Exome Sequencing RevealsAGBL5as Novel Candidate Gene and Additional Variants for Retinitis Pigmentosa in Five Turkish Families

2015 ◽  
Vol 56 (13) ◽  
pp. 8045 ◽  
Author(s):  
Simone Kastner ◽  
Ina-Janine Thiemann ◽  
Gabriele Dekomien ◽  
Elisabeth Petrasch-Parwez ◽  
Sabrina Schreiber ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Candidate Gene ◽  
Exome Sequencing

FC 011KIDNEYNETWORK: USING KIDNEY DERIVED GENE EXPRESSION DATA TO PREDICT AND PRIORITIZE NOVEL GENES INVOLVED IN KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Floranne Boulogne ◽  
Laura Claus ◽  
Henry Wiersma ◽  
Roy Oelen ◽  
Floor Schukking ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Disease ◽  
Candidate Gene ◽  
Exome Sequencing ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Genetic Diagnosis ◽  
Specific Gene ◽  
Sequencing Data ◽  
Exome Sequencing Data

Abstract Background and Aims Genetic testing in patients with suspected hereditary kidney disease does not always reveal the genetic cause for the patient's disorder. Potentially pathogenic variants can reside in genes that are not known to be involved in kidney disease, which makes it difficult to prioritize and interpret the relevance of these variants. As such, there is a clear need for methods that predict the phenotypic consequences of gene expression in a way that is as unbiased as possible. To help identify candidate genes we have developed KidneyNetwork, in which tissue-specific expression is utilized to predict kidney-specific gene functions. Method We combined gene co-expression in 878 publicly available kidney RNA-sequencing samples with the co-expression of a multi-tissue RNA-sequencing dataset of 31,499 samples to build KidneyNetwork. The expression patterns were used to predict which genes have a kidney-related function, and which (disease) phenotypes might be caused when these genes are mutated. By integrating the information from the HPO database, in which known phenotypic consequences of disease genes are annotated, with the gene co-expression network we obtained prediction scores for each gene per HPO term. As proof of principle, we applied KidneyNetwork to prioritize variants in exome-sequencing data from 13 kidney disease patients without a genetic diagnosis. Results We assessed the prediction performance of KidneyNetwork by comparing it to GeneNetwork, a multi-tissue co-expression network we previously developed. In KidneyNetwork, we observe a significantly improved prediction accuracy of kidney-related HPO-terms, as well as an increase in the total number of significantly predicted kidney-related HPO-terms (figure 1). To examine its clinical utility, we applied KidneyNetwork to 13 patients with a suspected hereditary kidney disease without a genetic diagnosis. Based on the HPO terms “Renal cyst” and “Hepatic cysts”, combined with a list of potentially damaging variants in one of the undiagnosed patients with mild ADPKD/PCLD, we identified ALG6 as a new candidate gene. ALG6 bears a high resemblance to other genes implicated in this phenotype in recent years. Through the 100,000 Genomes Project and collaborators we identified three additional patients with kidney and/or liver cysts carrying a suspected deleterious variant in ALG6. Conclusion We present KidneyNetwork, a kidney specific co-expression network that accurately predicts what genes have kidney-specific functions and may result in kidney disease. Gene-phenotype associations of genes unknown for kidney-related phenotypes can be predicted by KidneyNetwork. We show the added value of KidneyNetwork by applying it to exome sequencing data of kidney disease patients without a molecular diagnosis and consequently we propose ALG6 as a promising candidate gene. KidneyNetwork can be applied to clinically unsolved kidney disease cases, but it can also be used by researchers to gain insight into individual genes to better understand kidney physiology and pathophysiology. Acknowledgments This research was made possible through access to the data and findings generated by the 100,000 Genomes Project; http://www.genomicsengland.co.uk.

scholarly journals Whole-exome sequencing reveals POC5 as a novel gene associated with autosomal recessive retinitis pigmentosa

2017 ◽  
Vol 27 (4) ◽  
pp. 614-624 ◽  
Author(s):  
Monika Weisz Hubshman ◽  
Sanne Broekman ◽  
Erwin van Wijk ◽  
Frans Cremers ◽  
Alaa Abu-Diab ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Novel Gene ◽  
Whole Exome

scholarly journals Comparative exome sequencing reveals novel candidate genes for retinitis pigmentosa

EBioMedicine ◽  
2020 ◽  
Vol 56 ◽  
pp. 102792
Author(s):  
Zhen Yi ◽  
Jiamin Ouyang ◽  
Wenmin Sun ◽  
Shiqiang Li ◽  
Xueshan Xiao ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Candidate Genes

scholarly journals Exome sequencing revealed Notch ligand JAG1 as a novel candidate gene for familial exudative vitreoretinopathy

2019 ◽  
Vol 22 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Lin Zhang ◽  
Xiang Zhang ◽  
Huijuan Xu ◽  
Lulin Huang ◽  
Shanshan Zhang ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Exome Sequencing ◽  
Notch Ligand ◽  
Familial Exudative Vitreoretinopathy

A family case with germline TSC1 and mtDNA mutations developing bilateral eosinophilic chromophobe renal cell carcinomas without other typical phenotype of tuberous sclerosis

2018 ◽  
Vol 71 (10) ◽  
pp. 936-943 ◽  
Author(s):  
Hiromasa Sakamoto ◽  
Toshinari Yamasaki ◽  
Takayuki Sumiyoshi ◽  
Noriaki Utsunomiya ◽  
Masashi Takeda ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Candidate Gene ◽  
Tuberous Sclerosis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Renal Cell ◽  
Renal Cell Carcinomas ◽  
Whole Exome ◽  
Family Case ◽  
Gene Alterations

AimWe examined the genetic alterations in a mother and son with multiple eosinophilic chromophobe renal cell carcinomas (chRCCs) showing no other features.MethodsGermline DNA and bilateral renal cell carcinoma DNA were genetically analysed by whole-exome sequencing. Candidate gene alterations in the first patient’s germline were investigated in her child’s germline and the chRCCs.ResultsWe detected several germline gene alterations in the mother. Among the identified alterations, TSC1 and mitochondrial DNA mutations were also confirmed in her son. Regarding somatic alterations in bilateral chRCCs, no common candidate gene alteration was found.ConclusionTo the best of our knowledge, this is the first report of whole-exome sequencing revealing bilateral eosinophilic chRCCs associated with tuberous sclerosis complex in a family case without classical phenotype. These results suggest that germline TSC1 and mitochondrial DNA gene mutations may be involved in the development of chRCCs in some cases.

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