Dataset Information

GeneVetter: a web tool for quantitative monogenic assessment of rare diseases.

ABSTRACT:

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When performing DNA sequencing to diagnose affected individuals with monogenic forms of rare diseases, accurate attribution of causality to detected variants is imperative but imperfect. Even if a gene has variants already known to cause a disease, rare disruptive variants predicted to be causal are not always so, mainly due to imperfect ability to predict the pathogenicity of variants. Existing population-scale sequence resources such as 1000 Genomes are useful to quantify the 'background prevalence' of an unaffected individual being falsely predicted to carry causal variants. We developed GeneVetter to allow users to quantify the 'background prevalence' of subjects with predicted causal variants within specific genes under user-specified filtering parameters. GeneVetter helps quantify uncertainty in monogenic diagnosis and design genetic studies with support for power and sample size calculations for specific genes with specific filtering criteria. GeneVetter also allows users to analyze their own sequence data without sending genotype information over the Internet. Overall, GeneVetter is an interactive web tool that facilitates quantifying and accounting for the background prevalence of predicted pathogenic variants in a population.

Availability and implementation

GeneVetter is available at http://genevetter.org/

Contact

mgsamps@med.umich.edu or hmkang@umich.edu

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Gillies CE

PROVIDER: S-EPMC4643620 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Publications

GeneVetter: a web tool for quantitative monogenic assessment of rare diseases.

Gillies Christopher E CE Robertson Catherine C CC Sampson Matthew G MG Kang Hyun Min HM

Bioinformatics (Oxford, England) 20150723 22

<h4>Unlabelled</h4>When performing DNA sequencing to diagnose affected individuals with monogenic forms of rare diseases, accurate attribution of causality to detected variants is imperative but imperfect. Even if a gene has variants already known to cause a disease, rare disruptive variants predicted to be causal are not always so, mainly due to imperfect ability to predict the pathogenicity of variants. Existing population-scale sequence resources such as 1000 Genomes are useful to quantify th ...[more]

PMID: 26209433

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Project description:BackgroundRare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000. For most of them, clinical symptoms and signs can be observed at birth or childhood. Approximately 80% of all rare diseases have a genetic background and most of them are monogenic conditions. In addition, while the majority of these diseases is still incurable, early diagnosis and specific treatment can improve patients' quality of life. Transplantation is among the therapeutic options and represents the definitive treatment for end-stage organ failure, both in children and adults. The aim of this paper was to analyze, in a large cohort of Italian patients, the main rare genetic diseases that led to organ transplantation, specifically pointing the attention on the pediatric cohort.ResultsTo the purpose of our analysis, we considered heart, lung, liver and kidney transplants included in the Transplant Registry (TR) of the Italian National Transplantation Center in the 2002-2019 timeframe. Overall, 49,404 recipients were enrolled in the cohort, 5.1% of whom in the pediatric age. For 40,909 (82.8%) transplant recipients, a disease diagnosis was available, of which 38,615 in the adult cohort, while 8,495 patients (17.2%) were undiagnosed. There were 128 disease categories, and of these, 117 were listed in the main rare disease databases. In the pediatric cohort, 2,294 (5.6%) patients had a disease diagnosis: of the 2,126 (92.7%) patients affected by a rare disease, 1,402 (61.1%) presented with a monogenic condition. As expected, the frequencies of pathologies leading to organ failure were different between the pediatric and the adult cohort. Moreover, the pediatric group was characterized, compared to the adult one, by an overall better survival of the graft at ten years after transplant, with the only exception of lung transplants. When comparing survival considering rare vs non-rare diseases or rare and monogenic vs rare non-monogenic conditions, no differences were highlighted for kidney and lung transplants, while rare diseases had a better survival in liver as opposed to heart transplants.ConclusionsThis work represents the first national survey analyzing the main genetic causes and frequencies of rare and/or monogenic diseases leading to organ failure and requiring transplantation both in adults and children.

Project description:BackgroundLoneliness, social isolation, and feeling disconnected from society are commonly experienced by parents of children with rare diseases and are, among others, important reasons for special supportive care needs. Social networking platforms are increasingly used for health communication, information exchange, and support. In the field of rare pediatric diseases, qualitative studies have shown that Facebook online support groups are utilized by and beneficial for persons affected by rare pediatric diseases. Nonetheless, the extent of this usage has not been investigated.ObjectiveThis study aims to provide a comprehensive quantitative analysis of the extent of Facebook usage as a tool for rare pediatric disease support groups and to explore factors that influence a disease's representation on Facebook. These results potentially offer important insights for future public health initiatives and give direction to further research that can give much needed support to parents of children with rare diseases.MethodsWe determined rare pediatric diseases using the inventory of the online portal Orphanet. Facebook support groups were identified by searching 5 synonymous disease descriptions using the group category search bar. Disease- and group-describing parameters were statistically analyzed using standard descriptive statistical methods.Results6398 Facebook support groups, representing 826 diseases (19.5% of all searched diseases), were found. 69% are private groups. Group type, size, activity (sum of posts, comments, and reactions calculated by Facebook), new memberships, and language varied largely between groups (member count: minimum 1, maximum 23,414; activity last 30 days: minimum 0, maximum 3606). The highest percentage of awareness and information groups was found for teratogenic diseases (18/68, 26%). The odds of finding a Facebook group increased according to the level of information available about the disease: known prevalence (odds ratio [OR] 3.98, 95% CI 3.39-4.66, P<.001), known disease type (OR 3.15, 95% CI 2.70-3.68, P<.001), and known inheritance mode (OR 2.06, 95% CI 1.68-2.52, P<.001) were all associated with higher odds of finding a Facebook group, as was dominant compared to nondominant inheritance (OR 2.05, 95% CI 1.74-3.42, P<.001). The number of groups per disease increased with higher prevalence.ConclusionsFacebook is widely used as a tool for support groups for rare pediatric diseases and continues to be relevant. Two-thirds of the groups are private groups, indicating group participants' need for privacy, which should be further explored. The advantages and limitations of Facebook as a tool for support groups in the field of rare diseases should be further investigated as it will allow health professionals to use Facebook more meaningfully in their counseling and guidance of affected individuals and their family members.

Dataset Information

GeneVetter: a web tool for quantitative monogenic assessment of rare diseases.

Unlabelled

Availability and implementation

Contact

Supplementary information

Publications

GeneVetter: a web tool for quantitative monogenic assessment of rare diseases.

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