Skip to main content

Rare disease gene

Rare disease gene association discovery in the 100,000 Genomes Project


Up to 80% of rare disease patients remain undiagnosed after genomic sequencing1, with many probably involving pathogenic variants in yet to be discovered disease–gene associations. To search for such associations, we developed a rare variant gene burden analytical framework for Mendelian diseases, and applied it to protein-coding variants from whole-genome sequencing of 34,851 cases and their family members recruited to the 100,000 Genomes Project2. A total of 141 new associations were identified, including five for which independent disease–gene evidence was recently published. Following in silico triaging and clinical expert review, 69 associations were prioritized, of which 30 could be linked to existing experimental evidence.

The five associations with strongest overall genetic and experimental evidence were monogenic diabetes with the known β cell regulator3,4 UNC13A, schizophrenia with GPR17, epilepsy with RBFOX3, Charcot–Marie–Tooth disease with ARPC3 and anterior segment ocular abnormalities with POMK. Further confirmation of these and other associations could lead to numerous diagnoses, highlighting the clinical impact of large-scale statistical approaches to rare disease–gene association discovery.

Rare diseases collectively affect 3.5% to 5.9% of people worldwide5. Despite advances in genomic sequencing, molecular diagnosis continues to elude 50% to 80% of patients presenting to genetic clinics1. Furthermore, fewer than half of the 10,000 rare Mendelian diseases in the Online Mendelian Inheritance in Man (OMIM) database6 have an established genetic basis. Diagnostic failure may arise because of a lack of routine screening for non-coding7 or structural variants1. However, it is likely that a substantial proportion of the pathogenic variants responsible for patients undiagnosed with rare disease (cases) reside in those yet to be discovered genes associated with (possibly very rare) disorders.

The scale of rare disease sequencing studies, such as the Undiagnosed Disease Network8, Centers for Mendelian Genomics9, Deciphering Developmental Disorders10 and the 100,000 Genomes Project (100KGP)2, offers expanded opportunities to provide insight into pathogenic mechanisms of inherited disease, including the possibility of establishing disease–gene associations through case–control analyses, akin to methods used previously to identify common genetic variants influencing the risk of complex disorders. Such an approach provides much-needed power to identify genes harbouring rare pathogenic variants.

genetics awards, genomics, DNA research, hereditary science, gene editing, CRISPR recognition, genetic breakthroughs, medical genetics, population genetics, biotechnology awards, Nobel Prize in Genetics, genomic medicine, genetic innovation, molecular biology, personalized medicine, genetics research grants, bioinformatics, evolutionary genetics, genetic engineering, scientific excellence

#GeneticsAwards #Genomics #DNAResearch #HereditaryScience #GeneEditing #CRISPRRecognition #GeneticBreakthroughs #MedicalGenetics #PopulationGenetics #BiotechAwards #NobelPrizeGenetics #GenomicMedicine #GeneticInnovation #MolecularBiology #PersonalizedMedicine #GeneticsResearch #Bioinformatics #EvolutionaryGenetics #GeneticEngineering #ScientificExcellence

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

Comments

Post a Comment

Popular posts from this blog

Chromosomal Abnormalities

  Chromosomal Abnormalities Chromosome abnormalities refer to structural or numerical changes in chromosomes that can disrupt normal genetic function, leading to developmental disorders, congenital abnormalities, and various genetic diseases. These abnormalities may arise from errors in cell division, such as nondisjunction or chromosomal breakage, resulting in conditions like Down syndrome , Turner syndrome, Klinefelter syndrome , and various deletion or duplication syndromes. Understanding chromosome abnormalities is essential for genetic counseling, prenatal diagnosis, disease risk assessment, and research in cytogenetics and molecular genetics. Chromosome abnormalities, chromosomal disorders, chromosomal mutations, aneuploidy, structural chromosome abnormalities, nondisjunction, deletion syndrome, duplication syndrome , translocation, inversion, cytogenetics, karyotyping, prenatal diagnosis , genetic testing, genomic instability, Down syndrome, Turner syndrome, Klinefelter syn...
Post a Comment
Read more

Multifactorial Genetic Conditions

Multifactorial Genetic Conditions Multifactorial genetic conditions are disorders caused by the combined effects of multiple genes and environmental factors , rather than a single gene mutation . These conditions do not follow classic Mendelian inheritance patterns and instead result from complex gene–environment interactions . Factors such as lifestyle, nutrition, infections, stress, and exposure to toxins can significantly influence disease onset and severity in genetically susceptible individuals. Common examples include diabetes, cardiovascular diseases , neural tube defects, asthma, and many neuropsychiatric disorders. Understanding multifactorial inheritance is essential for risk prediction, preventive medicine, and personalized healthcare strategies. Multifactorial inheritance, polygenic traits, gene–environment interaction, complex diseases, genetic susceptibility, environmental risk factors, non-Mendelian inheritance, disease predisposition, polygenic risk score, precision ...
Post a Comment
Read more

Human Brain Organoids

Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation The developing human foetal brain is sensitive to thermal stimulation during pregnancy. However, the mechanisms by which heat exposure affects human foetal brain development remain unclear, largely due to the lack of appropriate research models for studying thermal stimulation. To address this, we have developed a periodic heating model based on brain organoids derived from human pluripotent stem cells. The model recapitulated neurodevelopmental disruptions under prenatal heat exposure at the early stages, providing a paradigm for studying the altered neurodevelopment under environmental stimulation. Our study found that periodic heat exposure led to decreased size and impaired neural tube development in the brain organoids. Bulk RNA-seq analysis revealed that the abnormal WNT signalling pathway and the reduction of G2/M progenitor cells might be involved in heat stimulation. Further investi...
Post a Comment
Read more