1st International and 10th National Iranian Conference on Bioinformatics

How to used Bioinformatics Tools to Disease Variant Detection?

Paper ID : 1136-ICB10

Authors:

Eskandar Taghizadeh *

Abstract:

Whole exome sequencing (WES) is a powerful tool to identifying mutations in rare genetic disorders [1]. The aim of present study was to identifying the genetic variants in a family with three affected members born from consanguineous marriages. The affected members had frequent attacks of apnea for 20–60 s with bradycardia and hypotonic; abnormal breathing patterns; fast or slow breathing (hyperpnoea), abnormal movement in eyes, distinctive facial features, ataxia and intellectual disability episodic hyperpnoea, polydactyly, syndactyly and Brain MRI showed the molar tooth sign, atrial septal defect (ASD) and ventricular septal defect (VSD) [2].
After WES with using NextSeq 500 Illumina platform with 100 million reads (100 X) the sequence reads were mapped to the hg38 genome version. GATK pipeline were used for variant calling and in the next step we used the wANNOVAR tool for variant annotation [1]. There were about 178,000 variants in raw data of proband and after this we used bioinformatics analysis for sequencing results by using standard bioinformatics software and international databases. We used filtration against benign variants such common single nucleotide polymorphisms that were previously reported in some genetic related databases as non-pathogenic or those variants with frequency more than 1%. Also we excluded variants that did not fit with the expected pattern of family pedigree. Finally, novel variants that had a deleterious effect on proteins and tissue expression were considered. We checked selected genes variants in VarElect, Phenolyzer. After this we used prediction software’s such as PolyPhen 2, SIFT, MutationTaster, FATHMM, PROVEAN and international databases including, OMIM, GeneCards and MalaCard. Finally, we found a new variant in C5ORF42 gene (c.3080A>T: p. D1027V) which is a related gene with Joubert syndrome. Confirmation tests were carried out by PCR and Sanger sequencing for identified variant in C5ORF42 gene in proband and her family members [2].

Keywords:

Keywords: Bioinformatics, Whole exome sequencing, Joubert syndrome, C5ORF42 gene

Status : Paper Accepted (Poster Presentation)