1,000 Genomes Project paints detailed picture of human variation

(Press-News.org) HOUSTON -- (Nov. 1, 2012) – First, there was the single human reference genome completed in 2003. Then there was the HapMap project to identify the common genetic variants occurring in human beings with the first map published in 2005. Now an international consortium has released the first phase of the 1,000 Genomes Project that profiles the rare and common genetic variations in 1,092 people drawn from 14 human populations from Europe, Africa, East Asia and the Americas.

The next phase of the project will include as many as 3,000 individuals, said Dr. Fuli Yu (www.bcm.edu/genetics/index.cfm?pmid=23673 ), assistant professor in the Baylor College of Medicine Human Genome Sequencing Center (www.hgsc.bcm.tmc.edu/), and a leader in the analysis portion of the project. The report appears online in the journal Nature. Dr. Richard Gibbs (www.hgsc.bcm.edu/content/message-director ), director of the BCM Human Genome Sequencing Center, is principal investigator of the project here.

"This project provides the next important step towards understanding the function of the rare genetic variants we see across a wide variety of populations," said Gibbs. "With this underpinning, we can go on to solve the puzzle of how this variation plays a part in human disease and health."

"The impact of this project will be huge," said Yu. "Here we have information on nearly 1,100 people, including their rare and common single nucleotide polymorphisms (SNPs) along with insertions and deletions of the genetic material and large structural variations in the DNA itself." In total, the project has provided a map of 38 million single nucleotide polymorphisms (SNPs or single letter changes in the DNA code), 1.4 million indels (insertions or deletions of nucleotides) and over 14,000 larger deletions.

"This will upgrade the human reference sequence," he said. "It will not be just one linear sequence but one that reflects different 'flavors' in a wide variety of populations."

Groups involved in the project include; the Yoruba in Ibadan, Nigeria; the Han Chinese in Beijing, China; the Japanese in Tokyo, Japan; the Utah CEPH community; the Luhya in Webuye, Kenya; people with African Ancestry in the Southwest United States; the Toscani in Italia; people with Mexican Ancestry in Los Angeles, California; the Southern Han Chinese in China; the British in England and Scotland; the Finnish in Finland; the Iberian populations in Spain; the Colombians in Medellin, Colombia; and the Puerto Ricans in Puerto Rico.

The report captures up to 98 percent the sequences of rare gene variants that occur in at least 1 percent of the population. It is believed that the secret to understanding the genetic contribution to common complex diseases such as cancer, heart ailments and diabetes rests with these rare variants.

The findings in the report indicate that there is a substantial geographic variation in the occurrence of these rare variants. Profiles of rare and common variants vary with different populations. Each person has hundreds of rare "non-coding" variants (DNA that does seem to carry the blueprint for a protein) at sites of the genome that are conserved across the evolutionary landscape.

Yu anticipates that findings will prove important clinically. Some of it is already being used in the BCM genetics laboratories to speed diagnosis, he said.

New tools for such sequencing have been a byproduct of the project, said Yu. His laboratory has developed one such tool called ATLAS 2, which is now being used in the BCM Whole Genome Laboratory.

The project also gives direction on how best to design and analyze studies of disease that make use of genetic sequencing, he said.

### Yu said the BCM Human Genome Sequencing Center was involved in many parts of the project, including; the sequencing of the DNA (Gibbs [Principal Investigator], Huyen Dinh, Christie Kovar, Sandra Lee, Lora Lewis, Donna Muzny, Jeff Reid, Min Wang ); the analysis portion (Gibbs [Principal Investigator], Fuli Yu [Project Leader], Matthew Bainbridge, Danny Challis, Uday S. Evani, James Lu, Donna Muzny, Uma Nagaswamy, Jeff Reid, Aniko Sabo, Yi Wang, Jin Yu ); the exome group (Gibbs [Principal Investigator, Co-chair], Fuli Yu [Project Leader], Matthew Bainbridge, Danny Challis, Uday S. Evani, Christie Kovar, Lora Lewis, James Lu, Muzny, Uma Nagaswamy, Jeff Reid, Aniko Sabo, Jin Yu,); the functional interpretation group (Gibbs [Principal Investigator] , Bainbridge, Muzny, Yu, Jin Yu ) and the data coordination center group (Gibbs [Principal Investigator], Kovar, Divya Kalra, Walker Hale, Gerald Fowler, Muzny, Reid).

Funding for this study came from the Wellcome Trust; the British Heart Foundation; the Medical Research Council; the National Basic Research Program of China; the Chinese 863 program; the National Natural Science Foundation of China; the Shenzhen Key Laboratory of Transomics Biotechnologies; the Shenzhen Municipal Government of China; the Guandong Innovative Research Teem Program; the German Federal Ministry of Education and Research; the Max Planck Society; the Swiss National Science Foundation; the Louis Jeantet Foundation; the Biotechnology and Biological Sciences Research Council; the German Research Foundation; the Netherlands Organization for Scientific Research; the Beatriu de Pinos program; the Israeli Science Foundation; Genome Quebec and the Ministry of Economic Development, Innovation and Trade; the National Institutes of Health; the National Human Genome Research Institute; the National Institute of Allergy and Infectious Diseases; the Coriell Institute for Medical Research; the Sandler Foundation; the American Asthma Foundation; the IBM Open Collaborative Research Program; the A.G. Leventis Foundation; the Wolfson Royal Society; the Howard Hughes Medical Institute and EMBO.

For more information on basic science at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.