Unraveling the Gene Mystery

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  In an experiment, scientists exchange the microorganisms of a fat mouse’s intestinal tract with those of a thinner counterpart. Over a period of time they feed both the same amount of food, after which, the fat mouse turns thin while the once slim one grows fat.
  The procedure is conducted by a research team headed by Yang Huanming, an academician from the Chinese Academy of Sciences(CAS) and Chairman of the Shenzhen branch of the Beijing Genomics Institute (BGI).“There are more than 170 kinds of bacteria in our bowels,” Yang said. “Whether you are fat or not is to a large extent determined by your genes.”
  Yang’s research has brought new hope for those battling the bulge. However, his research goes even further.
  On April 14, 2003, scientists from China, the United States, Japan, Germany, France and Britain announced they had completed sequence mapping of the human genome, marking the end of the Human Genome Project (HGP) started in 1990. The group of Chinese experts, led by Yang, played an integral part in the research until August 26, 2001.
  Although each scroll of human genome, the most complete polymorphism maps in the world, consists of 23 pairs of chromosome and about 3 billion DNA base-pairs, differences between each are common.
  Genetic polymorphism refers to the difference in genes from one person to another. In fact, 99 percent of people share the same gene structure. However, it is the tiny 1-percent difference that leads to varied disease susceptibility and reactions to medicine and environment.
  DNA, which carries genetic information, is often called the gene that decides one’s height, skin color, disease susceptibility, etc., while the genome refers to all of an organism’s genes. Human beings have only one genome, which consists of 50,000 to 100,000 genes.
  “In order to unravel the mystery of life and heredity, we need to start by sequencing genes and working out their functions,” Yang said.
  The HGP aims to investigate genes via sequencing, locating them on the chromosome and figuring out the function of proteins produced by each, enabling humans to discover themselves at the molecular level.
  However, the completed map of the human genome sequence falls short of Yang’s expectations.
  “Scientists generally think there is only a 0.1-percent difference in genes between any two people,” Yang said. “However, we recently discovered more than 10 million gene variants, among which 8 million were previously unknown.”


   Application to medicine
  With the help of the gene map, doctors can now prevent and cure diseases by spotting gene variants. It also lays a foundation for combating fatal diseases such as cancer and HIV/AIDS.
  “A mutant gene can be prevented from causing disease by a simple switch in lifestyle. In the meantime, medicine strives to eventually cure the effects of malfunctioning genes,”Yang explained.
  He said that researchers from around the world will soon finish sequencing and analysis based on the genomes of 100,000 people.
  At the EuroScience Open Forum Dublin 2012 in July, Yang pointed out in his speech entitled Genomics in the Century of Biology that gene sequencing will encompass more species and move from basic research to medical application, laying a basis for future personalized medicine.
  “We have discovered an anti-HIV gene in caucasians,” Yang said. In fact, this is only one result of the 1,000 Genomes Project, launched on May 10, 2008, by the Shenzhen branch of the BGI, the Wellcome Trust Sanger Institute in Cambridge and the National Human Genome Research Institute in Bethesda, the United States.
  Two years later, Nature magazine published a cover story celebrating the great achievements of the 1,000 Genomes Project, with Science magazine reporting on its progress in gene research technology and hailing it as a new era.
  Scientists all agree that cancer is a genetic problem. Among the approximate 100,000 genes in each human cell, the proto-oncogene is most responsible for the illness while the recessive onco-gene can prevent it. A balance between the two genes assures health, but when carcinogenic factors cause the protooncogene to turn into an oncogene or when the vitality of the tumor suppressor gene is weakened or lost, cancer becomes inevitable.
  Scientists say human health is further determined by the quality of bacteria and fungi genes in our bodies, which assist in the operation of the human system. “Children born via natural births have a stronger immunity than those born by caesarean sections due to sufficient healthy bacteria inoculation during the former,” Yang said.
