As gene sequencing technologies rapidly advance and new genomic data becomes available, so does the need for a better understanding and consensus on which gene changes are relevant to diagnosis and treatment.

With a $8.4 million, four-year grant announced today from the National Human Genome Research Institute, researchers from Baylor College of Medicine and The Stanford University School of Medicine hope to address this need by creating a central resource.

"The Stanford/Baylor effort is designed to maximize our use of computational tools and existing databases to define which genetic changes have strong evidence for being associated with the risk of disease," said Dr. Sharon Plon, principal investigator of the BCM site and a professor of pediatrics and molecular and human genetics at BCM. "Right now, individual testing laboratories are making individual decisions. There is no agreed upon method for ranking genetic changes. Different laboratories may come to different conclusions, with one lab calling a DNA change uncertain and another laboratory calling the same change as disease-causing."

Dr. Carlos Bustamante, professor of genetics at Stanford, will serve as principal investigator of the Stanford site. Researchers from Johns Hopkins University will also serve as collaborators.

Dr. Aleksandar Milosavljevic, professor of molecular and human genetics, and Andrew Jackson, of the Bioinformatics Research Laboratory at BCM will also serve as collaborators on the BCM project site.

Focus on new databases

The overall goal of these projects is to more systematically determine whether we have sufficient evidence to classify a genetic change combining data from many sources, Plon said.

The research team will focus on developing state-of-the-art databases that will allow many different types of data to be combined to achieve this goal. Milosavljevic is directing the development of these computer resources at BCM.

An important focus of the project is to expand knowledge of improving variant prediction (changes in genetic sequences that may be associate with disease risk) in non-white populations.

"Currently, patients who are non-European-Caucasian are more likely to get a genetic test report that is uncertain, because the existing databases have less information about these populations," said Plon.

Bustamante’s work on population genetics in healthy populations from Africa and other international efforts will be a significant asset in helping the team more accurately determine which DNA changes are important for disease and which changes are common in these populations, said Plon.

Genome-scale testing

"This effort is designed to help laboratories that are increasingly doing genome-scale testing," said Plon. "Up until current times, genetic testing laboratories specialized on a subset of genes. They would have local expertise on expected genetic changes for those genes and diseases."

Information sharing should be improved, Plon said.

"With the advent of exome and genome sequencing, laboratories now may identify DNA changes in thousands of different genes," said Plon. "Being able to share the accumulated expertise in the clinical genetic testing laboratories across the United States is crucial to improving genome-scale clinical testing."

The National Human Genome Research Institute also announced two grants to investigators focused on the same overall goal. The investigators of these three grants will comprise the National Human Genome Research Institute’s Clinical Genome Resource (ClinGen).

Baylor has one of the top rated genetics programs in the country. It houses one of three NIH-designated large-scale genome sequencing centers - the Baylor Human Genome Sequencing Center - and offers the most advanced genetic testing resources (including whole exome sequencing) available to physicians internationally through the Whole Genome Laboratory at BCM.