DALIA- a comprehensive resource of Disease Alleles in Arab population

Vatsyayan, Aastha; Sharma, Parul; Gupta, Shrey; Sandhu, Sumiti; Venu, Seetha Lakshmi; Sharma, Vandana; Badaoui, Bouabid; Azedine, Kaidi; Youssef, Serti; Rajab, Anna; Fayez, Alaaeldin; Madinur, Seema; Ranawat, Anop Singh; Pandhare, Kavita; Ramachandran, Srinivasan; Sivasubbu, Sridhar; Scaria, Vinod

doi:10.1371/journal.pone.0244567

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…The absence of a variant in publicly available population databases is thus currently of limited value for indicating pathogenicity in ethnically diverse populations, underscoring the importance of continued efforts to diversify the genomic evidence base (Koch, 2020). While several population‐specific databases including GenomeAsia (https://browser.genomeasia100k.org/) (Wall et al, 2019) and the Greater Middle East (GME) Variome Project (http://igm.ucsd.edu/gme/) (Scott et al, 2016; Vatsyayan et al, 2021) are ongoing to specifically address this genomic data disparity, all have no or very limited numbers of Palestinian exomes and genomes. This issue is further compounded by the relatively high number of homozygous missense variants typically identified in such genetically isolated communities, in which inter‐community marriage patterns tend to be common (Darr et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

TECPR2‐related hereditary sensory and autonomic neuropathy in two siblings from Palestine

Khalaf‐Nazzal,

Dweikat,

Ubeyratna

et al. 2024

American J of Med Genetics Pt A

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Due to the majority of currently available genome data deriving from individuals of European ancestry, the clinical interpretation of genomic variants in individuals from diverse ethnic backgrounds remains a major diagnostic challenge. Here, we investigated the genetic cause of a complex neurodevelopmental phenotype in two Palestinian siblings. Whole exome sequencing identified a homozygous missense TECPR2 variant (Chr14(GRCh38):g.102425085G>A; NM_014844.5:c.745G>A, p.(Gly249Arg)) absent in gnomAD, segregating appropriately with the inheritance pattern in the family. Variant assessment with in silico pathogenicity prediction and protein modeling tools alongside population database frequencies led to classification as a variant of uncertain significance. As pathogenic TECPR2 variants are associated with hereditary sensory and autonomic neuropathy with intellectual disability, we reviewed previously published candidate TECPR2 missense variants to clarify clinical outcomes and variant classification using current approved guidelines, classifying a number of published variants as of uncertain significance. This work highlights genomic healthcare inequalities and the challenges in interpreting rare genetic variants in populations underrepresented in genomic databases. It also improves understanding of the clinical and genetic spectrum of TECPR2‐related neuropathy and contributes to addressing genomic data disparity and inequalities of the genomic architecture in Palestinian populations.

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Section: Discussionmentioning

confidence: 99%

TECPR2‐related hereditary sensory and autonomic neuropathy in two siblings from Palestine

Khalaf‐Nazzal,

Dweikat,

Ubeyratna

et al. 2024

American J of Med Genetics Pt A

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“…There is thus a pressing need for better access and more comprehensive coverage of genetic data on Arabs. Although there have been attempts to fill this gap by other databases ( Scott et al, 2016 ; Koshy et al, 2017 ; Karczewski et al, 2020 ; Vatsyayan et al, 2021 ), to the best of our knowledge, CTGA is the most comprehensive compendium of bibliographic genetic data on Arab populations.…”

