scholarly journals RDmap: A Map for Exploring Rare Diseases

2021 ◽  
Author(s):  
Jian Yang ◽  
Cong Dong ◽  
Huilong Duan ◽  
Qiang Shu ◽  
Haomin Li
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Distance Matrix ◽  
Disease Diagnosis ◽  
Human Phenotype ◽  
Pathogenic Genes ◽  
Disease Information ◽  
Rare Genetic Diseases ◽  
Interactive Map

Abstract Background: The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases makes the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods: A distance matrix of rare diseases included in Orphanet was measured by calculating the quantitative distance among phenotypes and pathogenic genes based on Human Phenotype Ontology (HPO) and Gene Ontology (GO), and each disease was mapped into Euclidean space. A rare disease map, enhanced by clustering classes and disease information, was developed based on ECharts. Results: A rare disease map called RDmap was published at http://rdmap.nbscn.org. Total 3,287 rare diseases are included in the phenotype-based map, and 3,789 rare genetic diseases are included in the gene-based map; 1,718 overlapping diseases are connected between two maps. RDmap works similarly to the widely used Google Map service and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword searches in an in silico evaluation, and 20 published cases of rare diseases also demonstrated that RDmap can assist clinicians in seeking the rare disease diagnosis. Conclusion: RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasingly complicated realm of rare genetic diseases.

scholarly journals RDmap: a map for exploring rare diseases

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jian Yang ◽  
Cong Dong ◽  
Huilong Duan ◽  
Qiang Shu ◽  
Haomin Li
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Distance Matrix ◽  
Disease Diagnosis ◽  
Human Phenotype ◽  
Pathogenic Genes ◽  
Disease Information ◽  
Rare Genetic Diseases ◽  
Interactive Map

Abstract Background The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases makes the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods A distance matrix of rare diseases included in Orphanet was measured by calculating the quantitative distance among phenotypes and pathogenic genes based on Human Phenotype Ontology (HPO) and Gene Ontology (GO), and each disease was mapped into Euclidean space. A rare disease map, enhanced by clustering classes and disease information, was developed based on ECharts. Results A rare disease map called RDmap was published at http://rdmap.nbscn.org. Total 3287 rare diseases are included in the phenotype-based map, and 3789 rare genetic diseases are included in the gene-based map; 1718 overlapping diseases are connected between two maps. RDmap works similarly to the widely used Google Map service and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword searches in an in silico evaluation, and 20 published cases of rare diseases also demonstrated that RDmap can assist clinicians in seeking the rare disease diagnosis. Conclusion RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasingly complicated realm of rare genetic diseases.

scholarly journals RDmap: A Map for Exploring Rare Diseases

2020 ◽  
Author(s):  
Jian Yang ◽  
Cong Dong ◽  
Huilong Duan ◽  
Qiang Shu ◽  
Haomin Li
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Keyword Search ◽  
Genetic Diseases ◽  
Distance Matrix ◽  
Pathogenic Genes ◽  
Disease Information ◽  
Rare Genetic Diseases ◽  
Interactive Map ◽  
Location Function

Abstract Background: The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases make the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods: By defining the quantitative distance among phenotypes and pathogenic genes based on corresponding ontology systems, the distance matrix of rare diseases included in Orphanet was calculated and mapped into Euclidean space. Enhanced by clustering classes and disease information, a rare disease map was developed based on ECharts. Results: The rare disease map called RDmap was published at http://rdmap.nbscn.org. The phenotype-based map comprises 3,287 rare diseases and the gene-based map comprises 3,789 rare genetic diseases and they were bridged by 1,718 overlapping diseases. RDmap works similar to the widely used Google map and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword search in an in-silico evaluation and 20 published cases of rare diseases also demonstrated that RDmap can be used by clinicians to improve diagnosis. Conclusion: RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasing complicated rare genetic diseases.

scholarly journals Barriers and Considerations for Diagnosing Rare Diseases in Indigenous Populations

2020 ◽  
Vol 8 ◽  
Author(s):  
Carla S. D'Angelo ◽  
Azure Hermes ◽  
Christopher R. McMaster ◽  
Elissa Prichep ◽  
Étienne Richer ◽  
...  
Keyword(s):  
Rare Disease ◽  
Genetic Diseases ◽  
Disease Diagnosis ◽  
Indigenous Populations ◽  
Genomic Research ◽  
Medical Attention ◽  
Genomic Technologies ◽  
Rare Genetic Diseases ◽  
Research Consortium ◽  
Multi Stakeholder

