HLA Diversity in Saudi Population: High Frequency of Homozygous HLA Alleles and Haplotypes

Chentoufi, Aziz Alami; Uyar, Fatma; Chentoufi, Hiba A.; Alzahrani, Khalid Ahmed; Paz, Maria R.; Bahnassy, Ahmed A; Elyamany, Ghaleb; Elghazaly, Assem

doi:10.3389/fgene.2022.898235

Cited by 5 publications

(4 citation statements)

References 48 publications

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“…In addition, streamlining the process of generating clinical-grade iPSCs will facilitate the establishment and future expansion of the bank to include additional haplotypes. Moreover, due to high level of consanguinity in the Saudi population, there is a considerable excess homozygosity, which may facilitate the identification of homozygous donors and haplobanking (Chentoufi et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

HLA-Based Banking of Human Induced Pluripotent Stem Cells in Saudi Arabia

Alowaysi,

Lehmann,

Al-Shehri

et al. 2023

Preprint

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Human iPSCs' derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time for autologous iPS-based cellular therapy, and the genetic engineering of hypo-immunogenic iPS cell lines is hampered with numerous hurdles. Therefore, it is increasingly interesting to create cell stocks based on HLA haplotype distribution in a given population. In this study, we assessed the potential of HLA-based iPS banking for the Saudi population. First, we analyzed the HLA database of the Saudi Stem Cell Donor Registry (SSCDR), which contains high-resolution HLA genotype data of 64,315 registered Saudi donors at the time of analysis. We found that only 13 iPS lines would be required to cover 30% of the Saudi population, 39 iPS lines would offer 50% coverage and 596 for more than 90% coverage. Next, As a proof-of-concept, we launched the first HLA-based banking of iPSCs in Saudi Arabia. Using clinically relevant methods, we generated the first iPSC line from a homozygous donor for the most common HLA haplotype in Saudi. The two generated clones expressed pluripotency markers, could be differentiated into all three germ layers, beating cardiomyocytes and neuronal progenitors. To ensure that our reprogramming method generates genetically stable iPSCs, we assessed the mutational burden in the generated clones and the original blood sample from which the iPSCs were derived using whole-genome sequencing. All detected variants were found in the original donor sample and were classified as benign according to current guidelines of the American College of Medical Genetics and Genomics (ACMG). This study sets a road map for introducing iPS-based cell therapy in the Kingdom of Saudi Arabia.

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Section: Discussionmentioning

confidence: 99%

HLA-Based Banking of Human Induced Pluripotent Stem Cells in Saudi Arabia

Alowaysi,

Lehmann,

Al-Shehri

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, streamlining the process of generating clinical-grade iPSCs will facilitate the establishment and future expansion of the bank to include additional haplotypes. Moreover, due to high level of consanguinity in the Saudi population, there is a considerable excess homozygosity, which may facilitate the identi cation of homozygous donors and haplobanking (Chentou et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

HLA-Based Banking of Induced Pluripotent Stem Cells in Saudi Arabia

Alowaysi,

Lehmann,

Al-Shehri

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Human iPSCs' derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time for autologous iPS-based cellular therapy, and the genetic engineering of hypo-immunogenic iPS cell lines is hampered with numerous hurdles. Therefore, it is increasingly interesting to create cell stocks based on HLA haplotype distribution in a given population. This study aimed to assess the potential of HLA-based iPS banking for the Saudi population.Methods: In this study, we interrogated HLA database of the Saudi Stem Cell Donor Registry (SSCDR), containing high-resolution HLA genotype data from 64,315 registered Saudi donors at the time of analysis. This database was considered to be a representative sample of the Saudi population. The most frequent HLA haplotypes in the Saudi population were determined and an in-house developed iterative algorithm was used to identify their HLA matching percentages in the SSCDR database and cumulative coverage. Subsequently, to develop a clinically-relevant protocol for iPSCs generation, and to illustrate the applicability of the concept of HLA-based banking for cell therapy purposes, the first HLA-based iPS cell line in Saudi Arabia was generated. Clinically relevant methods were employed to generate the 2 iPS clones from a homozygous donor for the most prevalent HLA haplotype in the Saudi population. The generated lines were then assessed for pluripotency markers, and their ability to differentiate into all three germ layers, beating cardiomyocytes and neural progenitors was examined. Additionally, the genetic stability of the HLA-iPS cell lines was verified by comparing the mutational burden in the clones and the original blood sample, using whole-genome sequencing. The standards set by the American College of Medical Genetics and Genomics (ACMG) were used to determine the clinical significance of identified variants.Results: The analysis revealed that the establishment of only 13 iPSC lines would match 30% of the Saudi population, 39 lines would attain 50% coverage, and 596 lines would be necessary for over 90% coverage. The proof-of-concept HLA-iPSCs, which cover 6.1% of the Saudi population, successfully demonstrated pluripotency and the ability to differentiate into various cell types including beating cardiomyocytes and neuronal progenitors. The comprehensive genetic analysis corroborated that all identified variants in the derived iPSCs were inherently present in the original donor sample and were classified as benign according to the standards set by the ACMG.Conclusions: Our study sets a road map for introducing iPS-based cell therapy in the Kingdom of Saudi Arabia. It underscores the pragmatic approach of HLA-based iPSC banking which circumvents the limitations of autologous iPS therapies. The successful generation and validation of iPSC lines based on prevalent HLA haplotypes signify a promising step towards broadening the accessibility and applicability of stem cell therapies and regenerative medicine in Saudi Arabia.