Section: Introductionmentioning

confidence: 99%

Spectrum of genetic disorders and gene variants in the United Arab Emirates national population: insights from the CTGA database

et al. 2023

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Like many other Arab countries, the United Arab Emirates (UAE) has a relatively high prevalence of genetic disorders. Here we present the first review and analysis of all genetic disorders and gene variants reported in Emirati nationals and hosted on the Catalogue for Transmission Genetics in Arabs (CTGA), an open-access database hosting bibliographic data on human gene variants associated with inherited or heritable phenotypes in Arabs. To date, CTGA hosts 665 distinct genetic conditions that have been described in Emiratis, 621 of which follow a clear Mendelian inheritance. Strikingly, over half of these are extremely rare according to global prevalence rates, predominantly with an autosomal recessive mode of inheritance. This is likely due to the relatively high consanguinity rates within the Emirati population. The 665 conditions include disorders that are unique to the Emirati population, as well as clearly monogenic disorders that have not yet been mapped to a causal genetic locus. We also describe 1,365 gene variants reported in Emiratis, most of which are substitutions and over half are classified as likely pathogenic or pathogenic. Of these, 235 had not been reported on the international databases dbSNP and Clinvar, as of December 2022. Further analysis of this Emirati variant dataset allows a comparison of clinical significance as reported by Clinvar and CTGA, where the latter is derived from the study cited. A total of 307 pathogenic/likely pathogenic variants from CTGA’s Emirati dataset, were classified as benign, variants of uncertain significance, or were missing a clinical significance or had not been reported by Clinvar. In conclusion, we present here the spectrum of genetic disorders and gene variants reported in Emiratis. This review emphasizes the importance of ethnic databases such as CTGA in addressing the underrepresentation of Arab variant data in international databases and documenting population-specific discrepancies in variant interpretation, reiterating the value of such repositories for clinicians and researchers, especially when dealing with rare disorders.

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Spectrum of Genetic Disorders and Gene Variants in the United Arab Emirates National Population: Insights from the CTGA Database

Bizzari

Nair

Hana

et al. 2023

Preprint

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Like many other Arab countries, the United Arab Emirates (UAE) has a relatively high prevalence of genetic disorders. Here we present the first review and analysis of all genetic disorders and gene variants reported in Emirati nationals and hosted on the Catalogue for Transmission Genetics in Arabs (CTGA), an open-access database hosting bibliographic data on human gene variants associated with inherited or heritable phenotypes in Arabs. To date, CTGA hosts 665 distinct genetic conditions that have been described in Emiratis, 621 of which follow a clear Mendelian inheritance. Strikingly, over half of these are extremely rare according to global prevalence rates, predominantly with an autosomal recessive mode of inheritance. This is likely due to the relatively high consanguinity rates within the Emirati population. The 665 conditions include disorders that are unique to the Emirati population, as well as clearly monogenic disorders that have not yet been mapped to a causal genetic locus. We also describe 1,365 gene variants reported in Emiratis, most of which are substitutions and over half are classified as likely pathogenic or pathogenic. Of these, 235 had not been reported on the international databases dbSNP and Clinvar, as of December 2022. Further analysis of this Emirati variant dataset allows a comparison of clinical significance as reported by Clinvar and CTGA, where the latter is derived from the study cited. A total of 306 pathogenic/likely pathogenic variants from CTGA's Emirati dataset, were classified as benign, variants of uncertain significance, or were missing a clinical significance or had not been reported by Clinvar. In conclusion, we present here the spectrum of genetic disorders and gene variants reported in Emiratis. This review emphasizes the importance of ethnic databases such as CTGA in addressing the underrepresentation of Arab variant data in international databases and documenting population-specific discrepancies in variant interpretation, reiterating the value of such repositories for clinicians and researchers, especially when dealing with rare disorders.

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DALIA- a comprehensive resource of Disease Alleles in Arab population

Cited by 4 publications

References 34 publications

TECPR2‐related hereditary sensory and autonomic neuropathy in two siblings from Palestine

TECPR2‐related hereditary sensory and autonomic neuropathy in two siblings from Palestine

Spectrum of genetic disorders and gene variants in the United Arab Emirates national population: insights from the CTGA database

Spectrum of Genetic Disorders and Gene Variants in the United Arab Emirates National Population: Insights from the CTGA Database

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