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View article: Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption
Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption Open
The major spliceosome contains five small nuclear RNAs (snRNAs; U1, U2, U4, U5 and U6) essential for splicing. Variants in RNU4-2, encoding U4, cause a neurodevelopmental disorder called ReNU syndrome. We investigated de novo variants in 5…
View article: A Mosaic Hotspot <scp><i>PLCD1</i></scp> Variant, Detectable in Blood‐Derived <scp>DNA</scp>, Associated With Nevus Trichilemmocysticus
A Mosaic Hotspot <span><i>PLCD1</i></span> Variant, Detectable in Blood‐Derived <span>DNA</span>, Associated With Nevus Trichilemmocysticus Open
View article: One-Sided Matching Portal (OSMP): A Tool to Facilitate Rare Disease Patient Matchmaking.
One-Sided Matching Portal (OSMP): A Tool to Facilitate Rare Disease Patient Matchmaking. Open
As demonstrated through the two pilot studies, one-sided matchmaking queries can be efficiently performed using the OSMP. The availability of variant-level and participant-level data is key to ensuring this approach is practical for resear…
View article: Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon
Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon Open
View article: A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus
A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus Open
View article: Leveraging cancer mutation data to predict the pathogenicity of germline missense variants
Leveraging cancer mutation data to predict the pathogenicity of germline missense variants Open
Innovative and easy-to-implement strategies are needed to improve the pathogenicity assessment of rare germline missense variants. Somatic cancer driver mutations identified through large-scale tumor sequencing studies often impact genes t…
View article: Table of Contents, Volume 194A, Number 3, March 2024
Table of Contents, Volume 194A, Number 3, March 2024 Open
View article: O36: Long-read genome sequencing in unsolved rare genetic diseases: Preliminary experiences from the Care4Rare Canada Consortium
O36: Long-read genome sequencing in unsolved rare genetic diseases: Preliminary experiences from the Care4Rare Canada Consortium Open
Short read genome sequencing (sr-GS) is a powerful tool but is limited in detection of larger genomic changes and in non-unique regions of the genome. With greatly increased read lengths, long-read genome sequencing (lr-GS) provides accura…
View article: P605: RNA sequencing as a second-line test for rare disease
P605: RNA sequencing as a second-line test for rare disease Open
The clinical implementation of next-generation sequencing has revolutionized genetic diagnostics of rare disease, yet many exome and genome analyses remain inconclusive. This is due in part to challenges with variant detection, prioritizat…
View article: Biallelic <i>SOX8</i> Variants Associated With Novel Syndrome With Myopathy, Skeletal Deformities, Intellectual Disability, and Ovarian Dysfunction
Biallelic <i>SOX8</i> Variants Associated With Novel Syndrome With Myopathy, Skeletal Deformities, Intellectual Disability, and Ovarian Dysfunction Open
Our findings associate SOX8 variants with this novel condition, highlight how complex genome regulation can complicate novel disease-gene identification, and provide insight into the molecular pathogenesis of this disease.
View article: A common flanking variant is associated with enhanced meiotic stability of the<i>FGF14</i>-SCA27B locus
A common flanking variant is associated with enhanced meiotic stability of the<i>FGF14</i>-SCA27B locus Open
The factors driving initiation of pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14 -SCA27B (GAA)•(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a 5’-fla…
View article: P509: Resolution of variants of uncertain significance by RNA sequencing
P509: Resolution of variants of uncertain significance by RNA sequencing Open
View article: Genomics4RD: An integrated platform to share Canadian deep-phenotype and multiomic data for international rare disease gene discovery.
