As a provider of bioinformatics tools designed to provide insight and accelerate scientific analysis and interpretation, we love to read about ways in which researchers are using our tools such as Ingenuity® Variant Analysis™. From rare disease mutation discovery to pharmacogenomics, this tool is deployed across many sectors of scientific discovery. Here’s a quick look at some of the most recent studies we’ve found.
A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy
Sean M. Riordan, et al.
With neonatal jaundice affecting between 60-80% of newborns, healthcare professionals are careful to prevent the condition from escalating into chronic bilirubin encephalopathy (CBE) — a considerably rarer and more impactful condition when genetically based. In a recent report from Frontiers in Neuroscience, a team led by Sean M. Riordan of Children’s Mercy Hospital in Kansas City, MO, used Ingenuity Variant Analysis and QIAGEN Knowledge Base to identify causal variants in their study of significantly-narrowed SNPs. This study has not only improved medicine’s understanding of the genetic causes of CBE; it may also impact how rare disease is studied despite the lack of available GWAS or large sample sizes.
Lethal Multiple Pterygium Syndrome, the Extreme End of the RYR1 Spectrum
Ariana Kariminejad, et al.
The BMC journal Musculoskeletal Disorders recently published a study by a Tehrani team that focused on determining the cause of Lethal Multiple Pterygium Syndrome (LMPS). By conducting a range of tests (including whole exome sequencing, DNA isolation, variant annotation/selection and Sanger sequencing) on two affected fetuses, the team was able to associate LMPS with allelic defects in the excitation-contraction coupling process, and to confirm that it is an extreme sector of the spectrum related to Ryanodine receptor 1 (RYRI1) neonatal myopathy. IVA was used as a filtering strategy directed to gene candidates and focused on exonic variants where the mutation produced a missense change, stop gain or stop loss.
Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders
Jingrui Xing, et al.
Nature recently featured a study by researchers at Japan’s Nagoya University Graduate School of Medicine, which continued an existing focus on the association between genes that encode post-synaptic density (PSD) proteins and schizophrenia and autism spectrum disorders. As part of its resequencing and genetic association analysis, the team used Ingenuity Variant Analysis to identify 26 rare, non-synonymous variants specific to carriers of schizophrenia and autism spectrum disorders. They then completed an association analysis in a larger sample set for three of those variants. The resulting investigation suggested that rare PSD mutations may increase susceptibility to schizophrenia and autism spectrum disorders.
Genomic Architecture of Inflammatory Bowel Disease in Five Families with Multiple Affected Individuals
Anna B. Stittrich, et al.
NIH’s Human Genome Variation journal ran the results of a study on families with multiple inflammatory bowel disease (IBD)-affected individuals from a team led by scientists at Seattle’s Institute of Systems Biology. Moving beyond existing GWAS which indicate a strong genetic risk factor for IBD, the researchers used whole genome sequencing to look at 38 individuals from five families. They used Ingenuity Variant Analysis to identify variants, and QIAGEN Knowledge Base to filter the variants and identify commons factors, including rare risk variants that are shared among family members and substantially affect disease development. While ultimately their findings could not point to only rare variants as significant causal factors, they did uncover the possibility that very-early-onset IBD might be an entirely new disease entity, separate from classical IBD.
Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice
Kristóf Árvai, et al.
Researchers from Budapest’s Semmelweis University used IVA for variant interpretation in their recent report published in the NIH’s Scientific Reports. Focused on Osteogenesis imperfecta (also known as brittle-bone disease) and led by Kristóf Árvai, the team used NGS to determine the most significant genetic variants of the disease. Their resulting data allowed them to assert that clinicians could indeed use NGS to supplement diagnostic process with molecular genetic data—particularly when a disease has complex genetic background and non-recurrent mutation hot spots.
Ingenuity Variant Analysis is providing significant scientific insight around the world. We’d love to hear how you’re using it – so send us an email if you’d like to share your research, or request a trial if you’re not yet using Ingenuity Variant