The discovery of several novel deflagellation genes and the identification of ADF1

Author: 
Date created: 
2015-12-07
Identifier: 
etd9338
Keywords: 
Cilia
Flagella
Chlamydomonas reinhardtii
Deflagellation
Genetic Screen
Whole Genome Sequencing
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.

Document type: 
Thesis
Rights: 
This thesis may be printed or downloaded for non-commercial research and scholarly purposes. Copyright remains with the author.
File(s): 
Supervisor(s): 
Lynne Quarmby
Department: 
Science: Department of Molecular Biology and Biochemistry
Thesis type: 
(Thesis) M.Sc.
Statistics: