BACKGROUND: Isolated GnRH Deficiency (IGD) is a rare Mendelian disorder, characterized by absent puberty and infertility. Over 30 causal IGD genes have been discovered, yet only 30-35% of IGD cases have a proven genetic etiology, highlighting the importance of new discovery methods. Homozygosity mapping, traditionally used to detect autozygous segments in inbred populations, has recently proven useful for gene discovery in outbred populations.
METHODS: Strict quality control (QC) metrics for the SNP genotyped cohort and controls were used. Overall, 653 European IGD probands and 1,911 European controls remained. After pruning, 206,012 SNPs remained. Runs of Homozygosity (ROH) were found and a burden analysis was performed. Areas of known IGD genes, Expression Quantitative Trait Loci (eQTLs) of known genes and novel regions predicted to be associated with IGD were explored.
RESULTS: While there was no statistical difference between the ROH burden in cases vs. controls, there was an unexpected trend towards a greater burden in the controls. Of the known gene locations and their eQTL regions, there was a trend in cases having a higher representation of ROHs within these regions. Four ROH regions unique to cases only were also discovered. None of the individuals had a variant in the coding genes found in these regions.
CONCLUSIONS: SNP markers are found in coding regions and non-coding regions. This allows for a preview of potential disease causing variation in the non-coding region. Even though no coding gene of interest was found, the non-coding parts of the identified regions are of significant interest.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/31235 |
| Date | 12 July 2018 |
| Creators | Kutateladze, Anna Andrea |
| Contributors | McKnight, James C., Crowley Jr., William F. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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