September’s published articles citing Golden Helix software serve as a testament to our product’s broad applications and utility in NGS data analysis. We are always proud of our customers and the contributions they make to advancing scientific discovery and are grateful to be included in their research. This month, we were treated to publications from all over the globe showing a broad range of research topics and scientific approaches to presenting their findings. Our flagship products, SNP & Variation Suite (SVS) and VarSeq are mentioned in the scientific investigations I have summarized below. They are only a tiny sampling of the total number of published works that cited Golden Helix this month! As always, if you would like to read the publication in its entirety, just click on the title to be redirected to the full text. Please enjoy them, and I hope you find them as inspiring as I have!
Researchers in Taiwan pooled efforts to conduct a study to pinpoint the genetic factors associated with drinking behavior in an Asian population. Using SVS software for their GWAS, the investigation focused on the population of a small town on the northern coast of Taiwan. The town has a rich history of diverse colonization and was a pivotal harbor town connecting the East and Southeast Asian regions; therefore, the population of this community is primarily of Chinese ancestry. The team first assessed participants for alcohol consumption using the original Alcohol Use Disorder Identification Test (AUDIT) score developed by the World Health Organization. While the genetic influences of habitual drinking behaviors have been widely studied, the data supported the association of an Asian-specific genomic variant in the ALDH2 gene, which plays a part in the oxidative pathway of alcohol metabolism. The team took their data a step further to estimate the age of the associated allele. Click on the title of this publication to read the whole story. It is fascinating!
Lin, C., Chien, R., Chen, L., Huang, T., Shyu, Y., Yeh, C., & Liang, K. (2021). The Aldehyde Dehydrogenase ALDH2*2 Allele, Associated with Alcohol Drinking Behavior, Dates Back to Prehistoric Times. Biomolecules, 11(9), 1376. https://doi.org/10.3390/biom11091376
Targeted Molecular Characterization of External Auditory Canal Squamous Cell Carcinomas
Squamous cell carcinomas (SCC) of the external auditory canal (EAC) arise in non-ultraviolet-exposed areas of the head and neck. They are often locally aggressive and can metastasize to lymph nodes or distant sites. Although much is known about the genomic alterations of cutaneous SCC, the mutational profiles of EAC SCC are not well understood. The goal of this study was to discover potentially targetable genomic alterations of this rare type of SCC. The team utilized seven patients that met their inclusion criteria in their targeted exome sequencing investigation, which was performed while incorporating VarSeq software and a custom gene panel. The team sees their data as an initial step toward identifying driver mutations and may potentially point to molecular treatment targets.
Basura, G., Smith, J., Ellsperman, S., Bhangale, A., & Brenner, J. (2021). Targeted molecular characterization of external auditory canal squamous cell carcinomas. Laryngoscope Investigative Otolaryngology. https://doi.org/10.1002/lio2.654
In this pre-print paper, researchers from Indiana, Texas, and Ohio built upon previous findings to further define the role the COQ8B gene plays in the severity of thoracic aortic aneurysms (TAA). Recent epidemiological data have indicated that approximately 12,000 deaths occur in the United States annually. Since the disease is sometimes difficult to identify and the progression leads to life-threatening thoracic aortic dissections, knowing the risk of developing TAA would greatly benefit patient management. The genetic factors that control the development and severity of TAA are not fully understood. Hence, the team focused on how variants in the COQ8B gene might affect aortic smooth muscle cells that are central to the pathogenesis of TAA. Using SVS software to call variants in their whole exome examination of the COQ8B SNP rs385452, their findings indicate that metabolic dysfunction is common to TAA in diverse genetic and developmental contexts. The team hopes their findings may lead to improved risk stratification and to more tailored aortopathy management.
Landis BJ, Lai D, Guo D-C, Corvera JS, Idrees MT, Stadler HW, Cuevas C, Needler GU, Vujakovich CE, Milewicz DM, Hinton RB, Ware SM, Identification of a common polymorphism in COQ8B acting as a modifier of thoracic aortic aneurysm severity., Human Genetics and Genomics Advances (2021), doi: https://doi.org/10.1016/j.xhgg.2021.100057.
A team of researchers led by investigators from Canada recently evaluated members of a large family that presented with varying forms of epilepsy syndromes. The phenotypes in the study group ranged from developmental and epileptic encephalopathy to mild focal epilepsy without cognitive regression and not consistent with sleep-related hypermotor epilepsy. Their methodology included a combination of gene panel analysis and exome sequencing. Using VSClinical for the variant calling and classification steps, the team demonstrated that KCNT1 variants can be associated with a broader phenotypic spectrum than previously observed. Their data make a case for including identified KCNT1 variants in the assessment of patients with mild focal epilepsy and more severe epileptic syndromes. They hope it will lead to a precision medicine treatment for those harboring these variants.
Cherian, C., Appendino, J., Ashtiani, S., Federico, P., Molnar, C., & Kerr, M. et al. (2021). The phenotypic spectrum of KCNT1: a new family with variable epilepsy syndromes including mild focal epilepsy. Journal Of Neurology. https://doi.org/10.1007/s00415-021-10808-y
Juvenile onset open-angle glaucoma (JOAG) and primary congenital glaucoma (PCG) are both types of glaucoma, with the former affecting children as young as three years of age and the latter being present at birth. To better understand the genetic root causes of these diseases, a research team from India had a rare opportunity to study a case where monozygotic twins were diagnosed with PCG. The team utilized VarSeq software to perform a family-based whole exome sequencing investigation which uncovered a novel missense mutation in the PLOD2 gene. Their findings indicate that this gene may play a key role in some JOAG and PCG instances, and further research is needed to determine the cause-and-effect relationship of this gene with these rare juvenile glaucoma diseases.
Gupta, Viney; Somarajan, Bindu I; Kaur, Gagandeep1; Gupta, Shikha; Singh, Renu; Pradhan, Dibyabhaba2; Singh, Harpreet2; Kaur, Punit3; Sharma, Anshul5; Chawla, Bindia4; Pahuja, Anisha4; Ramachandran, Rajesh4; Sharma, Arundhati5 Exome sequencing identifies procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 mutations in primary congenital and juvenile glaucoma, Indian Journal of Ophthalmology: October 2021 – Volume 69 – Issue 10 – p 2710-2716 doi: 10.4103/ijo.IJO_1750_21