May 21, 2024

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Largest ever Arab genome study opens door to precision medicine

5 min read

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A large-scale analysis provides new insights into Arab populations’ genetic heritage. Jasmin Merdan/Getty Images

The Middle East is geographically at the crossroads of human migration and culture. Despite this, the genetic heritage of Arab populations has historically been understudied. New research identifies complex distinctions in genomes that help map the origins and migrations of Arabic people.

Scientists affiliated with Sidra Medicine’s Department of Human Genetics in Doha, Qatar, collaborated with an international team of researchers to perform the largest study to date of Arabic genomics.

The researchers analyzed the genomes of 6,218 people from the Qatar Biobank.

Based on this work, which appears in Nature Communications, the Qatari researchers have concluded that modern Arabic populations share their genetic heritage with the most ancient humans in history. Additionally, they have revealed that Arabic people possess extensive genetic diversity.

Principal investigator Dr. Younes Mokrab — Assistant Professor at Weil Cornel Medicine in Qatar and Head of Medical and Population Genomics Laboratory at Sidra Medicine — explained to Medical News Today:

“In general, because of the lack of sufficient genetic data on Arabs within the landscape of human ancestry, it has been long assumed that Arabs were descendants of Europeans, or very closely related.”

“Our study provides the first substantial genetic evidence that this is not the case. Genetically, Arab lineages are very much distinct from Europeans. We discovered that the ancestors of modern Arabs are much more ancient than the ancestors of modern South Asians or Europeans. Basically, Arab populations are much older.”

“Also, for a very long time, Arabs have been considered to form one more-or-less homogenous population. However, by looking at even the relatively small population of Qatar, we found multiple diverse distinct genetic groups, which reflect the wider Arab and Middle Eastern region.

In their paper, the study authors note that Arabic populations divide into Qahtanite (Peninsular Arabs) and Adnanite Arabs (General Arabs and West Eurasian Arabs).

As a result of their genomic work, the scientists have concluded that Peninsular Arabs are the closest relatives of ancient hunter-gatherers and Neolithic farmers from the Levant — an area encompassing the eastern Mediterranean, including North Africa.

Using “genetic footprints” — tracing genetic mutations through individuals and populations — the researchers identified three significant periods of Arabic migration: 70,000 years ago, 32,000–42,000 years ago, and then 12,000–20,000 years ago.

At that 20,000-year inflection point, the scientists identified an ancestral Arab population that dominated the Levant region: the Peninsular Arabs.

After comparing reservoirs of ancient DNA with the people in the Qatar Genome Programme (QGP), the researchers concluded that these groups are linked.

When MNT asked Dr. Mokrab how researchers identified these periods of Arabic migration, he explained:

“Modern humans have essentially descended form a small group of founder individuals. Our genetic makeup provides footprints on how we diverged from each other.”

“In population genetics, we look at genetic mutations in a large number of genomes to establish how populations are related and trace back when they started diverging from each other. In this study we used state of the art statistical methods to measure those relationships and date the splitting events that happened in the past which shaped modern Arab populations.”

“What is unique in our study is that we looked at more than 6,000 Qatari genomes, the first time this has ever been done at this scale. As well as establishing ancient events in this population, we also compared the data to that of modern populations from various continents.”

“There, we found evidence of more recent Arab genetic flow to Europe, Africa, South Asia, and reaching as far as South America. This itself fits perfectly what we know about Islamic expansion out of Arabia which started 14 centuries years ago.”

In the Arabic people whom they studied, the researchers discovered as much as 20–50% genetic kinship, or consanguinity, among individuals.

This relatedness is far higher in Arabic people than in other ethnic groups. Such close family ties mean that people have a higher chance of inheriting genetic diseases.

Before this study, limited genomic data existed for Arabic populations. This new reservoir of data identifies genetic risks for Arabic descendants and could broadly improve medical care for all societies.

Dr. Mokrab observed:

“The high level of consanguinity within Arab populations means the likelihood of recessive genetic diseases is higher than in other parts of the world. As such, we are much more likely to discover rare forms of diseases, which by studying would lead us to better understanding of common diseases affecting broader populations worldwide. This is a real challenge and, at the same time, a tremendous opportunity for discovery.”

Genomic studies are the first step in precision medicine, which refers to tailoring medical research and therapy to the individual.

The Qatari scientists and their international collaborators leveraged this massive volume of data to create a genome panel for Arabic people.

The researchers used their genomic analysis to identify 12,432 haplotypes. Haplotypes are gene sequences that consistently occur together, usually emanating from one parent.

Geneticists worldwide are rapidly associating gene mutations with biological traits and diseases using genome-wide association studies. For Arabic people, the first-of-its-kind QGP “reference library” of haplotypes may help individuals identify and modify their risk of developing diseases.

Regarding this genomic reference dataset, Dr. Mokrab told MNT:

“We know that our genomes are constructed in terms of building blocks. So, there are essentially markers within the genomes. If you have marker X, Y, or Z, that means your gene [always] looks like ‘this.’ So, you don’t have to actually go there and sequence that part of the genome to be able to know that!”

“The idea is that by using sequences of well-defined genomes for a given population, if you want to sequence the next few thousand persons — you won’t necessarily need to go and physically sequence all of their genomes from scratch, you can just copy that.”

“This has a tremendous impact on how fast we can scale up things and the saving we can make on that. Having such a panel for Arab and Middle Eastern populations, it is a game changer for many countries in the region.”

Finally, Dr. Mokrab sees his teams’ addition of Arab genomic data — the QGP reference data set of haplotypes — as leveling the genomic playing field for all people with Arab and Middle Eastern descent. With this data, nations from the region can study genomes and help their citizens with much less expense.

As precision medicine advances, these researchers from Qatar have given clinicians and patients a “head start” to diagnose and target disease at the level of the gene.

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