Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion.

Background: The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods: We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method.

Single cell multiomics reveal divergent effects of DNMT3A and TET2 mutant clonal hematopoiesis in inflammatory response.

DNMT3A and TET2 are epigenetic regulator genes commonly mutated in age-related clonal hematopoiesis (CH). Despite having opposed epigenetic functions, these mutations are associated with increased all-cause mortality and a low risk for progression to hematological neoplasms. While individual impacts on the epigenome have been described using different model systems, the phenotypic complexity in humans remains to be elucidated.

Genomic epidemiology reveals the dominance of Hennepin County in the transmission of SARS-CoV-2 in Minnesota from 2020 to 2022.

We analyzed over 22,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes of patient samples tested at Mayo Clinic Laboratories during a 2-year period in the COVID-19 pandemic, which included Alpha, Delta, and Omicron variants of concern to examine the roles and relationships of Minnesota virus transmission. We found that Hennepin County, the most populous county, drove the transmission of SARS-CoV-2 viruses in the state after including the formation of earlier clades including 20A, 20C, and 20G, as well as variants of concern Alpha and Delta. We also found that Hennepin County was the source for most of the county-to-county introductions after an initial predicted introduction with the virus in early 2020 from an international source, while other counties acted as transmission "sinks.

Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022.

SARS-CoV-2 has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of virus evolution and spread, and to inform policy decisions. We sequenced viral genomes from over 22,000 patient samples tested at Mayo Clinic Laboratories between 2020-2022 and use Bayesian phylodynamics to describe county and regional spread in Minnesota. The earliest introduction into Minnesota was to Hennepin County from a domestic source around January 22, 2020; six weeks before the first confirmed case in the state.

Convulsive Status Epilepticus Induced by Electroconvulsive Therapy in a Patient with Major Depression.

Electroconvulsive therapy (ECT) is a well-known, safe, and efficient treatment for a variety of psychiatric diseases. We present here an unusual case of a 34-year-old patient with major depression, who developed convulsive status epilepticus persistent for eight days in connection to her first ECT-a very uncommon but serious complication. The patient was, prior to ECT treatment, treated with lithium carbonate and clomipramine for her depression.

Improved Characterization of Complex β-Globin Gene Cluster Structural Variants Using Long-Read Sequencing.

Complex insertion-deletion (indel) events in the globin genes manifest in widely variable clinical phenotypes. Many are incompletely characterized because of a historic lack of efficient methods. A more complete assessment enables improved prediction of clinical impact, which guides emerging therapeutic choices.

Characterization of a dual media system for culturing primary normal and Fuchs endothelial corneal dystrophy (FECD) endothelial cells.

Primary cultures of human corneal endothelial cells (HCECs) are an important model system for studying the pathophysiology of corneal endothelium. The purpose of this study was to identify and validate an optimal primary culture model of normal and Fuchs endothelial corneal dystrophy (FECD) endothelial cells by comparing cell morphology and marker expression under different media conditions to in vivo donor tissues. Primary and immortalized HCECs, isolated from normal and FECD donors, were cultured in proliferation media (Joyce, M4, Bartakova) alone or sequentially with maturation media (F99, Stabilization 1, M5).

Cardiovascular autonomic neuropathy in patients with schizophrenia.

Background: Cardiovascular autonomic neuropathy (CAN) is an independent predictor of cardiovascular disease (CVD) in patients with diabetes as well as in patients with pre-diabetes and metabolic syndrome. Patients with schizophrenia have an increased rate of metabolic syndrome, pre-diabetes and diabetes as compared to the general population. Despite of this, occurrence CAN has not been investigated in patient with schizophrenia.

Relationship of Body Mass Index With Fuchs Endothelial Corneal Dystrophy Severity and TCF4 CTG18.1 Trinucleotide Repeat Expansion.

Purpose: To investigate the association of body mass index (BMI) with Fuchs endothelial corneal dystrophy (FECD) severity and TCF4 CTG18.1 expansion.

Methods: A total of 343 patients with FECD were enrolled from the Mayo Clinic.