Genomics4RD: An integrated platform to share Canadian deep-phenotype and multiomic data for international rare disease gene discovery. Open
Despite recent progress in the understanding of the genetic etiologies of rare diseases (RDs), a significant number remain intractable to diagnostic and discovery efforts. Broad data collection and sharing of information among RD researche…
View article: Genome-wide sequencing and the clinical diagnosis of genetic disease: The CAUSES study
Genome-wide sequencing and the clinical diagnosis of genetic disease: The CAUSES study Open
View article: Author response: KDM5A mutations identified in autism spectrum disorder using forward genetics
Author response: KDM5A mutations identified in autism spectrum disorder using forward genetics Open
View article: XYalign: Version 1.1.6
XYalign: Version 1.1.6 Open
The high degree of similarity between gametologous sequences on the sex chromosomes can lead to the misalignment of sequencing reads and substantially affect variant calling. Here we present XYalign, a new tool that (1) quickly infers sex …
View article: Identifying, understanding, and correcting technical biases on the sex chromosomes in next-generation sequencing data
Identifying, understanding, and correcting technical biases on the sex chromosomes in next-generation sequencing data Open
Mammalian X and Y chromosomes share a common evolutionary origin and retain regions of high sequence similarity. This sequence homology can cause the mismapping of short sequencing reads derived from the sex chromosomes and affect variant …
View article: Additional file 6: Table S4. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
Additional file 6: Table S4. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Open
Detailed variant information for all verified variants, including ACMG classification â Table showing details for variant classification such as pathogenicity prediction algorithms results and details of ACMG criteria application. (XLSX 18…
View article: A bioinformatic workflow for analyzing whole genomes in rare Mendelian disease
A bioinformatic workflow for analyzing whole genomes in rare Mendelian disease Open
The vast majority of the human genome (~98%) is non-coding. A symphony of non-coding sequences resides in the genome, interacting with genes and the environment to tune gene expression. Functional non-coding sequences include enhancers, si…
View article: Additional file 8: Table S6. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
Additional file 8: Table S6. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Open
Raw data for SNVs detected across all patients by Mendelian Inheritance Pattern filtering â all SNVs detected per trio, organized as one trio per sheet, using the Mendelian inheritance filtering. Sheet 1 gives the legend. All SNVs are anno…
View article: Additional file 4: Table S3. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
Additional file 4: Table S3. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Open
UK10K study cohorts that comprise the positive control cohort â Table giving descriptions of the study cohorts from the UK10K project that comprised the positive control cohorts and conditions for use. (XLSX 13 kb)
View article: Additional file 7: Table S5. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
Additional file 7: Table S5. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Open
Significantly enriched KEGG pathways for PDS burden in positive control cohort â Details for pathway enrichment analysis showing all KEGG pathways and burden of enrichment for each in the positive control cohort. (XLSX 15 kb)
View article: Additional file 10: Table S8. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
Additional file 10: Table S8. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Open
Summary of SNVs and CNVs across 8 ID patients in DVPRR â Details on all SNVS and CNVs detected in DVPRR for all patients, organized by those intersecting with DDD genes and those with UPP genes. (XLSX 40 kb)
View article: Additional file 3: Table S2. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
Additional file 3: Table S2. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Open
Primers for verification - All primer sequences used for SNV, CNV and SV verification. (XLSX 18 kb)
View article: Additional file 2: Table S1. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
Additional file 2: Table S1. of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Open
Test of relatedness - Table showing relatedness for each trio by comparing SNP concordance between child, mother and father. (XLSX 17 kb)
View article: Additional file 9: Table S7 of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
Additional file 9: Table S7 of Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Open
CNV/SV/Indel Verification Summary â Table giving a list of all indels, CNVs and SVs (inversions and translocations), and details on their verification. (XLSX 15 kb)
View article: XYalign: Inferring and Correcting for Sex Chromosome Ploidy in Next-Generation Sequencing Data
XYalign: Inferring and Correcting for Sex Chromosome Ploidy in Next-Generation Sequencing Data Open
Sex chromosome aneuploidies are currently estimated to be as common as 1/400 in humans. Atypical ploidy will affect variant calling and measures of genomic variation that are central to most clinical genomic studies. Further, the high degr…