Arab founder variants: Contributions to clinical genomics and precision medicine.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
AlAbdi Lama, Maddirevula Sateesh, Aljamal Bayan, Hamid Halima, Almulhim Aisha, Hashem Mais O, Algoos Yusra, Alqahtani Mashael, Albaloshi Shahad, Alghamdi Mohammed, Alduaylij Mohammed, Shamseldin Hanan E, Nadeef Seba, Patel Nisha, Abdulwahab Firdous, Abouyousef Omar, Alshidi Tarfa, Jaafar Amal, Abouelhoda Mohamed, Saudi Mendeliome Group, Alhazzani Adel, Alfares Ahmed, Qudair Ahmad, Alsulaiman Ahood, Alhashem Amal, Khan Arif O, Chedrawi Aziza, Alebdi Basel, AlAjlan Fahad, Alotaibi Fawaz, Alzaidan Hamad, Banjar Hanaa, Abdelraouf Hanem, Alkuraya Hisham, Abumansour Iman, Alfayez Khowlah, Tulbah Maha, Alowain Mohammed, Alqahtani Mohammed, El-Kalioby Mohammed, Shboul Mohammad, Sulaiman Raashda, Al Tala Saed, Khan Sameena, Coskun Serdar, Mrouge Sobaihi, Alenazi Walaa, Rahbeeni Zuhair, Alkuraya Fowzan S
Аннотация
METHODS: Using one of the largest datasets on Mendelian disorders in the Middle East, we identified 2,908 medically relevant founder variants derived from 18,360 exomes and genomes and investigated their contribution to the clinical annotation of the human genome.
FINDINGS: Strikingly, ∼34% of Arab founder variants are absent in gnomAD. We found a strong contribution of Arab founder variants to the identification of novel gene-disease links (n = 224) and the support/dispute (n = 81 support, n = 101 dispute) of previously reported candidate gene-disease links. The powerful segregation evidence generated by Arab founder variants allowed many ClinVar and Human Gene Mutation Database variants to be reclassified. Overall, 39.5% of diagnostic reports from our clinical lab are based on founder variants, and 19.41% of tested individuals carry at least one pathogenic founder variant. The presumptive loss-of-function mechanism that typically underlies autosomal recessive diseases means that Arab founder variants also offer unique opportunities in "druggable genome" research. Arab founder variants were also informative of migration patterns in the Middle East consistent with documented historical accounts.
CONCLUSIONS: We highlight the contribution of founder variants from an under-represented population group to precision medicine and inform future prevention programs. Our study also sheds light on the added value of these variants in supplementing other lines of research in tracing population history.
FUNDING: There is no funding for this work.