Year: 2015
Type: dissertation
Abstract: Defective cilia, hair-like organelles that protrude from the cell membrane, cause diverse human diseases. The Quarmby lab previously used the unicellular alga, Chlamydomonas reinhardtii, to uncover three genes involved in the ciliary stress response known as deflagellation. They showed that defects in a related gene in humans underlie a severe form of juvenile onset polycystic kidney disease. We postulated that rare or subtle variants in additional disease genes could be uncovered by using a more sensitive genetic screen. Armed with advances in whole genome sequencing and an enhanced enrichment protocol, we recovered multiple alleles of previously isolated genes and several alleles of three novel deflagellation genes. We identify the previously elusive ADF1 as TRP15, a putative cation channel activated by intracellular acidification. We also identify the novel deflagellation genes ADF2 as a putative Ins(1,3,4)P3 5/6 Kinase, ADF5 as FAP16 and ADF4 as a glycosyltransferase exhibiting a novel starvation-specific deflagellation defect.
Source: Summit (Simon Fraser University)
Author: Fabian Meili
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2509590011