HSC-Institute Of Biosciences And Technology Researchers Learn About Role Of Mutated DNA Repeats In Diseases Like Cancer

Main Category: Genetics
Also Included In: Cancer / Oncology;  Biology / Biochemistry
Article Date: 26 Aug 2008 - 0:00 PST

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Researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology in Houston have uncovered new information about the role of certain mutated segments of DNA in forming diseases like cancer. This finding could someday lead to therapies targeting the mutated DNA segments.

The study, "Abundance and Length of Simple Repeats in Vertebrate Genomes are Determined by their Structural Properties," is currently available online in Genome Research and will be in an upcoming issue of the journal. It is available at http://www.genome.org.

"Researchers knew that some DNA repeats are found to be very abundant in the human genome - the human body's genetic map - whereas others are extremely rare and sometimes absent, but they did not know why," said Albino Bacolla, Ph.D., research associate in the Center for Genome Research and study lead author.

In their study, Dr. Bacolla and his colleagues found that over time, DNA structure and base stacking (where the rings of DNA lie on top of each other) determine the number and length of short DNA repeats (microsatellites) in the vertebrate genome. They also learned the differing microsatellite lengths may lead to disease because the different lengths could regulate gene expression and protein function, contributing to or perhaps hampering the cellular regulatory makeup.

Dr. Bacolla said that he and his colleagues found that some DNA repeats are like a gymnast; they can twist in strange ways and form small structures that look like a cross (cruciforms), and these cruciforms are believed to be an integral part of processes leading to cancer. Cells think that these structures are not part of their DNA and chop them off. So, over millions of years, these sequences become very rare or are lost altogether from the genome.

The study authors found short DNA repeats called microsatellites are hallmarks of cancer. Abundant in the genome of humans and other vertebrates, microsatellites - when unstable - could lead to cancer. Microsatellite instability occurs when cells contain mutations in DNA repair genes. Some of these sequences accumulate errors and become longer or shorter.

Studies have found that variation in sequence length is a key factor in several cancers including colorectal, endometrial, ovarian and gastric. Variations in sequence length also can transfer the susceptibility for inherited diseases over generations.

Different people generally have a different number of repeats at a particular site within their genome, and those individuals with the "wrong" number of repeats are more likely to develop diseases like asthma, endometriosis and breast cancer. Other conditions that could develop are a shortage of oxygen to the brain, pneumonia in the elderly and autoimmune diseases.

Robert D. Wells, professor and director of the Center for Genome Research and senior author, said: "This genetic discovery by Dr. Bacolla and his associates reveals a simple and elegant molecular explanation at why chromosomes, our genetic material, contain certain types of repeating sequences. Thus, new insights are established into evolution, or how we got to be the way we are."

Other contributors to the Genome Research study were Jacquelynn E. Larson, technician in the Center for Genome Research; Jack R. Collins, National Cancer Institute Advanced Biomedical Computing Center; Jian Li and Aleksandar Milosavljevic, Baylor College of Medicine Department of Molecular and Human Genetics and Human Genome Sequencing Center; and Peter D. Stenson and David N. Cooper, Cardiff University Institute of Medical Genetics.

Research was supported by the National Institutes of Health, National Cancer Institute, Friedreich's Ataxia Research Alliance, Seek-a-Miracle Foundation, the Robert A. Welch Foundation and BIOBASE GmbH (Biological Databases).

The Texas A&M Health Science Center provides the state with health education, outreach and research. Its seven colleges located in communities throughout Texas are the Baylor College of Dentistry in Dallas, the College of Medicine in College Station and Temple, the College of Nursing in College Station, the Graduate School of Biomedical Sciences, the Institute of Biosciences and Technology in Houston, the Irma Lerma Rangel College of Pharmacy in Kingsville, and the School of Rural Public Health in College Station.

Texas A&M Health Science Center