Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population
Abstract Background Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is the most common red cell enzymopathy in the world. In Qatar, the incidence of G6PDD is estimated at around 5%; however, no study has investigated the genetic basis of G6PDD in the Qatari population yet. Methods In this study...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-021-00358-9 |
| _version_ | 1811279564720046080 |
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| author | Shaza Malik Roan Zaied Najeeb Syed Puthen Jithesh Mashael Al-Shafai |
| author_facet | Shaza Malik Roan Zaied Najeeb Syed Puthen Jithesh Mashael Al-Shafai |
| author_sort | Shaza Malik |
| collection | DOAJ |
| description | Abstract Background Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is the most common red cell enzymopathy in the world. In Qatar, the incidence of G6PDD is estimated at around 5%; however, no study has investigated the genetic basis of G6PDD in the Qatari population yet. Methods In this study, we analyzed whole-genome sequencing data generated by the Qatar Genome Programme for 6045 Qatar Biobank participants, to identify G6PDD variants in the Qatari population. In addition, we assessed the impact of the novel variants identified on protein function both in silico and by measuring G6PD enzymatic activity in the subjects carrying them. Results We identified 375 variants in/near G6PD gene, of which 20 were high-impact and 16 were moderate-impact variants. Of these, 14 were known G6PDD-causing variants. The most frequent G6PD-causing variants found in the Qatari population were p.Ser188Phe (G6PD Mediterranean), p.Asn126Asp (G6PD A +), p.Val68Met (G6PD Asahi), p.Ala335Thr (G6PD Chatham), and p.Ile48Thr (G6PD Aures) with allele frequencies of 0.0563, 0.0194, 0.00785, 0.0050, and 0.00380, respectively. Furthermore, we have identified seven novel G6PD variants, all of which were confirmed as G6PD-causing variants and classified as class III variants based on the World Health Organization’s classification scheme. Conclusions This is the first study investigating the molecular basis of G6PDD in Qatar, and it provides novel insights about G6PDD pathogenesis and highlights the importance of studying such understudied population. |
| first_indexed | 2024-04-13T00:56:44Z |
| format | Article |
| id | doaj.art-bbf18ef9e3564573a9cd99ae92d2f579 |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-13T00:56:44Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-bbf18ef9e3564573a9cd99ae92d2f5792022-12-22T03:09:38ZengBMCHuman Genomics1479-73642021-10-0115111010.1186/s40246-021-00358-9Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari populationShaza Malik0Roan Zaied1Najeeb Syed2Puthen Jithesh3Mashael Al-Shafai4Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar UniversityDepartment of Biomedical Sciences, College of Health Sciences, QU Health, Qatar UniversityApplied Bioinformatics Core, Sidra MedicineApplied Bioinformatics Core, Sidra MedicineDepartment of Biomedical Sciences, College of Health Sciences, QU Health, Qatar UniversityAbstract Background Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is the most common red cell enzymopathy in the world. In Qatar, the incidence of G6PDD is estimated at around 5%; however, no study has investigated the genetic basis of G6PDD in the Qatari population yet. Methods In this study, we analyzed whole-genome sequencing data generated by the Qatar Genome Programme for 6045 Qatar Biobank participants, to identify G6PDD variants in the Qatari population. In addition, we assessed the impact of the novel variants identified on protein function both in silico and by measuring G6PD enzymatic activity in the subjects carrying them. Results We identified 375 variants in/near G6PD gene, of which 20 were high-impact and 16 were moderate-impact variants. Of these, 14 were known G6PDD-causing variants. The most frequent G6PD-causing variants found in the Qatari population were p.Ser188Phe (G6PD Mediterranean), p.Asn126Asp (G6PD A +), p.Val68Met (G6PD Asahi), p.Ala335Thr (G6PD Chatham), and p.Ile48Thr (G6PD Aures) with allele frequencies of 0.0563, 0.0194, 0.00785, 0.0050, and 0.00380, respectively. Furthermore, we have identified seven novel G6PD variants, all of which were confirmed as G6PD-causing variants and classified as class III variants based on the World Health Organization’s classification scheme. Conclusions This is the first study investigating the molecular basis of G6PDD in Qatar, and it provides novel insights about G6PDD pathogenesis and highlights the importance of studying such understudied population.https://doi.org/10.1186/s40246-021-00358-9G6PD deficiencyWhole-genome sequencing (WGS)Novel variantsQatar Biobank (QBB)Qatar Genome Programme (QGP) |
| spellingShingle | Shaza Malik Roan Zaied Najeeb Syed Puthen Jithesh Mashael Al-Shafai Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population Human Genomics G6PD deficiency Whole-genome sequencing (WGS) Novel variants Qatar Biobank (QBB) Qatar Genome Programme (QGP) |
| title | Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population |
| title_full | Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population |
| title_fullStr | Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population |
| title_full_unstemmed | Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population |
| title_short | Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population |
| title_sort | seven novel glucose 6 phosphate dehydrogenase g6pd deficiency variants identified in the qatari population |
| topic | G6PD deficiency Whole-genome sequencing (WGS) Novel variants Qatar Biobank (QBB) Qatar Genome Programme (QGP) |
| url | https://doi.org/10.1186/s40246-021-00358-9 |
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