Charting the somatic sequence variation within a single human

• Applicant: Dr. Sebastian Pott
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 220073357

In practice it is assumed that all cells within an individual human share the same genome, but this is not true. Throughout growth and development cells and entire cell lineages can accumulate genomic changes due to sporadic mutations and structural rearrangements. As a consequence, the adult body is formed of an intricate genetic mosaic. While large-scale sequencing projects are underway to assess the genetic diversity of human populations, the normal genomic variation within human bodies remains largely unexplored. I aim to characterize the somatic sequence variation within a single human. To this end I propose to combine high-throughput sequencing with laser-capture microdissection to obtain whole-genome sequences of different tissues from a single human body. Specifically, my main objectives are to establish whole-genome sequencing of small cell populations and to obtain and characterize genome sequences from multiple tissues of one individual.Studying somatic sequence variation will likely yield fundamental insights into basic human genome biology with direct implications for diseases. Cancer prevalence varies significantly between tissues. Characterizing types, frequency, and distribution of sequence variants in normal tissues will reveal whether differences in cancer prevalence are reflected by tissue-specific mutation spectra and will potentially also shed light on the role on somatic genome variation in various other processes such as aging. Focusing on one individual is an especially powerful way to uncover tissue-specific mutational spectra since all sequence differences are directly attributable to somatic variation.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Jason Lieb, Ph.D.