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Comments on Keenan, Samuel et al. (2015) International Worm Meeting "Identification of novel Kallmann syndrome genes by fluorescence activated cell sorting and expression profiling." (0)
Overview
Keenan, Samuel, Steves, Alyse, Voyles, Taylor, Chibuzo, Joy, Schwieterman, Alicia, & Hudson, Martin (2015). Identification of novel Kallmann syndrome genes by fluorescence activated cell sorting and expression profiling presented in International Worm Meeting. Unpublished information; cite only with author permission.
The kal-1/anosmin gene encodes the secreted extracellular matrix protein anosmin-1, which is required for axon pathfinding and branching during early development. In humans, mutations in the kal-1/anosmin gene lead to X-linked Kallmann syndrome (KS), which is characterized by loss of the ability to smell and impaired sexual development. KS is a polygenic trait, and 20 genes have been associated with this disease to date. Despite that, only 35% of affected individuals exhibit abnormalities in genes that have been shown to cause KS, suggesting that other genes may be involved in this disease. We hypothesize that genes required for the transcriptional control of known KS genes may be KS candidates in their own right. Based on this hypothesis, loss-of-function mutations in genes regulating kal-1 transcription may present similar phenotypes to kal-1 loss-of-function mutations. In addition, we might expect to see changes in the expression pattern of a kal-1-GFP transgene.We have used modENCODE to predict which transcription factors might be involved in kal-1 gene regulation. Preliminary data indicates that cnd-1, the C. elegans ortholog of human NeuroD, may be required for kal-1 transcription in a subset of kal-1-positive cells. In parallel with this, we have also adopted a fluorescence activated cell sorter (FACS) approach to isolate GFP-positive and negative cells from a kal-1-GFP C. elegans strain. Quantitative reverse-transcription polymerase chain reaction assays confirm that we are enriching for kal-1 and GFP transcripts in our GFP-positive samples. Our next step is to perform a transcriptome analysis on mRNA extracted from the GFP-positive and negative populations to assist in identifying the transcription factors that are present in these cell populations. High-ranking candidates in the GFP-positive dataset will be validated using TF loss-of-function mutants and C. elegans assays of KS.
Affiliation:
- Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA