A team led by collaborating researchers from Weill Cornell Medicine-Qatar (WCM-Q), Qatar Foundation (QF) and Weill Cornell Medicine in New York (WCM NY) have assembled a large genomic database on the Qatari people, and have used it to develop an advanced but low-cost screening tool for genetic diseases.
The tool, QChip1, is a microarray capable of detecting, from a blood sample, more than 80,000 different DNA variations in genes linked to hereditary disorders. Costing less than $100 each, QChip1 microarrays will be used to evaluate the risks of such disorders among newborns, couples planning a family and hospital patients.
As the researchers demonstrated in their study, published in npj Genomic Medicine, a population-specific screening tool is necessary in Qatar because the Qatari population has a largely distinct set of genetic disorder risk variants, 85% of which are not seen in Western populations. Other institutions in the collaboration include Sidra Medicine and Hamad Medical Corporation.
In the study, the researchers assembled a large dataset, from their own and others’ sequencing of DNA from more than 8,000 Qataris, to construct the Qatari Genome Knowledgebase of known risk variants.
Out of the millions of recorded variants in the Knowledgebase, they selected 83,542 known or likely disease-causing variants, in a total of 3,438 genes, to generate the probes for QChip1. Chips such as these are called genotyping microarrays, and contain arrays of short DNA strands each of which will bind to and register the presence of a DNA sequence of interest.
The researchers demonstrated QChip1 screening by using the chip to analyse DNA from 2,707 Qataris. In this large sample of individuals, they identified a total of 32,674 distinct risk variants, with an average of 134 risk variants per individual. They also found that these variants were relatively Qatari-specific, only about 15% of the variants being present in comparative DNA samples from European Americans, South Asian Americans, African Americans and Puerto Ricans.
“The genomic database of the Qatari population and the QChip technology provide an extremely accessible, low-cost and powerful resource for reducing the incidence of a wide variety of inherited diseases,” said co-first author Dr Amal Robay, assistant professor of research in genetic medicine at WCM-Q.
“Every day we discover more pathogenic variants, which are observed in some countries to be different from the variant observed in other countries,” said co-senior author Dr Asmaa al-Thani, chair of Qatar Genome Programme at QF and vice chair of Qatar Biobank Board. “Differences between pathogenic variants in different countries are reported on a daily basis, which keeps driving us to pursue our work in genomics, and focusing on pathogenic evolution and potentially pathogenic variants. With every new variant we observe as unique to Qatar, we take on step forward towards better health care, not only for Qatar, but also for other Middle Eastern populations.”
“The QChip1 screening array marks several key milestones for Qatar,” said study co-author Dr Khalid Fakhro, chief of research at Sidra Medicine. “First, it represents a significant outcome of Qatar’s early investment in generating genomic knowledge on our population. Second, this array is a first for the region, and can be adopted by neighbouring countries whose populations share ancestry (and disease mutations) with ours. And finally, it demonstrates the strength of collaboration across the biomedical research community in Qatar.”
“The important message here is that advancing precision medicine with genetic screening tools for a given population requires an understanding of the specific set of risk variants found in that population,” said study co-senior author Dr Ronald Crystal, chairman of the Department of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at WCM NY.
“The co-operation between multiple institutions is helping produce powerful screening tools, and the impact is not only reflected in the power of numbers, but also in the power of science,” said co-first author Dr Radja Messai-Badji, genomics operations manager at QF’s Qatar Genome Programme.
“This groundbreaking effort led by Weill Cornell Medicine highlights the effectiveness and translatability of omics and, in particular, genomic projects such as the QChip to implement precision medicine solutions that are likely to improve health care for the populations of Qatar and the wider region,” said study co-author Dr Khaled Machaca, senior associate dean for research, innovations and commercialisation and a professor of physiology and biophysics at WCM-Q.
Qatar is a good candidate for comprehensive and population-specific screening as traditional marriage practices often bring together two people who carry the same single-gene disorders (SGD).
