Recent Customer Publications – April 2020

         April 30, 2020

Scientific investigations and genetic discoveries continue to happen in several diverse areas even while our world is currently consumed by the greatest health challenge of our era. Below are a few examples of some of the great work being done in the fields of human medicine, ecology, and breed conservation of animal species. As always, we are so very proud to be a part of such a vast range of studies and we thank those who persevere to advance our knowledge in so many areas. Remember to click on the link to access the articles in their entirety and see how SVS, VarSeq, and GenomeBrowse are working for others!

Quantitative Proteomic Landscape of Metaplastic Breast Carcinoma Pathological Subtypes and Their Relationship to Triple-negative Tumors

Triple-negative breast cancer (TNBC) comprises about 10-20% of breast cancers and are characterized by the lack of estrogen/progesterone receptors, and excess HER2 protein. As a result, TNBCs do not respond to hormonal therapies or medicines that target HER2 protein receptors. The most lethal subtype of TNBC is Metaplastic breast carcinomas (MBC) and this subtype accounts for 0.2-5% of all breast cancers. Researchers at the University of Michigan conducted a study using a combination of human tissue samples and samples from a specific strain of knockout mice in order to better understand the protein profiles that determine MBC histological subtypes and develop a suitable animal model. Initial analysis methods pinpointed specific pathways potentially operating in MBC compared to TNBC for further investigation. The team then focused on the MBC subtype-specific mutational signatures to perform their whole exome sequencing (WES) analysis. Using VarSeq to annotate the variants in the WES portion of the study, the data ultimately supports what appears to be a new approach to investigating the proteomic landscape of MBC as it relates to TNBC. In addition, the team was able to present evidence to support the use of this mouse model to test new treatments and further investigations of the mechanisms of MBC. They are hopeful their study will provide an opportunity to impact precision therapies to extend the lives of the women who are afflicted by this aggressive form of breast cancer.

University of Michigan / Published in Nature Communications

Added Value of Clinical Sequencing: WGS-based Profiling of Pharmacogenes

Researchers in Switzerland recently set out to evaluate the value of short-read whole genome sequencing (WGS) when applied to pharmacogenetic (PGx) testing. Current pre-emptive PGx testing is most often performed using microarrays or targeted gene panels which are testing for common or known PGx variants. In their study, the team expanded testing to utilize a WGS-based approach which offers the added benefit of also providing genetic testing for Mendelian diseases along with PGx profiling. With this approach, the use of WGS enables the detection of rare/novel PGx variants not currently detected with standard WES-based PGx testing. With VarSeq employed to annotate and filter their WGS data, the team has presented evidence that replacing WES analysis with short-read WGS offers a beneficial comprehensive approach. The team suggests that for the best possible pharmacogenetically-guided treatment recommendations for individual patients, the use of genome-wide profiling can expand the targeted profiling of known PGx variants to include all pharmacogenes, thus demonstrating true precision medicine.

Gabor Matyas, Sylvan Caspar & Colleagues, Foundation for People with Rare Diseases (Switzerland) / Published in the International Journal of Molecular Sciences

Mixed Ancestry from Wild and Domestic Lineages Contributes to the Rapid Expansion of Invasive Feral Swine

An international team of investigators from the US, Netherlands, and Brazil conducted an ancestry analysis of invasive feral swine to better understand the introduction pathways, sources of newly emergent populations, and the current processes contributing to the ongoing invasion. Invasive alien species (such as the feral swine found in many parts of the US) are currently one of the greatest threats to biodiversity and as the problem grows, it comes at great socio-economic, health, and ecological cost around the world. The team’s investigation took them to locations within the US where populations of feral swine have been rapidly expanding to try to find the answer to what contributes to this invasion. Using SVS software as they took a deep dive into the ancestry of these different swine populations, they were able to identify several key factors as to why this particular species of invader has experienced a virtual population explosion over the past 30 years. Their discoveries may help in understanding the direct linkages between genotypes and phenotypes, and the team hopes their study may serve as a model to describe the evolution of invasive populations.   

Timothy Smyser & Colleagues, National Wildlife Research Center / Published in Molecular Ecology

The German Shorthair Pointer Dog Breed (Canis lupus familiaris): Genomic Inbreeding and Variability

SVS software was used by a team of Italian researchers as they investigated the genetic variability of the modern German Shorthair Pointer (GSHP), a popular breed of hunting and companion dogs. To explore the genomic architecture and analyze inbreeding levels from both the genomic and genealogic perspective, the team used a total of 34 dogs who were as unrelated as possible: 24 were dogs from Italy and 10 were dogs from the US. Adding to the traditional approach of calculating the inbreeding coefficient (IC) using pedigree information, they introduced molecular genetics to create a genomic IC, using runs of homozygosity (ROH). SVS was used to perform the Principal component analysis (PCA) and was also used to detect the ROH, which were then used to create the genomic IC. The team hopes their discovery and methods will make a strong case for integrating both genealogical and molecular information as a standard of investigation to protect and conserve animal populations that are susceptible to the deleterious effects of inbreeding.

Alessandro Bagnato & Colleagues, University of Milan / Published in Animals

Dynamics of Genomic Architecture during Composite Breed Development in Cattle

Along the same lines as the previous publication focused on GSHP’s, investigators from the US and Brazil teamed up to study the genomic architecture of beef cattle to determine the genetic stability of composite breed development. The team used a composite breed of American Brangus cattle created by crossing breeds from the two subspecies of domesticated cattle: Bos taurus indicus (Brahman in this case) and Bos taurus taurus (Angus in this case). Early breeders were looking for a desirable beef-type animal that would retain the Brahman’s ability to adapt to adverse environmental conditions while adding the superior carcass qualities the Angus breed is known to exhibit. First established as a recognized composite breed in 1949, the data from nine generations of Brangus cattle were used in this study to determine if the breed in general still represents the intent of the International Brangus Breeders Association’s goal of making the hybrid 62.5% Angus and 37.5% Brahman. Using SVS software for the PCA portion of the study and GenomeBrowse to identify the gene regions of founder deviation, they were able to demonstrate that there was a higher proportion of Angus then expected (70.4% vs. the goal of 62.5%) in more recent generations. The results suggest that in order to preserve and maintain Brangus as originally intended, breeders should be aware of this deviation if they intend to retain the Brahman component in the breed. The addition of genetic architecture to the genealogical data would likely benefit breeders during the selection process.

El Hamidi Hay (USDA), Samuel Paiva (Embrapa) & Colleagues / Published in Animal Genetics

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.

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