Long read whole genome sequencing-based discovery of complex structural variants and their role in aetiology of non-syndromic autism spectrum disorder in India DOI Creative Commons

Jhanvi Shah,

Dinesh Mondal, Deepika Jain

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Background: Despite having heritability estimates of 80%, approximately 50% cases autism spectrum disorders (ASD) remain without a genetic diagnosis. Complex structural variants (SVs) detected using long-read genome sequencing are relatively new class implicated in neurodevelopmental disorders. Short read (SRS) and chromosomal microarray (CMA) unable to resolve these SVs due their inherent technological limitations. This study was aimed detect delineate the role children with non-syndromic ASDs long whole (lrWGS) whom prior traditional tests did not yield definitive Methods: A total 23 patients no diagnosis from karyotyping, Fragile-X analysis, CMA short exome (srWES) were selected for lrWGS Oxford Nanopore based platform. All samples sequenced at an average coverage ~10x. Contigs generated high accuracy base calling aligned against GRCh38/hg38 human reference build. called five variant callers- Sniffles2, cuteSV, NanoVar SVIM npInv, annotated AnnotSV. Concordant calls across least three callers filtered prioritized downstream analysis. Candidate validated by orthogonal methods. Results: A 46 low pass runs performed (two runs/ sample). The N50 length 6.74±3.31 kb obtained runs, on average, 176,432 made all each sample. number deletions, duplications, insertions, inversions translocations 47,375, 2,498, 62,657, 1084 62,817, respectively per Of cases, candidate SV, inversion 2.7 Mb size encompassing SNAP25-AS1 gene observed. This is likely be involved synaptic pathway has previously been associated autism. Conclusion: first India assess complex aetiology ASDs. Despite small sample size, results suggest limited ASD. Dearth data supporting other cohorts around world further supports our conclusion. Hence, inclusion clinical ASD currently supported.

Язык: Английский

Long read whole genome sequencing-based discovery of complex structural variants and their role in aetiology of non-syndromic autism spectrum disorder in India DOI Creative Commons

Jhanvi Shah,

Dinesh Mondal, Deepika Jain

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Background: Despite having heritability estimates of 80%, approximately 50% cases autism spectrum disorders (ASD) remain without a genetic diagnosis. Complex structural variants (SVs) detected using long-read genome sequencing are relatively new class implicated in neurodevelopmental disorders. Short read (SRS) and chromosomal microarray (CMA) unable to resolve these SVs due their inherent technological limitations. This study was aimed detect delineate the role children with non-syndromic ASDs long whole (lrWGS) whom prior traditional tests did not yield definitive Methods: A total 23 patients no diagnosis from karyotyping, Fragile-X analysis, CMA short exome (srWES) were selected for lrWGS Oxford Nanopore based platform. All samples sequenced at an average coverage ~10x. Contigs generated high accuracy base calling aligned against GRCh38/hg38 human reference build. called five variant callers- Sniffles2, cuteSV, NanoVar SVIM npInv, annotated AnnotSV. Concordant calls across least three callers filtered prioritized downstream analysis. Candidate validated by orthogonal methods. Results: A 46 low pass runs performed (two runs/ sample). The N50 length 6.74±3.31 kb obtained runs, on average, 176,432 made all each sample. number deletions, duplications, insertions, inversions translocations 47,375, 2,498, 62,657, 1084 62,817, respectively per Of cases, candidate SV, inversion 2.7 Mb size encompassing SNAP25-AS1 gene observed. This is likely be involved synaptic pathway has previously been associated autism. Conclusion: first India assess complex aetiology ASDs. Despite small sample size, results suggest limited ASD. Dearth data supporting other cohorts around world further supports our conclusion. Hence, inclusion clinical ASD currently supported.

Язык: Английский

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