This past month has produced some very interesting and diverse publications, all of which are using the VarSeq suite of products for whole exome & whole genome sequencing strategies. This month had it all: investigations of an understudied population in pharmacogenomic testing, the first-ever find with implications for Maine coon cats, and a puzzling case with a unique family displaying unusual symptoms without an identifiable cause. There is truly something of interest for everyone this month! Read on to see the most recent situations where VarSeq helped advance genomic findings. Then call us and we will be happy to show you the power of Golden Helix’s best-in-class products!

Characterization of ADME Gene Variation in Colombian Population by Exome Sequencing

Recent advances in next-generation sequencing (NGS) technologies are being used with increasing frequency to discover molecular variations related to therapeutic efficacy and adverse drug reactions in certain individuals. These genetic profiles are underexplored in Latin-American populations, so a team of researchers in Colombia conducted a study to investigate the variability of 35 genes included in the ADME (absorption, distribution, metabolism, and excretion) core panel utilizing whole-exome sequencing. Employing VarSeq to call the variants for their study, the team used an innovative downstream bioinformatic approach which allowed them to identify common and rare variants in the ADME panel. They discovered that rare missense pharmacogenetic variants were 2.1 times more frequent in their analysis than common variants. Their findings suggest that rare loss of function (LoF) variants may be identified in 65.7% of evaluated genes. The study results provide compelling evidence that this approach would be useful for Latin American and other understudied populations to better understand their pharmacogenomic profiles while also demonstrating the utility of WES in pharmacogenomic testing. The team hopes it can also be added to clinical practice to mitigate the unexplained interindividual variability in drug response.

Silgado-Guzman DF, Angulo-Agado M, Morel A, Nino-Orrego MJ, Ruiz-Torres D-A, Contreras Bravo NC, Restrepo CM, Ortega-Recalde O and Fonseca-Mendoza DJ (2022) Characterization of ADME Gene Variation in Colombian Population by Exome Sequencing. Front. Pharmacol. 13:931531. doi: 10.3389/fphar.2022.931531

X-linked Myotubular Myopathy Associated with an MTM1 Variant in a Maine Coon Cat

In this case study involving a young Maine coon cat presenting with gait abnormalities and generalized weakness, an international team of researchers teamed up to discover a first-ever reported deleterious variant that causes a specific form of congenital myopathy in felines. The X-linked form of myotubular myopathy has been identified previously in dogs and is associated with variants in the gene encoding myotubularin (MTM1) but had not been described in cats until now. With the help of VarSeq to view, filter, and annotate their whole genome sequencing (WGS) study, the team used a variant database compiled from the 99 Lives Cat Genome Sequencing Consortium. The goal of this consortium was to build an in-depth, accessible genetic database of domestic and wild cat species that researchers could use to investigate heritable diseases. The team hopes that WGS analysis will swiftly become the standard of care in companion animals and can potentially be used in breeding programs to develop breeding plans to avoid passing heritable conditions such as X-linked myotubular myopathy to offspring. Their findings suggest that Maine coon cats, especially females intended for breeding, should be genetically tested for this deleterious disease.

Kopke, MA, Diane Shelton, G, Lyons, LA, et al. X-linked myotubular myopathy associated with an MTM1 variant in a Maine coon cat. J Vet Intern Med. 2022; 1- 6. https://doi.org/10.1111/jvim.16509

A Peculiar Family with Recurrent Self-limiting Epileptic Syndrome and Associated Developmental Disorders in Six Girls

Researchers in Italy were presented with an intriguing case involving two families exhibiting consistent social and neuropsychiatric problems in the parents and electroclinical epileptic syndrome and developmental disorders in all their offspring. In this family, two brothers married two sisters and each couple had three daughters, all of whom were affected to some degree. Due to the complexity of the exhibited conditions, unusual heritage, and the lack of an identified root cause from neurological and behavioral testing, the team turned to genetic analysis to try to determine the root cause of this family’s plight. Finding no identifiable pathogenic copy number variations in the initial testing, they used VarSeq to conduct a whole exome sequencing analysis using a targeted gene panel including 370 genes related to epilepsy and neurodevelopmental disorders with DNA from two of the daughters. The results determined that none of the selected variants appeared to be causative in the patients. After their initial familial examination, the team concluded that the phenotype of these patients had not previously been described in the literature and the root cause of the atypical presentations remains a mystery. They still highly suspect the cause is locked somewhere within the DNA of these individuals and they plan to conduct additional sequencing studies to look for causative variants in the future with the hope of including other members of each family.

Cursio I, Ronzano N, Asunis M, et al. A peculiar family with recurrent self-limited epileptic syndrome and associated developmental disorders in six girls. Epilepsy Behav Rep. 2022;19:100546. Published 2022 Apr 22. doi:10.1016/j.ebr.2022.100546