Abstract
The current study focusses screening for those pathogenic Copy Number Variations (CNVs) which are directly linked to neurogenetic disorders. CNVs are genomic structural variants, specifically those mutations having a length larger than 1000bps. Such variants may particularly be associated with a plethora of diseases, such as cancers and neurogenetic disorders. Similarly, CNVs, being the crucial parts genome, also have a number of other important roles in evolution and population diversity as well. Basically, these particular variations manifest as either deletions or duplications of sizable genomic regions. For the identification of these variants, we used Whole Exome Sequencing data to explore CNVs associated with neurological diseases in Pashtun families. To analyze the data, we employed CNVpytor to generate normalized read depth profiles for CNVs calling. The resulting variants were then visualized using the Integrative Genome Viewer (IGV). All identified CNVs were functionally annotated using tools like WANNOVAR and ClinCNV Viewer, with all statistical analyses carried out in R. From our dataset, we identified a total of 3,144 Copy Number Variants. To isolate high confidence variants, strict filtration criteria were applied, and these 3,144 CNVs were narrowed down to 245, which comprised of 93.1% deletions and 6.9% duplications. This study validates that Whole Exome Sequencing (WES) is a powerful tool for the identification of CNVs, especially those missed or pinpointed as uncertain by conventional diagnostic tests, which further enables more accurate genetic diagnosis and counselling for affected families.
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