Publications by authors named "Ian J McLaughlin"

Article Synopsis
  • The Genome in a Bottle Consortium (GIAB) is creating matched tumor-normal samples that are publicly consented for sharing genomic data and cell lines, focusing on pancreatic ductal adenocarcinoma (PDAC).
  • They provide a comprehensive genomic dataset from the first individual, combining high-depth DNA from tumor and normal cells using advanced whole genome sequencing technologies.
  • This open-access resource aims to help develop benchmarks for detecting genetic variants in cancer, fostering innovation in genome measurement and analysis tools.
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Resolving the molecular basis of a Mendelian condition (MC) remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome, and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion, and structural variant calling and diploid genome assembly, and permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility, and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network (UDN) participant with a chromosome X;13 balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes (, , , and ) previously associated with single-gene MCs.

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  • A study utilized No-Amp sequencing to analyze hexanucleotide expansions in the C9orf72 gene, a leading genetic cause of certain neurodegenerative diseases, by examining cerebellar tissue from 28 patients.
  • The research found a strong correlation between expansion sizes measured by No-Amp sequencing and traditional Southern blotting methods, indicating the effectiveness of this new sequencing technique.
  • Results revealed that smaller C9orf72 expansions were associated with increased survival rates and higher levels of specific transcripts and proteins, with a high GC content observed in the repeat expansions, emphasizing the significance of the expansion size in C9orf72-related disorders.
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Amplification of a CAG trinucleotide motif (CTG18.1) within the TCF4 gene has been strongly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Nevertheless, a small minority of clinically unaffected elderly patients who have expanded CTG18.

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Background: Many neurodegenerative diseases are caused by nucleotide repeat expansions, but most expansions, like the C9orf72 'GGGGCC' (GC) repeat that causes approximately 5-7% of all amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases, are too long to sequence using short-read sequencing technologies. It is unclear whether long-read sequencing technologies can traverse these long, challenging repeat expansions. Here, we demonstrate that two long-read sequencing technologies, Pacific Biosciences' (PacBio) and Oxford Nanopore Technologies' (ONT), can sequence through disease-causing repeats cloned into plasmids, including the FTD/ALS-causing GC repeat expansion.

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