Biology subjects

Thomson, P. C.

Publications and source records attributed to Thomson, P. C..

3 recordsLinked to original sources

bioRxiv2022

Quantitative trait and transcriptome analysis of genetic complexity underpinning cardiac interatrial septation in mice using an advanced intercross line

Unlike single-gene mutations leading to Mendelian conditions, common human diseases are likely emergent phenomena arising from multilayer, multiscale and highly interconnected interactions. Atrial and ventricular septal defects are the most common forms of cardiac congenital anomalies in humans. Atrial septal defects (ASD) show an open communication between left and right atria postnatally, potentially resulting in serious hemodynamic consequences if untreated. A milder form of atrial septal defect, patent foramen ovale (PFO), exists in about one quarter of the human population, strongly associated with ischaemic stroke and migraine. The anatomic liabilities and genetic and molecular basis of atrial septal defects remain unclear. Here, we advance our previous analysis of atrial septal variation through quantitative trait locus (QTL) mapping of an advanced intercross line (AIL) established between the inbred QSi5 and 129T2/SvEms mouse strains, that show extremes of septal phenotypes. Analysis resolved 37 unique septal QTL with high overlap between QTL for distinct septal traits. Whole genome sequencing of parental strains identified high confidence candidate deleterious variants, including in known human congenital heart disease genes, whereas transcriptome analysis of developing septa revealed networks involving ribosome, nucleosome, mitochondrial and extracellular matrix biosynthesis underlying septal variation. Analysis of variant architecture across different gene features, including enhancers and promoters, provided evidence for involvement of non-coding as well as protein coding variants. Our study provides the first high resolution picture of genetic complexity and network liability underlying common congenital heart disease, with relevance to human ASD and PFO.

genetics↗

bioRxiv2020

A genome-wide scan for candidate lethal variants in Thoroughbred horses.

Recessive lethal variants often segregate at low frequencies in animal populations, such that two randomly selected individuals are unlikely to carry the same mutation. However, the likelihood of an individual inheriting two copies of a recessive lethal mutation is dramatically increased by inbreeding events. Such occurrences are particularly common in domestic animal populations, which are often characterised by high rates of inbreeding and low effective population sizes. To date there have been no published investigations into the presence of specific variants at high frequencies in domestic horse populations. This study aimed to identify potential recessive lethal haplotypes in the Thoroughbred horse breed, a closed population that has been selectively bred for racing performance. In this study, we scanned genotype data from Thoroughbred horses (n = 526) for adjacent single nucleotide polymorphisms (SNPs) at high heterozygote frequencies, but with a complete absence of homozygotes. Two SNPs that matched these criteria were mapped to an intronic region in the LY49B gene, indicating that a closely linked mutation may cause lethality in homozygous state. Despite a complete absence of homozygotes, almost 35% of Thoroughbreds included in these analyses were heterozygous for both SNPs. A similar loss or absence of homozygotes was observed in genotype data from other domestic horse breeds (n = 2030). Variant analysis of whole-genome sequence data (n = 90) identified two SNPs in the 3UTR region of the LY49B gene that may result in loss of function. Analysis of transcriptomic data from equine embryonic tissue revealed that LY49B is expressed in the trophoblast during placentation stage of development. In this study, a region in the LY49B gene was identified as a strong candidate for harbouring a variant causing lethality in homozygous state. These findings suggest that LY49B may have an essential, but as yet unknown function in the implantation stage of equine development. Further investigation of this region may allow for the development of a genetic test to improve fertility rates in horse populations. Identification of other lethal variants could assist in improving natural levels of fertility in horse populations. Author SummaryRecessive lethal mutations may reach high frequencies in livestock populations due to selective breeding practices, resulting in reduced fertility rates. In this study, we characterise recessive lethal mutations at high frequencies in the Thoroughbred horse population, a breed with high rates of inbreeding and low genetic diversity. We identified a haplotype in the LY49B gene that shows strong evidence of being homozygous lethal, despite having high frequencies of heterozygotes in Thoroughbreds and other domestic horse breeds. Two 3UTR variants were identified as most likely to cause loss of function in the LY49B gene, resulting in lethality. This finding provides novel insights into the potential importance of LY49B in equine development. Additionally, this study may assist with breeding strategies to improve fertility rates in the Thoroughbred and other domestic horse breeds.

bioinformatics↗

bioRxiv2020

Mesophyll conductance in two cultivars of wheat (Triticum aestivum) grown in glacial to super-elevated

Mesophyll conductance (gm) is an important factor limiting photosynthesis. However, gm response to long-term growth in variable [CO2] is not well understood, particularly in crop plants. Here, we grew two cultivars of wheat (Halberd and Cranbrook), known to differ in gm under current environmental conditions, in four [CO2] treatments: glacial (180 mol mol-1), pre-industrial (280 mol mol-1), current ambient (450 mol mol-1) and super-elevated (1000 mol mol-1) in well-watered and moderate water limitation conditions, to develop an evolutionary and future climate perspective on gm control of photosynthesis and water use efficiency (WUE). In the two wheat genotypes, gm increased with rising [CO2] from glacial to ambient [CO2], but declined at super-elevated [CO2]; however, the specific mechanism of gm response to [CO2] remains unclear. Although gm and gm/gsc (mesophyll conductance/stomatal conductance) were strongly associated with the variability of A and WUE, we found that plants with higher gm may increase A without increasing gsc, which increased WUE. These results may be useful to inform plant breeding programs and cultivar selection for Australian wheat under future environmental conditions. HighlightMesophyll conductance increased with increasing [CO2] from glacial to ambient CO2 levels, then declined at super-elevated CO2 for both well-watered and water-limited treatments. These responses of mesophyll conductance with varying [CO2] have a physiological basis.

plant biology↗