From a fertilized egg, all our cells acquire mutations at all times, till the end of life. Most of the mutations are repaired by our body, but some remain in our genome and get passed from cell to cell during embryonic development, upon tissue self-renewal, or after environmental exposure. Genome mosaicism reflects the phenomenon that cells from the same zygote have different genomic sequences.

Unlike other types of mutations that appear in all cells of the body, mosaic mutations are difficult to detect due to the low presentations in samples we can obtain. High accuracy and high sensitivity low-fraction detection methods, both experimental and computational ones, are in high demand for this field.

Patterns of genomic mosaicism, as a combinatory consequence of various mutation procedures as described above, could help us understand the biological processes. For example, mosaic mutations shared between different tissues could serve as markers to trace when two different cell populations shared a common progenitor, which largely remained unsolved in human development.

Mosaicism has been reported to directly contribute to hundreds of documented human disorders. Many disorders related to genomic mosaicism have an obvious mosaic nature, such as focal epilepsies, patchy skin, or bone disorders that only affect some, but not all of the cells. There are, however, disorders caused by mosaic mutations that are not so obvious to suspect. 

Mosaic mutations can also be transmitted to the next generation, by definition, only part of the cells carrying the mutation might lead to severe consequences for the next generation. Thus understanding genomic mosaicism between generations will help us understand the genomic health of ourselves and our children.

Lineage markers with dye, genetic barcodes, or isotope pulse-chase have been used to study the development of model organisms for decades. These interventions, however, are not suitable for human development. Through embryonic development, body growth, and tissue renewal, somatic mutations accumulate across the genome, if mutations fail to be repaired, they will be inherited by daughter cells and serve as neutral lineage markers for development. By using these 'molecular paints' in our body, we consider mosaic variant as a unique barcode to reconstruct human development and find important developmental clonal distributions that might be unique to humans.

Detectable mosaic variants in the parental germline might be inherited by the offspring and cause a severe impact on the children's health. One of the major research interests of the Yang Lab is how parental germline mosaicism, especially sperm mosaic mutations, is affecting the health of the next generation. On the other hand, male-driven evolution is a fundamental genetic driving force of evolution and speciation, understanding the impact of genomic stability between generations will help us to understand how we are humans, and where are we going. We are employing state-of-the-art sequencing and data mining technologies to profile mosaic mutations from sperm in order to understand how environments, aging, and lifestyles are affecting the human sperm genome and shaping the mutational landscape.