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NHGRI-Related NewsChromosome 12 Annotated Sequence CompleteHOUSTON - Wed., Mar. 16, 2006 - Researchers from Baylor College of Medicine's (BCM) Human Genome Sequencing Center (HGSC) put the "final period" to the genetic "sentence" of chromosome 12 when they published its annotated sequence as part of a report in the current issue of the journal Nature. The work involved collaboration with the Harvard Medical School-Partners Healthcare Center for Genetics and Genomics (HPCGG) and was funded by the National Human Genome Research Institute of the National Institutes of Health. "It is the culmination of 15 years of work mapping and sequencing this chromosome, which contains many disease loci of interest," said Dr. George Weinstock, co-director of the HGSC. "We took the chromosome 12 DNA sequence and had 15 to 20 people look at it in excruciating detail," said Dr. Steven Scherer, associate professor in the BCM Human Genome Sequencing Center and the paper's lead author. Both he, Weinstock and Dr. Richard Gibbs, the Center's director, are members of the faculty of the BCM Department of Human and Molecular Genetics. Gibbs is the senior author on the paper."This paper is the summary of that work, looking at the highest quality DNA sequence for chromosome 12 with the most computational power and an extraordinary manual annotation effort (interpreting the sequence information). It improves on all the analyses done before," said Weinstock. Starting with a "map" of markers called sequence tagged sites (STS), generated by the group from Harvard, the collaborators then sequenced and annotated 132 million nucleotides - the building blocks of DNA. They found that the chromosome contains more than 1400 genes. Among these is a gene ETV6 associated with various types of leukemias. It also contains one of the longest stretches of DNA that has remained intact through much of evolution, said Scherer. "Going back to the 'out of Africa time' and the different lineages of
the human race, this section of the chromosome has been preserved intact,"
said Weinstock. The chromosome is of high interest because it is fairly dense in disease-related genes, particularly those involved with cancer. It also contains the gene for CD4, the receptor that allows HIV, the virus associated with AIDS, entry into the T-lymphocytes, starting the process of disabling the body's immune system. Much of chromosome 12 was completed with the old model of sequencing in which detailed maps were generated that gave researchers reference points. They then could sequence short stretches of DNA and reassemble the chromosome based on those reference points. Later technology called shotgun sequencing and computer advances allowed scientists to speed the sequencing process and skip the step of generating the detailed map. Chromosome 12 was formed from a reciprocal rearrangement of two ancient chromosomes. This means that pieces of each of the ancient chromosomes broke off and joined to the other chromosome. In this case, chromosomes 12 and 22 were formed from these ancestral chromosomes. Lemurs, a distantly related primate, have the ancient chromosome arrangement, while humans and more closely related primates have chromosomes 12 and 22. Chromosome 12 also appears to be the most slowly evolving of all the chromosomes. Already, the BCM team has built on the chromosome 12 sequence, mapping over 125,000 genetic variations on it as part of the International HapMap Project, that mapped human variation, also known as haplotypes, across the human genome. "Even though we just published this paper, we are now using new technologies to dig deeper and find genes we missed," said Scherer. "We want to know every gene on this chromosome." He predicts they will find just a few more protein-coding genes, but regulatory elements present an exciting new challenge. "You never know if variation in one of those will explain a human disease," he said. Contact Ross Tomlin, Baylor College of Medicine
Last Reviewed: August 4, 2008 |
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