   The nation’s contribution
  China managed to win a 1-percent research stake in the HGP thanks to Yang’s efforts.
  “Gene sequencing is a hard task that involves biological and information technologies,” he said. “You cannot conduct large-scale sequencing using expensive machinery alone.”   When the CAS established its Gene Center in 1998—currently the BGI—most of the HGP had already been distributed among the five developed countries involved. Germany, the last country to join the project, only received a 2-percent share while many famous research institutes failed to come on board.
  Yang donated over 1 million yuan($158,700) to the gene center to make up for a shortage in funds while his hometown, Leqing City in east China’s Zhejiang Province, put 8 million yuan ($1.27 million) toward research. In addition, Shunyi District of Beijing offered a 3,800-square-meter house as a lab.
  Alongside his colleagues, Yang made a breakthrough less than half a year later when a gene sequencing report submitted to the HGP over the Internet revealed a margin error of only 0.0006 percent, a strong indication of the team’s ability.
  Passing an oral defense of his research in front of the Human Genome Organization at Cambridge University, Yang won a 1-percent share in the HGP, including China in the project.
  China eventually came to share an additional 10-percent stake in the International HapMap Project, which studies the difference between black and white people in efforts to prevent hereditary diseases and realize personalized medicine.
  Yang and his fellow scientists recently completed gene sequencing of several livestock and plant species including rice, pandas, chickens and pigs, entering the world’s top echelon of research. “Genomics has transformed people’s conception of life and of themselves within the span of only a few years, making a considerable contribution to progressive research methods,” he noted.
   Foreign collaborations
  Joining the HGP has enabled China to become one of the few countries capable of independent gene sequencing.
  When an intestinal infection epidemic broke out in Germany last May, local scientists invited BGI researchers to Europe to help study possible causes. Yang headed a team that completed sequencing of the germ’s genes, which in turn led to identifying the disease.
  In praise of his work, Yang was elected to the German National Academy of Sciences in July and also became a bioethics consultant to U.S. President Barack Obama.
  The BGI has carried out a series of international collaborations earlier this year, signing a Memorandum of Understanding with Affymetrix, Inc., an American company producing GeneChips, in January to develop and commercialize a portfolio of plant, crop and livestock micro arrays for genotyping analysis. BGI has also worked with Lal Teer, a Bangladeshi company selling seeds, to sequence the genome of water buffaloes in March. In October, the institute signed a cooperation contract with GENNET, a Czech biomedical research institute. The two institutes will jointly conduct tests on fetus genes before birth, strengthening the health of newly born babies by sequencing. In addition, the institute is currently conducting gene sequencing of 1 percent of the Danes’ genome.   Yang was forced to drop out of school during the “cultural revolution” (1966-76), conducting “scientific experiments” in his home village by growing mushrooms before finding work at a Leqing canning factory, where he taught fellow employees about cultivating their own fungi.
  “No matter how tired I was during the day, I would read at night,” Yang said. He looked for books all over the city, especially all the English ones he could find.
  “We are lucky to benefit from the current age of genomics,” he stressed.
   Who is Yang Huanming?
  1952: Born in Wenzhou, Zhejiang Province
  1978: Received a bachelor’s degree from Hangzhou University
  1982: Received a master’s degree in biology from the Nanjing Railroad Medical Institute
  1988: Earned his Ph.D at the Institute of Medical Genetics at University of Copenhagen, Denmark, and started his post-doctoral training at the Centre d’Immunologie de Marseille-Luminy (CIML) in France
  1990: Continued post-doctoral training at Harvard Medical School and University of California, Los Angeles
  1998: Appointed chairman of the Gene Center under the Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences (CAS)
  1999: Appointed chairman of the Shenzhen branch of the BGI
  2003: Appointed chairman of the Beijing Genomics Institute
  2007: Elected as academician of the CAS
  2012: Elected as academician of the German National Academy of Sciences
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