ARCHIVE. Genetic research has evolved from mapping the entire human genome to deciphering areas along it that relate to a specific disease. The next phase involves research localized to specific parts of the world in order to discover patterns in heritage and genetic susceptibilities to disease. A group of such projects based on the local Qatari population has so far yielded results that shine light on the specific ancestral background of the local population and also points to areas of the Qatari genome that could potentially allow prediction and intervention. These projects are led by Dr. Ronald Crystal, Chairman of Genetic Medicine at Weill Cornell Medical College.
“The basic goal involves trying to understand the structure of the genome of the Qataris and put that in context with the environment to see how we can use that information to help the population in terms of general health, understanding disease, developing appropriate therapies and so on,” he said.
Some of the first results Dr. Crystal’s team published resolved the broad genomic makeup of the Qatari population, which, as published, can be generally separated into three categories—referred to as Q1, Q2 and Q3. Q1 are largely Bedouins, Q2 are a Persian or South Asian mixture and Q3 are the African-derived Qataris. While these groups are not perfectly “pure” per se, they are distinct enough to categorize.
“This is very, very important,” Dr. Crystal said, “because from everything we are learning in genetics, the responses to the environment are different depending on your genetic makeup. The fact that we can break the Qatari population into three is a very important because we can now study the responses of the different genetic populations to the same environmental stress. It may be that the Q1, Q2, Q3 populations respond differently to that same stress.”
Stress can be anything from smoking shisha to living a sedentary lifestyle to eating an imbalanced diet. Another environmental factor that is often separated into a category of its own, however, is drug metabolism—the way the body responds to certain drugs. And this, Dr. Crystal explained, is often predicted by genetics.
“I’m allergic to sulfur drugs,” Dr. Crystal said. “So if I take a drug that has a sulfur compound in it, I’ll develop a rash. You take the same drug and you probably won’t. This is on a genetic basis. We don’t know all the genes that control that but undoubtedly it’s on a genetic basis. So we have the whole population exposed to them but only some people will have adverse reactions to certain drugs.”
As more studies into the local population take shape, researchers will also be able to isolate more monogenetic - single gene-caused - diseases. A well-known example in the Qatari population is thalassemia, a blood thinning disorder.
The researchers, based in Qatar and New York, have published preliminary work related to a detailed/complete investigation of seven Qatari genomes. What has been published so far took into account thousands of positions along the genome - known as exome regions - that relate directly to human health and reveal many clues about the variability of genetics across populations.
A larger study, expanding on the publication, is well underway and involves the exome analysis, also known as “sequencing,” of 1,000 Qataris. The team has completed 600 of the samples, and Dr. Crystal said the remainder will be complete within the coming year.
Color coded areas note where areas of sampled Qatari genomes most closely match regions of the world in terms of ancestry. (plot from: Exome Sequencing of Only Seven Qataris Identifies Potentially Deleterious Variants in the Qatari Population. PLoS One. 7:11; 2012)
“One thousand people is 0.3 percent of the whole Qatari population,” he said, emphasizing this as a healthy start to discovering strong relationships between genetic markers and disease. “Our goal over the long run is to help develop a chip that can be used by the lab to screen married couples and also newborns, so that’s a real example of how genetics can be useful for a population … how understanding and having a strategy around genetic variability can be a real positive outcome for public health.
“As you know, the Qataris, like some other populations in the Middle East, have increased susceptibility to some diseases: diabetes, cardiovascular disease, obesity, some neurological disorders, and so on. And so if we can understand the differences between the Qatari populations and other world populations, we can begin to understand and contribute to understanding why the Qataris are more susceptible to certain disorders.”
In terms of privacy and social implications, Dr. Crystal explained that every detail has been considered. The samples were taken with permission and measures were taken to code samples with numbers to ensure results could not be traced to individuals. The complications arise, however, when people must decide if they want to know the results.
“There’s also another important issue called genomic anxiety, he said. “In other words, if I told you that you have a risk for diabetes or cardiovascular disease, you can say that’s something you might want to know because you could monitor your blood sugars and exercise and watch your diet and so on. But what if I told you that you have a high risk for early onset Alzheimer’s disease?”
Therapy currently does not exist around Alzheimer’s, but researchers can pinpoint a 20-fold increase in risk around the disease based on genetic analysis, Dr. Crystal said. In fact it caused him to pause for thought about getting his own genome sequenced. Yet the potential benefits of knowing the altered points in a genome speak for themselves.
“There’s a good example in some blood thinning drugs,” he said, “where there are clearly genetic factors that control their metabolism and whether a patient will have susceptibility to bleeding, and it can be life threatening, and we are very cognizant of that and we are dealing with that in the US, and there’s a lot of discussion around this and I think the same will be true in Qatar.”
Dr. Crystal’s team is extremely grateful for support from QNRF, which is allowing them to participate in the leading edge of genetics research.
“We have a grant to study the structure of the genome; we have a grant to study complications like retinopathy and diabetes; we have a grant together with the lab people at Hamad Medical Corporation to study the genetic variants associated with genetic disorders … so we have several grants being supported. I mean we couldn’t do this without the support of the Qatar Foundation and QNRF.
“I think that Qataris are very smart in that they're investing significantly not only in education but also in biomedical research that will directly help the population, and I hope this is a good example of that,” he continued. “Our goal is to try to develop genetic information that will be directly helpful in terms of medical care.”
Whole genome sequencing of the Qatari population