Advances in omics and specifically genomic technologies are increasingly transforming rare disease diagnosis. However, the benefits of these advances are disproportionately experienced within and between populations, with Indigenous populations frequently experiencing diagnostic and therapeutic inequities. The International Rare Disease Research Consortium (IRDiRC) multi-stakeholder partnership has been advancing toward the vision of all people living with a rare disease receiving an accurate diagnosis, care, and available therapy within 1 year of coming to medical attention. In order to further progress toward this vision, IRDiRC has created a taskforce to explore the access barriers to diagnosis of rare genetic diseases faced by Indigenous peoples, with a view of developing recommendations to overcome them. Herein, we provide an overview of the state of play of current barriers and considerations identified by the taskforce, to further stimulate awareness of these issues and the passage toward solutions. We focus on analyzing barriers to accessing genetic services, participating in genomic research, and other aspects such as concerns about data sharing, the handling of biospecimens, and the importance of capacity building.

scholarly journals Genomics of rare genetic diseases—experiences from India

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Sridhar Sivasubbu ◽  
◽  
Vinod Scaria
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Collaborative Research ◽  
Disease Burden ◽  
Genetic Diseases ◽  
Community Services ◽  
Health Concern ◽  
Healthy Population ◽  
Rare Genetic Diseases ◽  
Research Initiative

Abstract Home to a culturally heterogeneous population, India is also a melting pot of genetic diversity. The population architecture characterized by multiple endogamous groups with specific marriage patterns, including the widely prevalent practice of consanguinity, not only makes the Indian population distinct from rest of the world but also provides a unique advantage and niche to understand genetic diseases. Centuries of genetic isolation of population groups have amplified the founder effects, contributing to high prevalence of recessive alleles, which translates into genetic diseases, including rare genetic diseases in India. Rare genetic diseases are becoming a public health concern in India because a large population size of close to a billion people would essentially translate to a huge disease burden for even the rarest of the rare diseases. Genomics-based approaches have been demonstrated to accelerate the diagnosis of rare genetic diseases and reduce the socio-economic burden. The Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN) stands for providing genomic solutions for rare diseases in India. The consortium aims to establish a unique collaborative framework in health care planning, implementation, and delivery in the specific area of rare genetic diseases. It is a nation-wide collaborative research initiative catering to rare diseases across multiple cohorts, with over 240 clinician/scientist collaborators across 70 major medical/research centers. Within the GUaRDIAN framework, clinicians refer rare disease patients, generate whole genome or exome datasets followed by computational analysis of the data for identifying the causal pathogenic variations. The outcomes of GUaRDIAN are being translated as community services through a suitable platform providing low-cost diagnostic assays in India. In addition to GUaRDIAN, several genomic investigations for diseased and healthy population are being undertaken in the country to solve the rare disease dilemma. In summary, rare diseases contribute to a significant disease burden in India. Genomics-based solutions can enable accelerated diagnosis and management of rare diseases. We discuss how a collaborative research initiative such as GUaRDIAN can provide a nation-wide framework to cater to the rare disease community of India.

Cooccurrence of Two Different Genetic Diseases: A Case of Valproic Acid Hepatotoxicity in Nicolaides–Baraitser Syndrome (SMARCA2 Mutation)—Due to a POLG1-Related Effect?

2019 ◽  
Vol 51 (01) ◽  
pp. 049-052
Author(s):  
Benedikt Hofmeister ◽  
Celina von Stülpnagel ◽  
Steffen Berweck ◽  
Angela Abicht ◽  
Gerhard Kluger ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Literature Review ◽  
Rare Disease ◽  
Clinical Features ◽  
Rare Diseases ◽  
Rare Complication ◽  
Genetic Diseases ◽  
Related Effect ◽  
Higher Sensitivity ◽  
Polg1 Mutation

AbstractNicolaides–Baraitser syndrome (NCBRS) is a rare disease caused by a mutation in the SMARCA2 gene. Clinical features include craniofacial dysmorphia and abnormalities of the limbs, as well as intellectual disorder and often epilepsy. Hepatotoxicity is a rare complication of the therapy with valproic acid (VPA) and a mutation of the polymerase γ (POLG) might lead to a higher sensitivity for liver hepatotoxicity. We present a patient with the coincidence of two rare diseases, the NCBRS and additionally a POLG1 mutation in combination with a liver hepatotoxicity. The co-occurrence in children for two different genetic diseases is discussed with the help of literature review.

Ethics and equity in rare disease research and healthcare

2021 ◽  
Author(s):  
Maria Koromina ◽  
Vasileios Fanaras ◽  
Gareth Baynam ◽  
Christina Mitropoulou ◽  
George P Patrinos
Keyword(s):  
Rare Diseases ◽  
Ethical Issues ◽  
Genetic Diseases ◽  
Ethical Framework ◽  
Middle Income ◽  
Next Generation Sequencing Technology ◽  
Ethical Frameworks ◽  
Rare Genetic Diseases ◽  
Conducting Research ◽  
Key Aspects

Rapid advances in next-generation sequencing technology, particularly whole exome sequencing and whole genome sequencing, have greatly affected our understanding of genetic variation underlying rare genetic diseases. Herein, we describe ethical principles of guiding consent and sharing of genomics research data. We also discuss ethical dilemmas in rare diseases research and patient recruitment policies and address bioethical and societal aspects influencing the ethical framework for genetic testing. Moreover, we focus on addressing ethical issues surrounding research in low- and middle-income countries. Overall, this perspective aims to address key aspects and issues for building proper ethical frameworks, when conducting research involving genomics data with a particular emphasis on rare diseases and genetics testing.

scholarly journals Research and Management of Rare Diseases in the COVID-19 Pandemic Era: Challenges and Countermeasures

2021 ◽  
Vol 9 ◽  
Author(s):  
Sanjana Fatema Chowdhury ◽  
Syed Muktadir Al Sium ◽  
Saeed Anwar
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Management Strategies ◽  
Routine Care ◽  
Ongoing Research ◽  
The People ◽  
Number Of Patients ◽  
High Level ◽  
Disease Community

The ongoing coronavirus disease 2019 (COVID-19) pandemic has disrupted every aspect of our life. The need to provide high-level care for an enormous number of patients with COVID-19 infection during this pandemic has impacted resourcing for and restricted the routine care of all non-COVID-19 conditions. Since the beginning of the pandemic, the people living with rare disorders, who represent a marginalized group of the population even in a normal world, have not received enough attention that they deserve. Due to the pandemic situation, they have experienced (and experiencing) an extreme inadequacy of regular clinical services, counseling, and therapies they need, which have made their life more vulnerable and feel more marginalized. Besides, the clinicians, researchers, and scientists working on rare genetic diseases face extra challenges due to the pandemic. Many ongoing research projects and clinical trials for rare and genetic diseases were stalled to avoid patients' and research staff's transmission to COVID-19. Still, with all the odds, telehealth and virtual consultations for rare disease patients have shown hope. The clinical, organizational, and economic challenges faced by institutions, patients, their families, and the caregivers during the pandemic indicate the importance of ensuring continuity of care in managing rare diseases, including adequate diagnostics and priority management strategies for emergencies. In this review, we endeavored to shed light on the issues the rare disease community faces during the pandemic and the adaptations that could help the rare disease community to better sustain in the coming days.

The Importance of Hematology Working Groups for Rare Genetic Diseases

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Marwan Elbagoury ◽  
Ohoud F. Kashari
Keyword(s):  
Rare Disease ◽  
Genetic Diseases ◽  
Correct Diagnosis ◽  
Coordination Of Care ◽  
Gulf Region ◽  
Diagnostic Odyssey ◽  
Whole Exome ◽  
Rare Genetic Diseases ◽  
Working Groups

Rationale Around the globe, it is now understood that individuals with Rare genetic Diseases routinely face limitations to getting access to diagnosis. Plans have been created to improve the requirements of the patient's communities, including access to multidisciplinary care, and proposing new corrections or amendments to existing strategies. In the gulf region, numerous proposals have been established to tackle the diagnosis and management Rare genetic Diseases. Introduction and Background Rare genetic diseases are characterized as life-long, serious conditions that debilitate or compromise life. Almost 80% of Rare genetic diseases are diagnosed during the childhood. Absence of access to these assets affect patients and their families living with complex needs that may incorporate day in and day out observing, continuous serious physical and formative medicines, remaining in the training framework, and now and then costly strength meds1. The underlying etiology may stay obscure for many patients with rare genetic diseases despite multiple investigations. patients may be assigned an incorrect diagnosis and be referred to several specialties until a correct diagnosis can be made. A correct diagnosis of rare genetic diseases may impact not only the patient's care but may have further implications for management and/or counselling of family members as well2. Also, Early diagnosis leading to early treatment to prevent long-term damage. Global Landscape3 Rarity of diseases is most commonly defined based on prevalence and incidence within a jurisdiction, or in some cases by a combination of factors based on severity and the existence or feasibility of alternative therapeutic options. Globally, the following areas of focus aimed at improving the delivery of health care for the rare disease population: - Improve access to early diagnosis, timely intervention, coordinated care for rare genetic disease patients and developing referral pathways for rare genetic disease patients to facilitate efficient care deliver - Provide educational resources and knowledge exchange opportunities to health professionals to allow them to better identify, manage and treat rare disea - support integrated peer networks, patient organizations to ensure that rare disease patients, their family/caregivers and support them to make informed decisions about their condition. The importance of having working groups for Rare genetic Diseases in Gulf region 4 - Encourage improved coordination of care and access to particular information for rare genetic diseaseses. - Create a complete system services suppliers over Gulf states. Assets and Gaps analysis 1- Early Detection and Diagnostics 5 There are resources that assist the diagnostic capacity and early detection for rare genetic diseases. · Whole Exome sequencing are used mainly for research purposes, despite the fact that their use will reduced diagnostic odyssey. · Lack of the availability of testing is dependent on budget support in some hospitals. - Timely Access to Evidence-based care 6 - Family doctors may not be well equipped to meet the needs of patients with rare hematological genetic diseases, even after diagnosis. - Poor access supportive services for adult care. - Access to genetic counseling for patients and families outside major academic hospitals7. References 1. Sawyer, S. L. et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin. Genet.89, 275-284 (2016). 2. Undiagnosed Diseases Network Manual of Operations. (2018). 3. Richter, T. et al. Rare Disease Terminology and Definitions-A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group. (2015). doi:10.1016/j.jval.2015.05.008 4. International Rare Disease Research Consortium& GUIDELINES Long version. (2013). 5. Clinical Handbook for Sickle Cell Disease Vaso-occlusive Crisis Provincial Council for Maternal and Child Health & Ministry of Health and Long-Term Care. (2017). 6. Therrell, B. L. et al. Current status of newborn screening worldwide: 2015. Seminars in Perinatology39, 171-187 (2015). 7. Stille, C. J. & Antonelli, R. C. Coordination of care for children with special health care needs. Current Opinion in Pediatrics16, 700-705 (2004). Figure Disclosures No relevant conflicts of interest to declare.

