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Genomics-first approach helps disease diagnosis in Saudis

Published online 24 May 2019

The genetic sequences of thousands of Saudi families reveal novel disease-related genes, facilitating the diagnosis and prevention of rare genetic conditions.

Monica Hoyos Flight

Alkuraya and his colleagues say their analyses highlight the power of the genomics-first approach.
Alkuraya and his colleagues say their analyses highlight the power of the genomics-first approach.
Sateesh Maddirevula
Analyses of the genomes of more than 2,000 Saudi families have revealed over 270 new genes that could be involved in disease. Most of these genes are recessive, needing two copies of the gene, one from each parent, for a disease to emerge.

“Recessive causes accounted for at least 75 per cent of the developmental disorders in our Saudi patients, whereas a similar study in the UK identified a recessive cause in less than four per cent of patients,” says geneticist Fowzan Alkuraya of King Faisal Specialist Hospital and Research Centre, who led the study.

A new Ministry of Health decision means that any person in Saudi Arabia suspected of having a genetic disease can receive an all-expenses-paid analysis of the whole protein-coding part of their genome, called the exome. 

This has encouraged the kingdom’s clinicians to order clinical exome sequencing (CES) as a first-tier test for anyone with a suspected genetic diagnosis. It has also offered researchers the opportunity to look for recessive disease-causing genes. Consanguineous marriage between close relatives, like first cousins, is common in Saudi Arabia. This means recessive disease-causing genes can be more easily identified and studied compared to other populations.

Alkuraya and his colleagues analysed the results of 3,310 CES tests performed on 2,219 Saudi families.

The study identified 155 genes they believe to be associated with recessive diseases. They also found mutations in 64 previously reported disease candidate genes, providing further evidence of their involvement in disease. Another group of genes previously thought to only be involved in dominant diseases, where one disease-associated gene from one parent is needed for the condition to form, was found to have recessive forms that could also lead to disease.

Surprisingly, only a quarter of patients analysed had received an accurate clinical diagnosis prior to their CES results.

“This is a major reminder of why CES should be a first-tier test,” Alkuraya says. “It is unfair for patients to be at the mercy of their physician’s ability to recognize their genetic disorder clinically, which our data shows only happens successfully in a small minority.” 

“This thoughtfully designed and conducted study contributes to informing the growing clinical genomics knowledgebase and highlights the diagnostic utility of genetic information,” says biomedical data scientist Martha Ragan Hart of Stanford University, USA, who was not involved in the study.

Whole exome sequencing in consanguineous populations offers unique opportunities for disease prevention through public health education, pre-marital screening programs and genetic counselling to explore reproductive options. “We hope decision-makers in Saudi Arabia will be emboldened by these results and continue to support the implementation of genomic medicine,” Alkuraya says.


Monies, D. et al. Lessons learned from large-scale, first-tier clinical exome sequencing in a highly consanguineous population. Am. J. Hum. Genet. 104, 1–20 (2019).