“SGD risk screening has a lot of potential, not only clinically for personalised medicine and family planning, but also scientifically for understanding rare genetic diseases,” said co-first author Dr Juan Rodriguez-Flores, an assistant professor of research in genetic medicine at WCM NY.
As the researchers demonstrated in their study, published in npj Genomic Medicine, a population-specific screening tool is necessary in Qatar because the Qatari population has a largely distinct set of genetic disorder risk variants, 85% of which are not seen in Western populations. Other institutions in the collaboration include Sidra Medicine and Hamad Medical Corporation.
In the study, the researchers assembled a large dataset, from their own and others’ sequencing of DNA from more than 8,000 Qataris, to construct the Qatari Genome Knowledgebase of known risk variants.
Out of the millions of recorded variants in the Knowledgebase, they selected 83,542 known or likely disease-causing variants, in a total of 3,438 genes, to generate the probes for QChip1. Chips such as these are called genotyping microarrays, and contain arrays of short DNA strands each of which will bind to and register the presence of a DNA sequence of interest.
The researchers demonstrated QChip1 screening by using the chip to analyse DNA from 2,707 Qataris. In this large sample of individuals, they identified a total of 32,674 distinct risk variants, with an average of 134 risk variants per individual. They also found that these variants were relatively Qatari-specific, only about 15% of the variants being present in comparative DNA samples from European Americans, South Asian Americans, African Americans and Puerto Ricans.
“The genomic database of the Qatari population and the QChip technology provide an extremely accessible, low-cost and powerful resource for reducing the incidence of a wide variety of inherited diseases,” said co-first author Dr Amal Robay, assistant professor of research in genetic medicine at WCM-Q.
“Every day we discover more pathogenic variants, which are observed in some countries to be different from the variant observed in other countries,” said co-senior author Dr Asmaa al-Thani, chair of Qatar Genome Programme at QF and vice chair of Qatar Biobank Board. “Differences between pathogenic variants in different countries are reported on a daily basis, which keeps driving us to pursue our work in genomics, and focusing on pathogenic evolution and potentially pathogenic variants. With every new variant we observe as unique to Qatar, we take on step forward towards better health care, not only for Qatar, but also for other Middle Eastern populations.”
“The QChip1 screening array marks several key milestones for Qatar,” said study co-author Dr Khalid Fakhro, chief of research at Sidra Medicine. “First, it represents a significant outcome of Qatar’s early investment in generating genomic knowledge on our population. Second, this array is a first for the region, and can be adopted by neighbouring countries whose populations share ancestry (and disease mutations) with ours. And finally, it demonstrates the strength of collaboration across the biomedical research community in Qatar.”
“The important message here is that advancing precision medicine with genetic screening tools for a given population requires an understanding of the specific set of risk variants found in that population,” said study co-senior author Dr Ronald Crystal, chairman of the Department of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at WCM NY.
“The co-operation between multiple institutions is helping produce powerful screening tools, and the impact is not only reflected in the power of numbers, but also in the power of science,” said co-first author Dr Radja Messai-Badji, genomics operations manager at QF’s Qatar Genome Programme.
“This groundbreaking effort led by Weill Cornell Medicine highlights the effectiveness and translatability of omics and, in particular, genomic projects such as the QChip to implement precision medicine solutions that are likely to improve health care for the populations of Qatar and the wider region,” said study co-author Dr Khaled Machaca, senior associate dean for research, innovations and commercialisation and a professor of physiology and biophysics at WCM-Q.
Qatar is a good candidate for comprehensive and population-specific screening as traditional marriage practices often bring together two people who carry the same single-gene disorders (SGD).
“SGD risk screening has a lot of potential, not only clinically for personalised medicine and family planning, but also scientifically for understanding rare genetic diseases,” said co-first author Dr Juan Rodriguez-Flores, an assistant professor of research in genetic medicine at WCM NY.
