Functional Genetics of Epidermal Mosaic Disease [electronic resource].

9781088320389

Ann Arbor : ProQuest Dissertations & Theses, 2019.

1 online resource (246 p.)

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Genetic mosaicism is the concept that organisms may contain groups of cells that do not have identical genomes, despite being derived from a single cell. When a somatic mutation occurs during development, the affected cell and all of its progeny will carry this mutation. When pathogenic mutations occur within individuals during development patients present with some affected tissue, as well as some unaffected tissue. Perhaps this is most dramatically clear in the skin, where the pathology is visually apparent. By employing next-generation sequencing technology, we are able to identify the causative mutations across a variety of disorders. We gained insight into disorders caused by mutations within the RAS-RAF-MEK pathway. While these genes and specific mutations have been well studied in the context of cancer biology, our findings raise new questions the effects of RAS on the interfolicular and follicular keratinocytes. Further, we found mutations in NEK9 cause nevus comedonicus. The role of NEK9 within the epidermis has heretofore been unstudied. These NEK9 mutations influence follicular differentiation, leading affected follicular keratinocytes to adopt a differentiation status more similar to interfolicular keratinocytes. Identification of these pathogenic variants helps with both a clinical understanding of these disorders and as well as expanding our understanding of epidermal biology.

Dissertations & Theses @ Yale University.

Books / Online / Dissertations & Theses

English

January 17, 2020

Thesis (Ph.D.)--Yale University, 2019.

Yale University. Genetics.