The discovery of the gene's normal function and that its only major role involves the mammary glands suggests that drugs that might be developed in the future to treat it could also be given to leukemia patients with few serious side effects.

A report on this finding appears in the July 19 online posting of the August 6 issue of Molecular and Cellular Biology.

The researchers made their discovery while trying to determine the normal functions of a gene called MKL1 (megakaryoblastic leukemia 1), which is part of a mutation that causes acute megakaryoblastic leukemia (AMKL) in children, according to Stephan Morris, M.D., a member of Pathology and Oncology at St. Jude. AMKL is a leukemia in which megakaryocytes -- the bone marrow cells that normally produce the blood platelets that control blood clotting -- reproduce uncontrollably. The leukemia mutation, caused by the fusion of MKL1 to the gene RBM15, forms the RBM15-MKL1 fusion gene, according to Morris. AMKL resulting from this mutation usually has only a 20-25 percent survival rate.

The other authors include Yi Sun (lead author), Kelli Boyd, Wu Xu, Jing Ma, Carl Jackson, Amina Fu and Zhigui Ma (St. Jude); Jonathan Shillingford, Gertraud Robinson and Lothar Hennighausen (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.); and Johann Hitzler (The Hospital for Sick Children, Toronto, Canada).

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A final set of sequencing targets was chosen to address the question: What genes and other genomic features were responsible for the origin of multi-celled organisms? More than 1 billion years ago, two of the major multi-cellular groups of organisms (fungi and animals) shared a single-celled ancestor. This project targets ten of the earliest branches of animals and fungi along with some of their single-celled relatives providing, for the first time, comprehensive data to fill gaps in our understanding of animal and fungal evolution. Recent research has shown that some genes in the human genome that are responsible for early animal development arose much earlier than thought, in some cases in single-celled organisms. Therefore, this set of ten targets is likely to reveal the origins of other genes important for multi-cellularity in all such animals, including humans. The ten targets, all of which involve relatively small genomes, include six to be sequenced at high-density genome coverage: Capsaspora owczarzaki; Sphaeroforma arctica; an Amastigomonas species; a Salpingoeca or Codosiga species; Allomyces macrogynus; and Nucleria simplex; and four to be sequenced at low-density genome coverage: Amoebidium parasiticum; Mortierella verticilllata; Spizellomyces punctatus; and a Stophanoeca or Acanthocoepis species.

NHGRI's Large-Scale Sequencing Research Network also includes a portfolio of medical sequencing projects. These projects are designed to use high-throughput sequencing resources to lead to significant medical advances. As more is learned from sequencing and other studies about the genomic contribution to disease, and as the cost of obtaining sequence information decreases, genomic sequence information will become ever more important both for medical research and for providing medically relevant information to individuals. When it becomes affordable for an individual's genome to be fully sequenced, genomic information will allow estimates of future disease risk for individuals, as well as improve prevention, diagnosis, and treatment.

Projects given the highest priority will use large-scale sequencing over the next few years to identify the genes responsible for dozens of relatively rare, single-gene (autosomal Mendelian) diseases; sequence all of the genes on the X chromosome from affected individuals to identify those involved in sex-linked diseases; and to survey the range of variants in genes known to contribute to some common diseases.

An example of a medical sequencing project launched last year is The Cancer Genome Atlas (TCGA) pilot project, a groundbreaking effort between NHGRI and the National Cancer Institute that seeks to systematically characterize the genetic changes that occur in cancer. Information on TCGA is available at cancergenome.nih.

Sequencing work on approved targets are carried out by the NHGRI-supported, Large-Scale Sequencing Research Network, which consists of five centers: Agencourt Bioscience Corp., Beverly, Mass.; Baylor College of Medicine, Houston; the Broad Institute of MIT and Harvard, Cambridge, Mass.; the J. Craig Venter Institute, Rockville, Md.; and Washington University School of Medicine, St. Louis. Assignment of new organisms to a specific center or centers will be determined at a later date.

NHGRI's process for selecting sequencing targets begins with three working groups comprised of experts from across the research community. Each of the working groups is responsible for developing a proposal for a set of genomes to sequence that would advance knowledge in one of three important scientific areas: to identify areas in genetic research where the application of high-throughput sequencing resources would rapidly lead to significant medical advances; understanding of the human genome; and understanding the evolutionary biology of genomes. A coordinating committee then reviews the working groups' proposals, helping to fine-tune the suggestions and integrate them into an overarching set of scientific priorities. The recommendations of the coordinating committee are reviewed and approved by one of NHGRI's advisory groups, The National Advisory Council for Human Genome Research, which in turn forwards its recommendations to NHGRI leadership. For more on the selection process, go to: www.genome/Sequencing/OrganismSelection.

A complete list of organisms and their sequencing status can be viewed at www.genome/10002154. High-resolution photos of many of the organisms being sequenced in NHGRI's Large-Scale Sequencing Program are available at: www.genome/10005141.

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