Customer Publications February 2022

         February 28, 2022

VarSeq software again takes center stage in our recent publications for February. It is our great honor to be a part of the groundbreaking discoveries highlighted below as well as the many others too numerous to include in this blog post! We are happy to contribute to scientific findings from all our analysis platforms, but we are especially proud of our VarSeq suite of products. Our customers love its scalability, intuitive & repeatable workflows, and rich visualization, compliments of GenomeBrowse. The ability to add modules of functionality such as VSClinical for clinical reporting & automated variant classification as well as our industry leading CNV analysis module are also reasons most cited as helping customers make the decision to become part of our Golden Helix family. Please read on to see just a few examples of how VarSeq can help you with your quest to enable precision medicine!

Family-based Whole-exome Sequencing Identifies Rare Variants Potentially Related to Cutaneous Melanoma Predisposition in Brazilian Melanoma-prone Families

A team of researchers set out to identify novel genomic variants related to melanoma predisposition beyond the known inherited genomic risk. Selecting five Brazilian families with at least two cases of cutaneous melanoma, they analyzed a total of ten probands that were negative for common causal inherited genomic variants. This approach allowed them to focus their analysis on additional novel variants that could be detected in this specific study population. Using VarSeq for variant prioritization for their whole exome sequencing (WES) analysis, the team discovered several novel variants contributing to melanoma susceptibility. The team hopes the discovery of novel germline variants in their study will provide new insights into melanoma predispositions in Brazilian families. This pilot study represents the first WES data from melanoma-prone families in a highly admixed population. Their data underscores the putative role of novel genes for melanoma risk which can be useful in designing future studies.

Fidalgo F, Torrezan GT, Sá BCSd, Barros BDdF, Moredo LF, et al. (2022) Family-based whole-exome sequencing identifies rare variants potentially related to cutaneous melanoma predisposition in Brazilian melanoma-prone families. PLOS ONE 17(1): e0262419.

The Design and Rationale of the Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of Hypercholesterolemia (ACCURATE) Study

Principle investigators in Canada have designed a first of its kind clinical trial to use as a basis for utilizing genetic testing to analyze potential germline causes of familial hypercholesterolemia (FH) in the acute cardiac care setting. FH is the most common inherited cardiovascular disorder, yet the condition is still highly underdiagnosed and undertreated worldwide. An estimated 99% of FH patients worldwide remain undiagnosed which limits the ability to optimally treat them. Although several commonly used diagnostic criteria are already being employed worldwide and clinical practice guidelines recommend using genetic testing to facilitate the diagnosis of FH, it is still unused and/or unavailable in many areas. The study this team is proposing would focus on patients with acute coronary syndrome (ACS) and the genetic analysis would focus on the LDLR, APOB & PCSK9 genes, which are known causative genetic factors for FH. They plan to use VarSeq’s VSClinical module along with the VS-CNV module for the upcoming study. Once completed, the study will answer the question of whether clinical implementation of genetic testing within the acute cardiac care setting improves the early diagnosis and treatment of FH. The team has also outlined the future of sub-studies that will be conducted to add to evidence gathered from this primary study to support implementing genetic testing as a standard of care for ACS patients.

Junran J. Peng, Navid Saleh, Thomas M. Roston, Adam Kramer, Lubomira Cemakova, G.B. John Mancini, Christopher B. Fordyce, Liam R. Brunham, The design and rationale of the Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) study, American Heart Journal Plus: Cardiology Research and Practice, 2022, 100097, ISSN 2666-6022,

Human Germline Biallelic Complete NFAT1 Deficiency Causes the Triad of Progressive Join Contractures, Osteochondromas, and Susceptibility to B Cell Malignancy

In this preprint article from Canada, researchers report the first human subject to be identified as having a complete deficiency of nuclear factor of activated T cells 1 (NFAT1). NFAT is a family of transcription factors shown to play an important role in immune response, with one or more NFAT family members being expressed in most cells of the immune system. Scientific insights into the complex interactions between the NFAT family and immune responses in humans have grown substantially in recent years. However, the specific functions of each individual NFAT protein are still not completely understood. What is known is the role they play in T cell activation which has led them to be targeted for developing immune modulating drugs for treating autoimmune diseases. These drugs also cause some serious adverse side effects because they inhibit all members of the NFAT family and not just proteins that are causative of the specific disease being treated. It is critical to learn more about the role of each NAFT member if new, less damaging drugs are to be successfully identified. Since findings from preclinical studies of NAFTs using murine models do not translate to the human system, the team took the opportunity to study a rare individual who carries a damaging germline variant in genes encoding NFAT1. With the help of VarSeq in the trio whole exome sequencing (WES) portion of their investigation, the team performed a comprehensive clinical, immunological, biochemical and transcriptional workup which identified this particular individual to be the first reported case of complete NFAT1 deficiency in a human subject. They suggest their findings may serve as a model for implementing additional diagnostic workups for patients exhibiting similar symptoms thus identifying others who may also suffer from complete NFAT1 deficiency. The information gleaned from this study has provided new insight into the role of NFAT1 in the human musculoskeletal and immune systems. They hope their findings will help to unlock the secrets to how this member of the NFAT family works with… or against the human immune system.

Human germline biallelic complete NFAT1 deficiency causes the triad of progressive joint contractures, osteochondromas, and susceptibility to B cell malignancy Mehul Sharma, Maggie P. Fu, Henry Y. Lu, Ashish A. Sharma, Bhavi P. Modi, Christina Michalski, Susan Lin, Joshua Dalmann, Areesha Salman, Kate L. Del Bel, Meriam Waqas, Jefferson Terry, Audi Setiadi, Pascal M. Lavoie, Wyeth W. Wasserman, Jill Mwenifumbo, Michael S. Kobor, Anna F. Lee, Anna Lehman, Sylvia Cheng, Anthony Cooper, Millan S. Patel, Stuart E. Turvey medRxiv 2022.01.30.22269378; doi:

Thank you for reading and if you would like to explore more of the publications in which Golden Helix has been cited, feel free to visit our website and search for “Published Articles”. We are pleased to share all the inspirational work over the past 2 decades on our website!

Leave a Reply

Your email address will not be published. Required fields are marked *