Your browser doesn't support javascript.
loading
Analysis of incidental findings in Qatar genome participants reveals novel functional variants in LMNA and DSP.
Elfatih, Amal; Da'as, Sahar I; Abdelrahman, Doua; Mbarek, Hamdi; Mohammed, Idris; Hasan, Waseem; Fakhro, Khalid A; Estivill, Xavier; Mifsud, Borbala.
Afiliación
  • Elfatih A; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
  • Da'as SI; Department of Human Genetics, Sidra Medicine, Doha, Qatar.
  • Abdelrahman D; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
  • Mbarek H; Department of Human Genetics, Sidra Medicine, Doha, Qatar.
  • Mohammed I; Department of Human Genetics, Sidra Medicine, Doha, Qatar.
  • Hasan W; Qatar Genome Programme, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.
  • Fakhro KA; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
  • Estivill X; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
  • Mifsud B; Department of Human Genetics, Sidra Medicine, Doha, Qatar.
Hum Mol Genet ; 31(16): 2796-2809, 2022 08 23.
Article en En | MEDLINE | ID: mdl-35348702
In order to report clinically actionable incidental findings in genetic testing, the American College of Medical Genetics and Genomics (ACMG) recommended the evaluation of variants in 59 genes associated with highly penetrant mutations. However, there is a lack of epidemiological data on medically actionable rare variants in these genes in Arab populations. We used whole genome sequencing data from 6045 participants from the Qatar Genome Programme and integrated it with phenotypic data collected by the Qatar Biobank. We identified novel putative pathogenic variants in the 59 ACMG genes by filtering previously unrecorded variants based on computational prediction of pathogenicity, variant rarity and segregation evidence. We assessed the phenotypic associations of candidate variants in genes linked to cardiovascular diseases. Finally, we used a zebrafish knockdown and synthetic human mRNA co-injection assay to functionally characterize two of these novel variants. We assessed the zebrafish cardiac function in terms of heart rate, rhythm and hemodynamics, as well as the heart structure. We identified 52 492 novel variants, which have not been reported in global and disease-specific databases. A total of 74 novel variants were selected with potentially pathogenic effect. We prioritized two novel cardiovascular variants, DSP c.1841A > G (p.Asp614Gly) and LMNA c.326 T > G (p.Val109Gly) for functional characterization. Our results showed that both variants resulted in abnormal zebrafish heart rate, rhythm and structure. This study highlights medically actionable variants that are specific to the Middle Eastern Qatari population.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lamina Tipo A / Hallazgos Incidentales / Desmoplaquinas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals / Humans País/Región como asunto: Asia Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Qatar Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lamina Tipo A / Hallazgos Incidentales / Desmoplaquinas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals / Humans País/Región como asunto: Asia Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Qatar Pais de publicación: Reino Unido