Shenzhen, China-An international team, consisting of scientists from University of California San Diego, BGI and other institutes, has investigated the entire DNA code of Andean individuals with chronic mountain sickness (CMS), or Monge’s disease to unravel the puzzle of genetic mutations associated with CMS from whole-genome level. The study published online today in American Journal of Human Genetics, provides evidence to support whole-genome sequencing as an ultimate approach to advance the understanding of the genetic basis of CMS and its treatment.
More than 140 million humans have permanently settled on high altitude regions in various locations around the world, such as the Ethiopian plateau in East Africa, the Tibetan plateau in Asia and the Andes Mountains in South America. These native or long-time residents are likely to be affected by CMS, especially those living over 3000 meters and many of them are desperate to suffer the symptom. The team decoded the genomes of some local residents to unravel the genetic mechanism and develop safer treatments for CMS.
In this study, a total of 20 Andean individuals were sequenced, including ten individuals with CMS and ten not on the CMS as controls. Researchers surveyed the entire spectrum of variations with high efficiency, and found 11 regions that show significant differences in haplotype frequencies consistent with selective sweeps. In these regions, two genes, ANP32D and SENP1, were found that they have significantly increased expression in the CMS individuals compared to the non-CMS ones, and play an essential role in hypoxia tolerance.
The genomic data also enable researchers to better understand the mechanisms of human adaptation to hypoxia. They speculated that the increased expression of SENP1 may play a role in the basic pathogenesis of polycythemia in CMS individuals. ANP32D acts as an oncogene, which may alters cellular metabolism in a fashion that is similar to that of cancer cells, especially given that such cells can flourish in low oxygen conditions.
“Whole-genome sequencing serves as an ultimate approach to advance the understanding of the genetic basis of CMS,” said, Xin Jin, project manager of BGI, “Our study provides an unbiased framework to identify and validate the genetic basis of adaptation to high altitudes, and highlight the potentially targetable mechanisms for CMS treatment.”
Dr. Dan Zhou and Dr. Gabriel Haddad, the leading scientists of this project from University of California San Diego, said, “Hypoxia is a common pathogenic factor in many human diseases. Understanding the mechanisms underlying hypoxia tolerance is essential to develop novel therapeutic strategies to treat these clinical conditions. Current study combining the power of whole genome sequencing, in vitro human cell model and in vivo Drosophila model allowed us not only to identify candidate genes that are associated to hypoxia adaptation but also to functionally evaluate their contributions to the trait. This unique unbiased framework has the potential to be applied to identify causal mutations in human diseases.”
BGI was founded in Beijing, China, in 1999 with the mission to become a premier scientific partner for the global research community. The goal of BGI is to make leading-edge genomic science highly accessible, which it achieves through its investment in infrastructure, leveraging the best available technology, economies of scale, and expert bioinformatics resources. BGI, and its affiliates, BGI Americas, headquartered in Cambridge, MA, and BGI Europe, headquartered in Copenhagen, Denmark, have established partnerships and collaborations with leading academic and government research institutions as well as global biotechnology and pharmaceutical companies, supporting a variety of disease, agricultural, environmental, and related applications.
BGI has a proven track record of excellence, delivering results with high efficiency and accuracy for innovative, high-profile research: research that has generated over 200 publications in top-tier journals such as Nature and Science. BGI’s many accomplishments include: sequencing one percent of the human genome for the International Human Genome Project, contributing 10 percent to the International Human HapMap Project, carrying out research to combat SARS and German deadly E. coli, playing a key role in the Sino-British Chicken Genome Project, and completing the sequence of the rice genome, the silkworm genome, the first Asian diploid genome, the potato genome, and, more recently, have sequenced the human Gut Metagenome, and a significant proportion of the genomes for the 1000 Genomes Project.
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