several of the disadvantages of short-read sequencing for the discovery and genotyping of SV.

Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle.

Background: Causal variants for complex traits, such as eQTL are often found in non-coding regions of the genome, where they are hypothesised to influence phenotypes by regulating gene expression. Many regulatory regions are marked by histone modifications, which can be assayed by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Sequence reads from ChIP-seq form peaks at putative regulatory regions, which may reflect the amount of regulatory activity at this region.

Recovery of mitogenomes from whole genome sequences to infer maternal diversity in 1883 modern taurine and indicine cattle.

Maternal diversity based on a sub-region of mitochondrial genome or variants were commonly used to understand past demographic events in livestock. Additionally, there is growing evidence of direct association of mitochondrial genetic variants with a range of phenotypes. Therefore, this study used complete bovine mitogenomes from a large sequence database to explore the full spectrum of maternal diversity.

Mutant alleles differentially shape fitness and other complex traits in cattle.

Mutant alleles (MAs) that have been classically recognised have large effects on phenotype and tend to be deleterious to traits and fitness. Is this the case for mutations with small effects? We infer MAs for 8 million sequence variants in 113k cattle and quantify the effects of MA on 37 complex traits. Heterozygosity for variants at genomic sites conserved across 100 vertebrate species increase fertility, stature, and milk production, positively associating these traits with fitness.

Corrigendum: Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues.

[This corrects the article DOI: 10.3389/fgene.2021.

Neurology podcast utilization during the COVID-19 pandemic.

Background: As medical education shifted to a virtual environment during the early coronavirus disease 2019 (COVID-19) pandemic, we evaluated how neurology podcasting may have been utilized during this period, and which features of podcasts have been more highly sought by a medical audience.

Methods: We conducted a retrospective analysis of neurology-themed blogs and/or podcasts between April 2019 and May 2020. Programs were eligible if they reported mean monthly downloads > 2000, were affiliated with an academic society, or offered continuing medical education credit.

Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues.

Genetic variants which affect complex traits (causal variants) are thought to be found in functional regions of the genome. Identifying causal variants would be useful for predicting complex trait phenotypes in dairy cows, however, functional regions are poorly annotated in the bovine genome. Functional regions can be identified on a genome-wide scale by assaying for post-translational modifications to histone proteins (histone modifications) and proteins interacting with the genome (e.

Evolution of tissue and developmental specificity of transcription start sites in Bos taurus indicus.

To further the understanding of the evolution of transcriptional regulation, we profiled genome-wide transcriptional start sites (TSSs) in two sub-species, Bos taurus taurus and Bos taurus indicus, that diverged approximately 500,000 years ago. Evolutionary and developmental-stage differences in TSSs were detected across the sub-species, including translocation of dominant TSS and changes in TSS distribution. The 16% of all SNPs located in significant differentially used TSS clusters across sub-species had significant shifts in allele frequency (472 SNPs), indicating they may have been subject to selection.

Education Research: NeuroBytes: A New Rapid, High-Yield e-Learning Platform for Continuing Professional Development in Neurology.

Objective: To determine whether NeuroBytes is a helpful e-Learning tool in neurology through usage, viewer type, estimated time and cost of development, and postcourse survey responses.

Background: A sustainable Continuing Professional Development (CPD) system is vital in neurology due to the field's expanding therapeutic options and vulnerable patient populations. In an effort to offer concise, evidence-based updates to a wide range of neurology professionals, the American Academy of Neurology (AAN) launched NeuroBytes in 2018.