Recent publications have highlighted how Golden Helix’s VarSeq suite of products is enabling researchers and clinicians to conduct complex whole exome sequencing studies, once considered ‘out of reach,’ with ease and precision, resulting in the discovery of new biomarkers and personalized treatment options.
It is always with pride that we feature recent publications citing Golden Helix software; this month is no exception! With our VarSeq suite of products robustly supporting scaling analysis from gene panels to exomes to whole genomes, it is no wonder that complex analysis data that were once “out of reach” for most scientists and clinicians is now widely used and reported in publications across the globe. Whole exome sequencing for disease-causing mutations is of increasing importance and can help determine whether new genetic variations are associated with health conditions that will aid disease diagnosis. The featured articles below all utilized VarSeq for their whole exome sequencing studies. Read on to see how each VarSeq was incorporated as an essential part of the scientific process.
Prognosis and Personalized Medicine Prediction by Integrated whole exome and transcriptome sequencing of Hepatocellular Carcinoma
A research team in China recently published the results of a study they conducted aimed at creating a prognostic model approach to the diagnosis and treatment of hepatocellular carcinoma (HCC). HCC is the most common form of liver cancer, comprising roughly 85% of all cases. The high heterogeneity of HCC presents challenges to prognosis prediction and effective treatment options. In this study, the team utilized whole exome sequencing (WES) data from patients and identified 14 main mutant genes associated with the malignancy. Using the powerful copy number variant (CNV) tool in VarSeq, they were able to identify the main driver gene mutations and gain a better understanding of HCC biology. The team is hopeful that their study has established a quantitative map to facilitate finding biomarkers and treatment strategies for specific populations suffering from HCC, thus improving the outcomes for these patients by using precision medicine approaches.
Pseudocoloboma-like Maculopathy with Biallelic RDH12 Missense Mutations
In a case study presented in Taiwan, investigators examined seven patients from six families to determine the benefit of genetic testing in patients presenting with maculopathy related to mutations in the RDH12 gene. RDH12 itself is an enzyme known to play a role in recycling visual pigment in the photoreceptor cells. Although mutations in the RDH12 gene have been identified as causing severe childhood-onset retinal degeneration with visual impairment, this study identified individuals with relatively normal photoreceptor functions yet exhibiting macular atrophy with adolescent/adult onset, which is later in life than previously reported. For their sequence analysis, the team performed a WES evaluation using VarSeq first on three of the patients which yielded an unexpected biallelic missense variant in RDH12. Based on these initial findings, direct sequencing of the RDH12 exons was performed in the later cases presented in the study. The data in the genetic sequencing suggest that the biallelic missense mutations in RDH12 appear to be different from the typical RDH12 phenotypes. Their findings support the use of genetic testing as a crucial component of early diagnosis of maculopathy. They hope it will be beneficial for patients and may lead to the development of gene-augmented therapies in the future.
Rare Variants Found in Multiplex Families with Orofacial Clefts: Does expanding the phenotype make a difference?
In this pre-print article, a team of researchers from the United States studied several multiplex families with a history of orofacial clefts (OFCs). OFCs are a common birth defect affecting 1/1000 live births worldwide and include either cleft lip, cleft palate, or a combination of both conditions. These defects can occur on an etiological spectrum that includes Mendelian genetic causes and environmental causes. In this study, the team wanted to investigate rare coding variants within OFC families by using WES to support two complementary hypotheses: 1) that multi-plex families with inheritance patterns consistent with a Mendelian mechanism would segregate private, rare variants among affected individuals; 2) subclinical OFC phenotypes would increase support for specific inheritance patterns and those likely causal variants would segregate among individuals with either overt or subclinical phenotypes. The discussion surrounding their preliminary data would suggest that more studies will be needed to support both hypotheses but overall, the results tend to provide further evidence of the role played by rare coding variants in multiplex families with OFCs.