title: Clinical genomics can facilitate countrywide estimation of autosomal recessive disease burden.
abstract: Most autosomal recessive diseases are rare, but they collectively account for a substantial proportion of disease burden, especially in consanguineous populations. Estimation of this disease burden, however, is hampered by many factors, including lack of countrywide registries. Establishing carrier frequency can be a practical surrogate to estimate disease burden, although the requirement of a large representative cohort may be challenging.
  
  
  
  We propose that the application of clinical genomics in the diagnostic setting offers a unique opportunity to estimate carrier frequency in the population as a secondary benefit.
  
  
  
  We used a data set of ~7,100 patients who underwent genomic testing for various Mendelian disorders to estimate the carrier frequency.
  
  
  
  We were able to calculate the frequency of 259 confirmed founder recessive mutations. We found the corresponding disease burden to be, at minimum, ~7 per 1,000 children born to first-cousin parents, with disorders related to intellectual disability and vision impairment being the most common.
  
  
  
  Our approach can be utilized to inform the design of new policies for the prevention of genetic disorders and highlights an important secondary benefit of clinical genomics.Genet Med 18 12, 1244-1249.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abouelhoda
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
authors.forename: Turki
authors.identifier: 0000-0001-7655-4198
authors.initials: T
authors.lastname: Sobahy
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
authors.forename: Mohamed
authors.identifier: 0000-0003-1797-3098
authors.initials: M
authors.lastname: El-Kalioby
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Nisha
authors.identifier: 0000-0003-0953-4562
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hanan
authors.identifier: 0000-0002-6199-3523
authors.initials: H
authors.lastname: Shamseldin
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
authors.forename: Dorota
authors.identifier: 0000-0001-5785-6799
authors.initials: D
authors.lastname: Monies
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
authors.forename: Nada
authors.identifier: 0000-0001-9076-0334
authors.initials: N
authors.lastname: Al-Tassan
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Khushnooda
authors.initials: K
authors.lastname: Ramzan
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Faiqa
authors.identifier: 0000-0002-2961-5733
authors.initials: F
authors.lastname: Imtiaz
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Ranad
authors.identifier: 0000-0002-2590-1759
authors.initials: R
authors.lastname: Shaheen
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Fowzan S
authors.identifier: 0000-0003-4158-341X
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D003241:Consanguinity; D030541:Databases, Genetic; D005808:Genes, Recessive; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology; D005820:Genetic Testing; D023281:Genomics; D006579:Heterozygote; D006801:Humans; D009154:Mutation