show abstract

Section: Discussionmentioning

confidence: 99%

HLA-based banking of induced pluripotent stem cells in Saudi Arabia

Alowaysi,

Lehmann,

Al-Shehri

et al. 2023

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Human iPSCs' derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time associated with autologous iPS-based cellular therapy, and the genetic engineering of hypo-immunogenic iPS cell lines is hampered with numerous hurdles. Therefore, it is increasingly interesting to create cell stocks based on HLA haplotype distribution in a given population. This study aimed to assess the potential of HLA-based iPS banking for the Saudi population. Methods In this study, we interrogated the HLA database of the Saudi Stem Cell Donor Registry (SSCDR), containing high-resolution HLA genotype data from 64,315 registered Saudi donors at the time of analysis. This database was considered to be a representative sample of the Saudi population. The most frequent HLA haplotypes in the Saudi population were determined, and an in-house developed iterative algorithm was used to identify their HLA matching percentages in the SSCDR database and cumulative coverage. Subsequently, to develop a clinically relevant protocol for iPSCs generation, and to illustrate the applicability of the concept of HLA-based banking for cell therapy purposes, the first HLA-based iPS cell line in Saudi Arabia was generated. Clinically relevant methods were employed to generate the two iPS clones from a homozygous donor for the most prevalent HLA haplotype in the Saudi population. The generated lines were then assessed for pluripotency markers, and their ability to differentiate into all three germ layers, beating cardiomyocytes, and neural progenitors was examined. Additionally, the genetic stability of the HLA-iPS cell lines was verified by comparing the mutational burden in the clones and the original blood sample, using whole-genome sequencing. The standards set by the American College of Medical Genetics and Genomics (ACMG) were used to determine the clinical significance of identified variants. Results The analysis revealed that the establishment of only 13 iPSC lines would match 30% of the Saudi population, 39 lines would attain 50% coverage, and 596 lines would be necessary for over 90% coverage. The proof-of-concept HLA-iPSCs, which cover 6.1% of the Saudi population, successfully demonstrated pluripotency and the ability to differentiate into various cell types including beating cardiomyocytes and neuronal progenitors. The comprehensive genetic analysis corroborated that all identified variants in the derived iPSCs were inherently present in the original donor sample and were classified as benign according to the standards set by the ACMG. Conclusions Our study sets a road map for introducing iPS-based cell therapy in the Kingdom of Saudi Arabia. It underscores the pragmatic approach of HLA-based iPSC banking which circumvents the limitations of autologous iPS-based cellular therapies. The successful generation and validation of iPSC lines based on the most prevalent HLA haplotype in the Saudi population signify a promising step toward broadening the accessibility and applicability of stem cell therapies and regenerative medicine in Saudi Arabia.

show abstract

HLA Diversity in Saudi Population: High Frequency of Homozygous HLA Alleles and Haplotypes

Cited by 5 publications

References 48 publications

HLA-Based Banking of Human Induced Pluripotent Stem Cells in Saudi Arabia

HLA-Based Banking of Human Induced Pluripotent Stem Cells in Saudi Arabia

HLA-Based Banking of Induced Pluripotent Stem Cells in Saudi Arabia

HLA-based banking of induced pluripotent stem cells in Saudi Arabia

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