RASopathies: Presentation at the Genome, Interactome, and Phenome Levels

Pevec, Urska; Rozman, Neva; Gorsek, Blaz; Kunej, Tanja

doi:10.1159/000445733

Cited by 11 publications

(13 citation statements)

References 21 publications

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“…These clinical entities, for example, comprise hypo-gonadotrophic hypogonadism (Kallmann syndrome—MIM: 308700), where MPS led to the identification of additional candidate genes [ 58 ]. Research progress has been made in the case of Klinefelter syndrome by application of testis transcriptomic analysis [ 59 ] MI is also commonly associated with rare syndromes with maldescended testes where most of the progress in research is again due to the application of MPS and bioinformatics: Noonan—MIM:163950 [ 60 ], Cleidocranial dysplasia—MIM:119600 [ 61 ], Bloom—MIM:210900 [ 62 ] and Silver–Russel syndromes—MIM:180860 [ 63 ]. Likewise, primary ciliary dyskinesia (MIM: 244400) and myotonic dystrophy 1 (MIM: 160900), which are associated in their milder forms with MI, have been subjected to similar research strategies [ 64 , 65 ].…”

Section: Introductionmentioning

confidence: 99%

Recent developments in genetics and medically assisted reproduction: from research to clinical applications

et al. 2017

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Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

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Section: Introductionmentioning

confidence: 99%

Recent developments in genetics and medically assisted reproduction: from research to clinical applications

et al. 2017

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“…The relevance of protein-protein interactions was examined in a study by Cannistraci et al ( 17 ), where such interactions revealed the relation between co-presence of cardiomyopathy and cryptorchidism; two symptoms of the RASopathies. The study by Pevec et al ( 70 ) also provided a baseline for future studies of associations between interactome and phenome in RASopathies, additionally presenting data at genome, interactome, and phenome levels and as an integrated network of all three data types.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Syndromic Cryptorchidism: Data Synthesis of 50 Studies and Visualization of Gene-Disease Network

et al. 2018

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Background: Cryptorchidism is one of the most frequent congenital birth defects in male children and is present in 2–4% of full-term male births. It has several possible health effects including reduced fertility, increased risk for testicular neoplasia, testicular torsion, and psychological consequences. Cryptorchidism is often diagnosed as comorbid; copresent with other diseases. It is also present in clinical picture of several syndromes. However, this field has not been systematically studied. The aim of the present study was to catalog published cases of syndromes which include cryptorchidism in the clinical picture and associated genomic information.Methods: The literature was extracted from Public/Publisher MEDLINE and Web of Science databases, using the keywords including: syndrome, cryptorchidism, undescended testes, loci, and gene. The obtained data was organized in a table according to the previously proposed standardized data format. The results of the study were visually represented using Gephi and karyotype view.Results: Fifty publications had sufficient data for analysis. Literature analysis resulted in 60 genomic loci, associated with 44 syndromes that have cryptorchidism in clinical picture. Genomic loci included 38 protein-coding genes and 22 structural variations containing microdeletions and microduplications. Loci, associated with syndromic cryptorchidism are located on 16 chromosomes. Visualization of retrieved data is presented in a gene-disease network.Conclusions: The study is ongoing and further studies will be needed to develop a complete catalog with the data from upcoming publications. Additional studies will also be needed for revealing of molecular mechanisms associated with syndromic cryptorchidism and revealing complete diseasome network.

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“…Proteomics can make sensitive genome annotations more accurate (Brosch et al., ), as well as confirm novel splice variants seen in RNA‐seq data (Gascoigne et al., ). Recently, an integrated bioinformatics approach was performed to understand the RASopathy class of disorders to identify protein–protein interaction in disease context by integrating genomic, phenomic, and interactome information from HGNC, OMIM, and GeneReviews (Pevec, Rozman, Gorsek, & Kunej, ). Deriving personalized, integrated databases for individual patients can be a robust strategy for clinical molecular diagnosis and therapy.…”

Section: Promise Of Functional Genomics and In Vivo In Vitro Validatmentioning

confidence: 99%

Inferring the effect of genomic variation in the new era of genomics

Chakravorty

Hegde

2018

Human Mutation

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Accurate and detailed understanding of the effects of variants in the coding and noncoding regions of the genome is the next big challenge in the new genomic era of personalized medicine, especially to tackle newer findings of genetic and phenotypic heterogeneity of diseases. This is necessary to resolve the gene-variant-disease relationship, the pathogenic variant spectrum of genes, pathogenic variants with variable clinical consequences, and multiloci diseases. In turn, this will facilitate patient recruitment for relevant clinical trials. In this review, we describe the trends in research at the intersection of basic and clinical genomics aiming to (a) overcome molecular diagnostic challenges and increase the clinical utility of next-generation sequencing (NGS) platforms, (b) elucidate variants associated with disease, (c) determine overall genomic complexity including epistasis, complex inheritance patterns such as "synergistic heterozygosity," digenic/multigenic inheritance, modifier effect, and rare variant load. We describe the newly emerging field of integrated functional genomics, in vivo or in vitro large-scale functional approaches, statistical bioinformatics algorithms that support NGS genomics data to interpret variants for timely clinical diagnostics and disease management. Thus, facilitating the discovery of new therapeutic or biomarker options, and their roles in the future of personalized medicine.

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RASopathies: Presentation at the Genome, Interactome, and Phenome Levels

Cited by 11 publications

References 21 publications

Recent developments in genetics and medically assisted reproduction: from research to clinical applications

Recent developments in genetics and medically assisted reproduction: from research to clinical applications

Molecular Mechanisms of Syndromic Cryptorchidism: Data Synthesis of 50 Studies and Visualization of Gene-Disease Network

Inferring the effect of genomic variation in the new era of genomics

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