Whole Exome Sequencing Reveals a Novel Frameshift Deletion in Exon 7 of Wiskott-Aldrich Syndrome Causes Primary Immunodeficiency

Publish Year: 1395
نوع سند: مقاله کنفرانسی
زبان: English
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IPMCMED01_179

تاریخ نمایه سازی: 23 آذر 1397

Abstract:

Introduction: Emersion of next generation sequencing(NGS) has revolutionized our understanding of molecular basis of different diseases due to its great accuracy, high speed of sequencing and lowering the costs of previous methods. One of the most practical kinds of NGS methods is whole exome sequencing(WES) which sequences all of the exons of a genome as encoders of proteins which their defects are the main reasons of diseases. However, lots of our recent discoveries about novel genes and mutations are due to the data elicited from WES through several studies conducted for mendelian diseases, but some of the exome studies did not reached to the right fatal mutation because of wrong analyzing manners for identifying a variant, so acquisition of a right procedure for assessing data is indispensable.Methods: In this study we outlined a practical framework to discover the variants cause a primary immunodeficiency as a heterogeneous mendelian disorder. We trimmed the reads based on their quality and merged them to reduce their numbers and also make them longer for better alignment in mapping step. After mapping and variant detection, we tried to filter and annotate variants with data and information from other genome wide associations studies which reduced the variants to less than 10 numbers. The rested variants were scrutinized by checking pathways and clinical manifestation of related disease, aiming to the real causing variant. Results: We candidate a deletion in gene WAS which makes a frameshift leading its encoded protein to half of its normal size. Our claim was assayed by sanger sequencing of patient and his parents and its outcome verified our x-linked recessive mutation.Conclusion: In this study we showed that utilizing of appropriate analysis tools can accede us to the exact deleterious mutation. As targeted therapeutics and personalized medicine are becoming increasingly common in diagnosis and treatment, utilizing NGS with appropriate ways of analyzing will smoothen our path to desired goals in this field.

Authors

Majid Fathi

Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran

Arshad Hoseini

Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran