Baylor College of Medicine Receives NIH Funding for Somatic Mosaic Research

Somatic mosaicism occurs when somatic cells, or non-germ cells of the body, are genetically different from each other. Although somatic mosaicism can occur in all tissues and is known to cause cancer, the extent of somatic mosaicism in the human genome and its full impact on human health are unknown.

As part of a new National Institutes of Health Common Fund program called the Somatic Mosaic Across Human Tissues (SMaHT) Network, researchers at Baylor College of Medicine are investing a total of $17.8 million over five years to develop cutting-edge tools. Received more than 3 grants. To catalog the degree of somatic mosaicism in different cell types, tissues and life stages and to better understand how somatic mosaicism affects human biology and disease.

“This important program is a comprehensive assessment of the role of somatic mutations in normal human development,” said Wofford Kane, founding director of the Human Genome Sequencing Center at Baylor University and professor of molecular biology. Dr. Richard Gibbs, professor of human genetics, said: “This will be the basis for a full understanding of the role of somatic mutations in all aspects of human disease.”

One of Baylor’s grants is to establish a genome analysis center at Baylor’s Human Genome Sequencing Center. Gibbs will serve as a co-principal investigator on the project, along with Dr. Harsha Dodapaneni, associate professor at the Human Genome Sequencing Center, and Dr. Lui Chen, professor of molecular and human genetics at Baylor University. The center will characterize 550 somatic mutations in his 2,250 tissue samples for the SMaHT program. Sample tissues were obtained from approximately 150 human donors of various ancestral backgrounds and life stages, and various types of tissues such as brain, blood, skin, muscle, colon, spleen, uterus, vas deferens, ovaries, and testes were collected. is taken.

In addition to extensive profiling efforts by SMaHT centers within the network, it is still difficult to study somatic mosaicism using conventional methods and platforms, so it is difficult to accurately determine somatic mosaicism, especially at single-cell resolution. There is a great need for new methods to detect Baylor’s 14 projects within the network, including his two, will focus on developing new techniques to address this problem.

Led by principal investigator Chenghang (Chuck) Zong, Ph.D., an assistant professor of molecular and human genetics at Baylor University and a McNair Scholar, the project is a novel single-cell whole cell gene that enables high-precision, high-coverage detection. We plan to develop genome amplification chemistry. Analysis of somatic mutations in single cells. Comprehensive single-cell data allowed the team to effectively build a phylogenetic tree of sequenced single cells, and to distinguish between cells located in different lineage branches, especially if these cells belonged to the same type of cell. It makes it possible to characterize phenotypic variation. The team will develop a high-throughput platform of technology that can be used broadly within the SMaHT network.

The project, led by Dr. Fritz Sedrazek, Associate Professor and Principal Investigator at the Human Genome Sequencing Center, is a novel approach to studying structural variation in somatic cells based on long-read sequencing using novel algorithms and machine learning approaches. Focus on developing new computational methods. The research team will focus on identifying genome-wide transposon movements and their epigenetic effects. To discover this, the team innovates new algorithms using long read data. All methods will also be available via his SMaHT network.

Other Baylor researchers contributing to this study include Dr. Donna Muzney and Ph.D. Marie-Claude Gingras, Elizabeth Atkinson, Wu Tao.

This work was supported by NIH Common Fund grants (1 UM1 DA058229-01, 1 UG3 NS132132-01, 1 UG3 NS132105-01).

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