In this month’s customer publication blog, both of our flagship software platforms are shown hard at work to cover many scientific investigational topics. You will get a glimpse of how VSClinical can be used to dive deeper into a specific gene associated with breast cancer and how SVS is enabling scientific discoveries in Agrigenomics and human health and wellness. Read on to see what our customers are up to and determine how Golden Helix supports them all in concrete and diverse ways. Whether you are working to ensure more positive patient outcomes or helping feed the world, a Golden Helix product can help with your scientific discoveries!

Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants in CHEK2: Findings from the Australian Breast Cancer Family Registry

Cell-cycle checkpoint kinase 2 (CHEK2) is a well-documented and established breast cancer predisposition gene and is included in routine gene panel tests for breast cancer susceptibility. Despite the gene’s known role in breast cancer risk in younger women, there is a knowledge gap for other protein-truncating variants and missense variants in CHEK2. To help fill the gap, investigators in Australia conducted a genetic screen of CHEK2 in an Australian population-based case-control-family study of breast cancer. With the help of VSClinical software, the team set out to dive deeper into the pathogenic and likely pathogenic variants in hopes of demonstrating a more precise understanding of the variants’ effects on cancer risk.  Through their results, they provided evidence that estimating age-specific cumulative risk (penetrance) is the value-added to the current CHEK2 gene panels and may bolster the ability to provide robust risk estimates that can help develop risk management strategies used by genetic counselors and clinicians to advise at-risk patients. Their findings may lead to the further study of the pathogenic variants in CHEK2 and result in a positive impact on the management options for those affected by a breast cancer diagnosis where CHEK2 is involved.

Nguyen-Dumont, T.; Dowty, J.G.; Steen, J.A.; Renault, A.-L.; Hammet, F.; Mahmoodi, M.; Theys, D.; Rewse, A.; Tsimiklis, H.; Winship, I.M.; et al. Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants in CHEK2: Findings from the Australian Breast Cancer Family Registry. Cancers 2021, 13, 1378. https://doi.org/10.3390/cancers13061378

Identification of Genomic Regions Associated with Concentrations of Milk Fat, Protein, Urea and Efficiency of Crude Protein Utilization in Grazing Dairy Cows

A research group in New Zealand applied a genome-wide association study (GWAS) to identify genes and quantitative trait loci (QTL) associated with milk fat percentage (FP), crude protein percentage (CPP), urea concentration (MU), and efficiency of crude protein utilization (ECPU: the ratio between crude protein yield in milk and dietary crude protein intake) in free-grazing versus supplementally fed dairy cows. Although many previous studies had reported candidate genes associated with FP and CPP, and a small number had identified genomic regions associated with MU, few GWAS have reported candidate genes associated with FP or CPP in New Zealand dairy cows. In addition, no published GWAS in New Zealand has identified candidate genes with MU association, and the team could find no GWAS publications on dairy cattle protein utilization efficiency worldwide. Using a single-locus approach and a multi-locus single-step Bayes C approach, the team used Snip & Variation Suite (SVS) software in their initial analysis and quality control steps for their evaluation of 490 cows from two separate dairy herds that were fed either low levels of supplemental feed and were milked one time per day or were fed high levels of supplementary feed and milked twice per day. The results of this study reported novel QTLs and genes affecting both MU and ECPU. When coupled with the results of their previous study using the same cows, genes associated with ECPU were also related to yields of milk, crude protein, and fat. The evidence supports selection for ECPU could substantially impact the economy and cow wellbeing, and the selection for reduced MU may also ensure environmental sustainability. Although the results should be validated with a larger dataset, their investigation is a positive sign for animals, humans, and the planet.

Ariyarathne, H.B.P.C.; Correa-Luna, M.; Blair, H.T.; Garrick, D.J.; Lopez-Villalobos, N. Identification of Genomic Regions Associated with Concentrations of Milk Fat, Protein, Urea and Efficiency of Crude Protein Utilization in Grazing Dairy Cows. Genes 2021, 12, 456. https://doi.org/10.3390/genes12030456

A Genome-wide Scan of Copy Number Variants in Three Iranian Indigenous River Buffaloes

Indigenous river buffalo play an important role in the agricultural landscape of Iran. Increasingly, the breeding of domesticated river buffalo is on par with domestic cattle numbers in developing countries due in part to their adaptability to harsh climate conditions, resistance to local parasites, and long productive lifespan. They are also known for their ability to convert low-quality feed to usable milk and meat production. In this study, researchers from Italy teamed with researchers from Canada and Iran to perform a whole-genome copy number variation (CNV) study of the three major Iranian river buffalo breeds using SVS software and the specialized CNV calling tool. The river buffalo’s genetic variability in the Iranian breeds has only recently been studied. Hence, the team decided to build upon this work to release the first map of CNVs for the indigenous buffalo, thus advancing the interpretation of genomic variation among the three populations studied. The authors believe more investigation will need to be done. Still, these presented results are a big step forward to understanding the unique and valuable traits that make these buffalo such an important part of agriculture in Iran.

Strillacci, M.G., Moradi-Shahrbabak, H., Davoudi, P. et al. A genome-wide scan of copy number variants in three Iranian indigenous river buffaloes. BMC Genomics 22, 305 (2021). https://doi.org/10.1186/s12864-021-07604-3

Key Genetic variants associated with Variation of Milk Oligosaccharides from Diverse Human Populations

In a recent study, a multi-national research team performed what is thought to be the first GWAS analysis on human milk oligosaccharides (HMO). HMOs are just part of the highly complex constituents that make up milk, and in human milk, they are the third most abundant solid component. They are made up of a structurally and biologically diverse group of complex digestible sugars.  Previous studies have shown that the amount of HMO in milk can be different between women and the stage of lactation, so this team set out to explore how maternal genetic variation is related to HMO profiles and concentrations. Recruiting female subjects from eight different countries and ethnicities, they used SVS software for the GWAS, which involved 400 participants.  In the results of their analysis, they hope to further the understanding of the influence of genetic polymorphisms on HMO synthesis. As such, they hope their findings will shed light on the underlying mechanisms that influence the health status of the mother and her infant.

J.E. Williams, M.K. McGuire, C.L. Meehan, et al., Key genetic variants associated with variation of Milk oligosaccharides from diverse human populations, Genomics (2021), https://doi.org/10.1016/j.ygeno.2021.04.004

I hope you enjoyed this collection of featured publications. To find the complete list of publications citing Golden Helix products, please visit our Published Articles page on our website.