Qatar now has its own population-specific genome resource after researchers at Weill Cornell Medicine in New York and Qatar mapped the genomes of more than 1,000 Qatari nationals. This resource gives scientists a powerful reference tool that will facilitate efforts to identify genetic variations that cause serious and distressing conditions such as cystic fibrosis, sickle cell anemia and muscular dystrophy among the local population.
"This study is the first step in the development of precision medicine in Qatar," said co-senior author Dr. Ronald Crystal, chairman of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at Weill Cornell Medicine in New York. "Our genes decide how we respond to our environment and our risk for disease, and the variations in our genes are different for each population. With this initial description of the Qatari genome as a basis, and with future refinements to be made by the Qatari Genome Project, we now have the basis for defining the genetic risk of the Qatari population for disease, and how Qataris will respond to medical therapies."The new resource, published June 30 in Human Genome Variation, will also help doctors treating Qatari nationals to more effectively practice precision medicine, which involves analyzing a patient's genome in order to more effectively predict, diagnose and treat disease. A better understanding of the subtle variations in Qatari genomes will help researchers discover how certain ancestral genetic traits interact with environmental factors such as poor diet, lack of exercise and smoking to cause disease.
The project's completion is an important milestone in a new phase of genetic research, which has progressed from mapping the entire human genome — first achieved in 2003 after 13 years of investigation — to focusing on specific populations to identify correlations between shared heritage and susceptibility to particular diseases. This project is considered the most significant resource of genetic variants in any Arab population to date.
For the study, the research team — which comprised scientists from Weill Cornell Medicine-Qatar (WCM-Q), Weill Cornell Medicine, Sidra Medical and Research Center, Hamad Medical Corporation and Cornell University — gathered de-identified samples from more than 1,000 Qatari nationals who received care at Hamad Medical Corporation clinics. The scientists then used the advanced computing technology in the lab of the WCM-Q Genomics Core to analyze and map the genomes of each patient.
The scientists had previously identified three broad genomic groups within the Qatari population. The first group encompasses Bedouins, the second is a Persian or South Asian mixture, and the third comprises Qataris with sub-Saharan African heritage. In the latest study, supported by Qatar Foundation and Qatar National Research Fund, scientists achieved a higher resolution of ancestry. For example, individuals of Persian ancestry can now be distinguished from individuals of South Asian ancestry. This genetic diversity is important to recognize and understand as each group is likely to be susceptible to different conditions and react to environmental hazards in different ways, the investigators said.
Until now, researchers have usually attempted to identify disease-causing genetic variations by using powerful computers to compare the genomes of affected people with a global genome resource and searching for telltale differences between the two. Unfortunately, comparing the genomes of Qatari nationals with the global genome is problematic because the computer identifies tiny variations that may appear rare relative to the global genome average but are in fact very common among individuals of similar ancestries to the affected patient.
"One of the reasons genetics is complicated is that, in the genomes of every population we look at, we find millions of mutations, yet most of these do not actually cause disease - they appear to be harmless," said lead author Dr. Khalid Fakhro, an investigator at Sidra Medical and Research Center and an assistant professor in the Department of Genetic Medicine at WCM-Q. "So when a person with disease shows up in the clinic, it is more difficult than people imagine to identify the few potentially harmful mutations in a sea of mostly harmless variation."
The new population-specific resource mitigates this problem for Qatari nationals by providing a Qatari-specific genome resource, compiled from more than 1,000 Qataris whose families have enjoyed good health for at least three generations.
"Because many of the same harmless mutations are shared by members of the same population, using a population-specific resource makes it easier to identify abnormal mutations in the genome that do cause disease," Dr. Fakhro said. "Specifically, if we find a mutation shared by patients but it has never been observed in more than 1,000 ethnically-matched controls, we have higher confidence in its possible pathogenicity."
Given the shared heritage of Qatar's population with people in other parts of the Middle East and North Africa, the new Qatar Genome reference could also benefit patients across the region.
"This research has proven to be extremely exciting and worthwhile, not only for the new discoveries we have made but because there is great potential for clinical applications that will benefit patients in Qatar and the wider region," Dr. Crystal said. "We are very grateful for the support provided by Qatar National Research Fund and Qatar Foundation, without which this research could not have been undertaken."