Molecular classification of blood and bleeding disorder genes

Batoul Baz; Mohamed Abouelhoda; Tarek Owaidah; Majed Dasouki; Dorota Monies; Nada Al Tassan

doi:10.1038/s41525-021-00228-2

Molecular classification of blood and bleeding disorder genes

NPJ Genom Med. 2021 Jul 16;6(1):62. doi: 10.1038/s41525-021-00228-2.

Authors

Batoul Baz^#^{1

2}, Mohamed Abouelhoda^#^{1

2

3}, Tarek Owaidah⁴, Majed Dasouki², Dorota Monies^#^{1

2}, Nada Al Tassan^{5

6}

Affiliations

¹ Saudi Human Genome Program, National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
² Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
³ Systems and Biomedical Engineering Department, Faculty of Engineering, Cairo University, Giza, Egypt.
⁴ Department of Pathology & Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
⁵ Saudi Human Genome Program, National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. naltassan@kfshrc.edu.sa.
⁶ Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. naltassan@kfshrc.edu.sa.

^# Contributed equally.

Abstract

The advances and development of sequencing techniques and data analysis resulted in a pool of informative genetic data, that can be analyzed for informing decision making in designing national screening, prevention programs, and molecular diagnostic tests. The accumulation of molecular data from different populations widen the scope of utilization of this information. Bleeding disorders are a heterogeneous group of clinically overlapping disorders. We analyzed the targeted sequencing data from ~1285 Saudi individuals in 17 blood and bleeding disorders genes, to determine the frequency of mutations and variants. We used a replication set of ~5000 local exomes to validate pathogenicity and determine allele frequencies. We identified a total of 821 variants, of these 98 were listed in HGMD as disease related variants and 140 were novel variants. The majority of variants were present in VWF, followed by F5, F8, and G6PD genes, while FGG, FGB, and HBA1 had the lowest number of variants. Our analysis generated a priority list of genes, mutations and novel variants. This data will have an impact on informing decisions for screening and prevention programs and in management of vulnerable patients admitted to emergency, surgery, or interventions with bleeding side effects.