Precision tools are paramount for unlocking groundbreaking discoveries in the rapidly evolving field of genetic research. We have consistently paved the way with VarSeq—an all-encompassing solution tailored for genomics professionals. This sophisticated tool not only simplifies the complexity of genomic data but also amplifies its potential to drive significant advancements in medical research and personalized care. From aiding pediatric nephrology in Bulgaria to uncovering the genetic underpinnings of diseases like autism in Pakistan and Parkinson’s influenced by environmental factors, our customers are at the forefront of translating genomic data into actionable insights.
Introducing Exome Sequencing as Part of the Diagnostic Algorithm for Pediatric Nephrology Patients in Bulgaria: A Single-Center Experience
Introduction: In pediatric kidney patients, where clinical presentation is often not fully developed, and renal biopsy is too risky or inconclusive, it may be difficult to establish the underlying pathology. In cases such as these, genetic diagnosis may be used to guide treatment, prognosis, and counseling. Given the large number of genes involved in kidney disease, introducing next-generation sequencing with extended gene panels as part of the diagnostic algorithm presents a viable solution. Methods: A cohort of 87 consecutive independent cases (83 children and 4 terminated pregnancies) with renal disease was recruited. Exome sequencing with MiSeq or NovaSeq 6000 (Illumina) platforms and analysis of extended gene panels were used for genetic testing. Results: Depending on the presenting pathology, the cases were grouped as patients with glomerular disease, ciliopathies, congenital anomalies, renal electrolyte imbalances, and chronic/acute kidney disease. The overall diagnostic yield was approximately 42% (37 out of 87), with most disease-causing mutations found in COL4A3, COL4A4, COL4A5, and PKHD1 genes. A change or clarification of preliminary diagnosis or adjustment of initial treatment plan based on the results of the genetic testing was made for approximately one-third of the children with meaningful genetic findings (11 out of 37). Discussion: Our results prove the value of targeted exome sequencing as a non-invasive, versatile, and reliable diagnostic tool for pediatric renal disease patients. Providing genetic diagnosis will help for a better understanding of disease etiology and will give the basis for optimal clinical management and insightful genetic counseling.
Biallelic variants identified in 36 Pakistani families and trios with autism spectrum disorder
With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan. Microarray genotyping followed by homozygosity mapping, copy number variation analysis, and whole exome sequencing were used to identify candidate. Given the high levels of consanguineous marriages among these families, autosomal recessively inherited variants were prioritized, however de novo/dominant and X-linked variants were also identified. The selected variants were validated using Sanger sequencing. Here we report the identification of sixteen rare or novel coding variants in fifteen genes (ARAP1, CDKL5, CSMD2, EFCAB12, EIF3H, GML, NEDD4, PDZD4, POLR3G, SLC35A2, TMEM214, TMEM232, TRANK1, TTC19, and ZNF292) in affected members in eight of the families, including ten homozygous variants in four families (nine missense, one loss of function). Three heterozygous de novo mutations were also identified (in ARAP1, CSMD2, and NEDD4), and variants in known X-linked neurodevelopmental disorder genes CDKL5 and SLC35A2. The current study offers information on the genetic variability associated with ASD in Pakistan, and demonstrates a marked enrichment for biallelic variants over that reported in outbreeding populations. This information will be useful for improving approaches for studying ASD in populations where endogamy is commonly practiced.
Lysosomal genes contribute to Parkinson’s disease near agriculture with high intensity pesticide use
Parkinson’s disease (PD), the second most common neurodegenerative disorder, develops sporadically, likely through a combination of polygenic and environmental factors. Previous studies associate pesticide exposure and genes involved in lysosomal function with PD risk. We evaluated the frequency of variants in lysosomal function genes among patients from the Parkinson’s, Environment, and Genes (PEG) study with ambient pesticide exposure from agricultural sources. 757 PD patients, primarily of White European/non-Hispanic ancestry (75%), were screened for variants in 85 genes using a custom amplicon panel. Variant enrichment was calculated against the Genome Aggregation Database (gnomAD). Enriched exonic variants were prioritized by exposure to a cluster of pesticides used on cotton and severity of disease progression in a subset of 386 patients subdivided by race/ethnicity. Gene enrichment analysis identified 36 variants in 26 genes in PEG PD patients. Twelve of the identified genes (12/26, 46%) had multiple enriched variants and/or a single enriched variant present in multiple individuals, representing 61% (22/36) of the observed variation in the cohort. The majority of enriched variants (26/36, 72%) were found in genes contributing to lysosomal function, particularly autophagy, and were bioinformatically deemed functionally deleterious (31/36, 86%). We conclude that, in this study, variants in genes associated with lysosomal function, notably autophagy, were enriched in PD patients exposed to agricultural pesticides suggesting that altered lysosomal function may generate an underlying susceptibility for developing PD with pesticide exposure. Further study of gene-environment interactions targeting lysosomal function may improve understanding of PD risk in individuals exposed to pesticides.
As we’ve explored through various global case studies, our customers are making remarkable strides in the field of genomics with the help of VarSeq. Whether it’s diagnosing complex pediatric kidney diseases, identifying genetic variants in autism, or understanding the environmental impacts on Parkinson’s disease, VarSeq stands out as a vital tool in the genomics toolkit. This technology not only fosters a deeper understanding of genetic disorders but also enhances the precision of medical interventions, propelling us closer to the era of truly personalized medicine. By embracing such powerful genomic solutions, researchers and clinicians worldwide are better equipped to address the unique challenges of their specializations, ultimately improving patient outcomes and advancing our collective knowledge.