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Archive - May 28, 2012

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Variations in Single Gene Can Lead to Too Little or Too Much Growth

UCLA geneticists, together with collaborators, have identified the mutation responsible for IMAGe syndrome, a rare disorder that stunts infants' growth. The twist? The mutation occurs on the same gene that causes Beckwith-Wiedemann syndrome, which makes cells grow too fast, leading to very large children. Published online on May 27, 2012 in Nature Genetics, the UCLA findings could lead to new ways of blocking the rapid cell division that allows tumors to grow unchecked. The discovery also offers a new tool for diagnosing children with IMAGe syndrome, which until now has been difficult to accurately identify. The discovery holds special significance for principal investigator Dr. Eric Vilain, a professor of human genetics, pediatrics, and urology at the David Geffen School of Medicine at UCLA. Nearly 20 years ago, as a medical resident in his native France, Dr. Vilain cared for two boys, ages 3 and 6, who were dramatically short for their ages. Though unrelated, both children shared a mysterious malady marked by minimal fetal development, stunted bone growth, sluggish adrenal glands, and undersized organs and genitals. "I never found a reason to explain these patients' unusual set of symptoms," explained Dr. Vilain, who is also director of the UCLA Institute for Society and Genetics. "I've been searching for the cause of their disease since 1993." When Dr. Vilain joined UCLA as a genetics fellow, the two cases continued to intrigue him. His mentor, then UCLA geneticist Dr. Edward McCabe, recalled a similar case from his previous post at Baylor College of Medicine. The two scientists obtained blood samples from the three cases and analyzed the patients' DNA for mutations in suspect genes, but uncovered nothing. Drs.

Giant Cells Protect Potentially Deadly Fungus During Infection

Giant cells called "titan cells" created by the fungus Cryptococcus neoformans protect the fungus during infection, according to two University of Minnesota researchers. Kirsten Nielsen, Ph.D., an assistant professor in the department of microbiology, and recent Ph.D. recipient Laura Okagaki believe their discovery could help develop new ways to fight infections caused by Cryptococcus. The findings will be published in the June 2012 issue of the journal Eukaryotic Cell. Cryptococcus, a fungus frequently found in dust and dirt, is responsible for the deaths of more than 650,000 AIDS patients worldwide each year. It is also a potentially deadly concern among chemotherapy and organ transplant patients. Currently, Cryptococcus causes more annual deaths in sub-Saharan Africa than tuberculosis. "While most healthy individuals are resistant to Cryptococcus infections, the fungus can cause deadly disease for those with already weak immune systems," said Dr. Nielsen. When inhaled, Cryptococcus can cause an infection in the lungs. This infection can spread to the brain and result in meningitis, an often-deadly inflammation of the brain and spine. Drs. Nielsen and Okagaki found that titan cells, or Cryptococcus cells ten to twenty times the size of a normal cell, are too large to be destroyed by the body's immune system. The researchers also found that the presence of titan cells can protect all Cryptococcus cells in the area, even the normal-sized Cryptococcus cells. "This tells us that titan cell formation is an important aspect of the interaction between the human/host and the organism that allows Cryptococcus to cause disease," said Dr. Nielsen.

DNA Replication Protein Also Has a Role in Mitosis and Cancer

The foundation of biological inheritance is DNA replication – a tightly coordinated process in which DNA is simultaneously copied at hundreds of thousands of different sites across the genome. If that copying mechanism doesn't work as it should, the result could be cells with missing or extra genetic material, a hallmark of the genomic instability seen in most birth defects and cancers. University of North Carolina (UNC) School of Medicine scientists have discovered that a protein known as Cdt1, which is required for DNA replication, also plays an important role in a later step of the cell cycle, mitosis. The finding presents a possible explanation for why so many cancers possess not just genomic instability, but also more or less than the usual 46 DNA-containing chromosomes. The new research, which was published online on May 13, 2012 in Nature Cell Biology, is the first to definitively show such a dual role for a DNA replication protein. "It was such a surprise, because we thought we knew what this protein's job was – to load proteins onto the DNA in preparation for replication," said Jean Cook, Ph.D., associate professor of biochemistry and biophysics and pharmacology at the UNC School of Medicine and senior study author. "We had no idea it also had a night job, in a completely separate part of the cell cycle." The cell cycle is the series of events that take place in a cell leading to its growth, replication and division into two daughter cells. It consists of four distinct phases: G1 (Gap 1), S (DNA synthesis), M (mitosis), and G2 (Gap 2). Dr. Cook's research focuses on G1, when Cdt1 places proteins onto the genetic material to get it ready to be copied. In this study, Dr. Cook ran a molecular screen to identify other proteins that Cdt1 might be interacting with inside the cell.

Genome Sequence of Widely Planted Foxtail Millet Completed

BGI, the world's largest genomics organization, in cooperation with Zhangjiakou Academy of Agricultural Science, has completed the genome sequence and analysis of foxtail millet (Setaria italica), the second-most widely planted species of millet. This study provides an invaluable resource for the study and genetic improvement of foxtail millet and millet crops at a genome-wide level. Results of the latest study were published online on May 13, 2012 in Nature Biotechnology. Foxtail millet is an important cereal crop providing food and feed in semi-arid areas. It is the top-one crop in ancient China. It promises to serve as an important model for comparative genomics and functional gene studies, due to its small genome size (~490M), self-pollination, rich genetic diversity (~6000 varieties), complete collection of germplasm, and the availability of efficient transformation platforms. It is also evolutionarily close to several important biofuel grasses, such as switchgrass and napier grass. "The lower yield of traditional cultivars has largely limited cultivation and utilization of foxtail millet," said Dr. Gengyun Zhang, Vice President of BGI. "Hybrid cultivars, recently developed by Professor Zhihai Zhao in Zhangjiakou Agricultural Academy of Science, doubled the yield of foxtail millet. I expect that the results of this study could set an example of applying the genome sequence to better understanding and quicker developing new varieties of a neglected crop with higher yield, better grain quality, and stress tolerance." In this study, researchers from BGI carried out next-generation sequencing and de novo assembly for "Zhang gu," one strain of foxtail millet from Northern China. The final genome assembly was 423 Mb, and 38,801 protein-coding genes have been predicted, of which ~81% were expressed.