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Bridging the gap — study sequences Asian genomes to diversify genetic databases

The international effort focuses on the genomes of 100,000 Asian individuals to better understand genetic diseases

<p>The project hopes to provide new insights into inherited diseases as well as those caused by a combination of genetic and environmental factors.</p>

The project hopes to provide new insights into inherited diseases as well as those caused by a combination of genetic and environmental factors.

Though the number of human genomes sequenced continues to rise rapidly since the completion of the Human Genome Project — a scientific endeavor spanning multiple decades and countries aimed at detailing human DNA — in 2003, less than 10 percent of those genomes to date correspond to individuals of Asian descent. The GenomeAsia 100K Project, a non-profit consortium, seeks to change this lack of knowledge surrounding a major portion of the world’s ethnicities. The conglomeration of researchers and private sector executives from around the world — from Seoul, South Korea to the University — plans to add 100,000 novel genomes from individuals of Asian ethnicity to new open-access databases.

Academic institutions and private sector companies came together in 2016 to launch the GenomeAsia 100K Project. While the research organization MedGenome and Nanyang Technological University in Singapore originally founded the non-profit consortium, representatives from other businesses and schools including Genentech, Macrogen and the University of California, San Francisco have joined the association.

Since genome sequencing can reveal the unique characteristics of each person’s genetic material, it can help determine a person’s ancestry and the propensity for certain medical conditions. According to GenomeAsia 100K, Asians constitute nearly half of the world’s population, and the distinct ethnicities and communities offer a relatively untapped repository of genetic diversity. The project hopes to provide new insights into inherited diseases as well as those caused by a combination of genetic and environmental factors.

Aakrosh Ratan, assistant professor of public health sciences and researcher for GenomeAsia 100K, explained that in particular, the information the initiative collects may help develop medical treatments based on people’s specific genetic makeup, instead of relying on traditional general treatments that may not target the unique root cause of each patient’s form of a disease.

“The goal of precision medicine is to tailor treatment towards a person’s genetic background, and that dream cannot be realized until you have the proper reference databases,” Ratan said.

Mutations in humans’ DNA sequences lead to different copies of the same gene within a person and amongst ethnicities. These different versions of a gene can act as markers of diseases that are inherited or influenced by genetic makeup. For example, the disorder sickle cell anemia is caused by the change of a single point in the DNA sequence. When someone is born with copies of this particular gene from both parents contain the mutation, he or she will suffer from often debilitating pain resulting from red blood cells that cannot effectively transport oxygen.

Ratan explained that genome sequencing can highlight mutations in a person’s DNA that may cause illnesses such as sickle cell anemia.

“One of the ways we identify the mutations that drive a rare disease is by identifying the mutations … and then prioritizing those mutations based on their prevalence in healthy populations,” Ratan said. “With the medical datasets we have compiled, we can actually improve such analyses for patients of Asian descent.” 

As of December 2019, the GenomeAsia 100K Project has completed the analysis of 1,739 genomes from 219 populations and 64 countries worldwide. Preliminary findings appeared that same month in the scientific journal Nature. The paper concluded that the sample provided a reasonable framework for sequencing practices and studying the history and health of Asian populations. Ratan and his lab at the University supervised the identification and contributed to the analysis of these genetic variants.

Once the 100,000 genomes have been collected and sequenced, the data will be publicly available as a controlled dataset. As a result, experts investigating topics from heart disease to human evolution can easily access the genome sequences.

“One of the real gaps in human genetics studies of disease has been the underrepresentation of non-Europeans,” Charles Farber, associate professor of public health sciences, said in an email to The Cavalier Daily. “The work of the GenomeAsia 100K Consortium … provided critical insight into the extent and nature of genome variation in individuals of Asian ancestry and will be critical in making disease genetic studies more inclusive of all global populations.

Ani Manichaikul, assistant professor of public health sciences in the Center for Public Health Genomics, expressed enthusiasm for the GenomeAsia 100K Project. She claimed that the additional genetic information could augment her research as part of the Multi-Ethnic Study of Atherosclerosis, a cardiovascular disease where fatty deposits accumulate and potentially block arteries. The study currently focuses on Caucasian, African American, Hispanic and Chinese American individuals.

“The GenomeAsia project is very useful because there are some instances where particular genetic variants are only observed in particular genetic groups,” Manichaikul said. “Those markers can be unique to those sequenced through the project, which means we would not have necessarily have observed those particular variants otherwise.”

Manichaikul also suggested that expanding existing repositories of hereditary statistics would improve methods of assigning people risk scores for diseases based on their DNA. The National Human Genome Research Institute describes “polygenic risk score,” which indicates a person’s likelihood of certain diseases based on the presence of mutations known to be associated with a given disorder. Companies such as 23andMe have started to provide consumers with this metric, but without a comprehensive database of genomes from different populations, score reliability can decrease.

Since indicators of genetically-linked conditions often appear in certain alleles, or different versions of a gene, knowing whether one has a disease marker can help patients take preventative measures if need be. However, in the absence of comprehensive information on the range of disease markers that appear in different ethnicities, whole populations may lack the potential benefits of this burgeoning healthcare statistic.

“The only way we can create risk prediction models that are accurate across populations is if we also have corresponding databases available with individuals that represent that diversity,” Manichaikul said.

Following the findings in the preliminary study, GenomeAsia 100K Project collaborators will continue to sequence more genomes of Asian individuals. The hope is that, once researchers have access to the data, insights from 100,000 genomes will drive the development of new therapeutic strategies that will benefit people around the world.

“I would like more researchers to have access to this data,” Ratan said. “This is a resource. We’re working to establish these reference datasets, and we would definitely like them to be used.”