GeneBreaker - Variant simulation to improve the diagnosis of Mendelian rare genetic diseases

2020 ◽  
Author(s):  
Phillip A. Richmond ◽  
Tamar V. Av-Shalom ◽  
Oriol Fornes ◽  
Bhavi Modi ◽  
Alison M. Elliott ◽  
...  
Keyword(s):  
Rare Disease ◽  
Genetic Diseases ◽  
Genomic Medicine ◽  
Real Life ◽  
Variant Calling ◽  
Pathogenic Variants ◽  
Rare Genetic Diseases ◽  
Diagnosis Rate ◽  
Effective Use ◽  
Potential Pathogenicity

AbstractMendelian rare genetic diseases affect 5-10% of the population, and with over 5,300 genes responsible for ~7,000 different diseases, they are challenging to diagnose. The use of whole genome sequencing (WGS) has bolstered the diagnosis rate significantly. Effective use of WGS relies upon the ability to identify the disrupted gene responsible for disease phenotypes. This process involves genomic variant calling and prioritization, and is the beneficiary of improvements to sequencing technology, variant calling approaches, and increased capacity to prioritize genomic variants with potential pathogenicity. As analysis pipelines continue to improve, careful testing of their efficacy is paramount. However, real-life cases typically emerge anecdotally, and utilization of clinically sensitive and identifiable data for testing pipeline improvements is regulated and limiting. We identified the need for a gene-based variant simulation framework which can create mock rare disease scenarios, utilizing known pathogenic variants or through the creation of novel gene-disrupting variants. To fill this need, we present GeneBreaker, a tool which creates synthetic rare disease cases with utility for benchmarking variant calling approaches, testing the efficacy of variant prioritization, and as an educational mechanism for training diagnostic practitioners in the expanding field of genomic medicine. GeneBreaker is freely available at http://GeneBreaker.cmmt.ubc.ca.

scholarly journals Reference exome data for a Northern Brazilian population

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Alexia L. Weeks ◽  
Richard W. Francis ◽  
Joao I. C. F. Neri ◽  
Nathaly M. C. Costa ◽  
Nivea M. R. Arrais ◽  
...  
Keyword(s):  
Rare Diseases ◽  
Sequence Data ◽  
Genetic Diseases ◽  
Specific Reference ◽  
Single Nucleotide Variants ◽  
Data Set ◽  
Single Nucleotide ◽  
Rare Genetic Diseases ◽  
Genetics And Genomics ◽  
Brazilian Cohort

Abstract Exome sequencing is widely used in the diagnosis of rare genetic diseases and provides useful variant data for analysis of complex diseases. There is not always adequate population-specific reference data to assist in assigning a diagnostic variant to a specific clinical condition. Here we provide a catalogue of variants called after sequencing the exomes of 45 babies from Rio Grande do Nord in Brazil. Sequence data were processed using an ‘intersect-then-combine’ (ITC) approach, using GATK and SAMtools to call variants. A total of 612,761 variants were identified in at least one individual in this Brazilian Cohort, including 559,448 single nucleotide variants (SNVs) and 53,313 insertion/deletions. Of these, 58,111 overlapped with nonsynonymous (nsSNVs) or splice site (ssSNVs) SNVs in dbNSFP. As an aid to clinical diagnosis of rare diseases, we used the American College of Medicine Genetics and Genomics (ACMG) guidelines to assign pathogenic/likely pathogenic status to 185 (0.32%) of the 58,111 nsSNVs and ssSNVs. Our data set provides a useful reference point for diagnosis of rare diseases in Brazil. (169 words).

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