Disease Expression and Familial Transmission of Fuchs Endothelial Corneal Dystrophy With and Without CTG18.1 Expansion.

Purpose: To characterize inheritance, penetrance, and trinucleotide repeat expansion stability in Fuchs endothelial corneal dystrophy (FECD).

Methods: One thousand unrelated and related subjects with and without FECD were prospectively recruited. CTG18.

Identification of Possible Risk Variants of Familial Strabismus Using Exome Sequencing Analysis.

Purpose: To investigate candidate genes associated with familial strabismus and propose a theory of their interaction in familial strabismus associated with early neurodevelopment.

Methods: Eighteen families, including 53 patients diagnosed with strabismus and 34 unaffected family members, were analyzed. All patients with strabismus and available unaffected family members were evaluated using whole exome sequencing.

Chromosomal Junction Detection from Whole-Genome Sequencing on Formalin-Fixed, Paraffin-Embedded Tumors.

DNA junctions (DNAJs) frequently impact clinically relevant genes in tumors and are important for diagnostic and therapeutic purposes. Although routinely screened through fluorescence in situ hybridization assays, such testing only allows the interrogation of single-gene regions or known fusion partners. Comprehensive assessment of DNAJs present across the entire genome can only be determined from whole-genome sequencing.

Transplant chimerism in porcine structural vascularized bone allotransplants.

Background: Bone allotransplant viability can be maintained long-term by implanting arteriovenous (AV) bundles and creating an autogenous neoangiogenic circulation. Only short-term immunosuppression is required. This study investigates the origin of viable osteocytes observed in areas of active bone remodeling in orthotopically transplanted tibiae in a Yucatan mini-pig model.

Correction to: Recommendations for performance optimizations when using GATK3.8 and GATK4.

Following publication of the original article [1], the author explained that Table 2 is displayed incorrectly. The correct Table 2 is given below. The original article has been corrected.

Recommendations for performance optimizations when using GATK3.8 and GATK4.

Background: Use of the Genome Analysis Toolkit (GATK) continues to be the standard practice in genomic variant calling in both research and the clinic. Recently the toolkit has been rapidly evolving. Significant computational performance improvements have been introduced in GATK3.

Sentieon DNASeq Variant Calling Workflow Demonstrates Strong Computational Performance and Accuracy.

As reliable, efficient genome sequencing becomes ubiquitous, the need for similarly reliable and efficient variant calling becomes increasingly important. The Genome Analysis Toolkit (GATK), maintained by the Broad Institute, is currently the widely accepted standard for variant calling software. However, alternative solutions may provide faster variant calling without sacrificing accuracy.

Amplification-free long-read sequencing of TCF4 expanded trinucleotide repeats in Fuchs Endothelial Corneal Dystrophy.

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.

Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients With Fuchs Endothelial Corneal Dystrophy.

Purpose: To investigate single nucleotide polymorphisms (SNPs) and trinucleotide repeat (TNR) expansion in the transcription factor 4 (TCF4) gene in a large cohort of German patients with Fuchs endothelial corneal dystrophy (FECD).

Methods: Genomic DNA was obtained from 398 patients with FECD and from 58 non-FECD controls. Thirty-seven previously reported SNPs were evaluated by genotyping.

Effect of Trinucleotide Repeat Expansion on the Expression of TCF4 mRNA in Fuchs' Endothelial Corneal Dystrophy.

Purpose: CTG trinucleotide repeat (TNR) expansion is frequently found in transcription factor 4 (TCF4) in Fuchs' endothelial corneal dystrophy (FECD), though the effect of TNR expansion on FECD pathophysiology remains unclear. The purpose of this study was to evaluate the effect of TNR expansion on TCF4 expression in corneal endothelium of patients with FECD.

Methods: Peripheral blood DNA and Descemet membrane with corneal endothelium were obtained from 203 German patients with FECD.

Familial chronic megacolon presenting in childhood or adulthood: Seeking the presumed gene association.

Objective: We identified a pedigree over five generations with 49 members, some of whom had chronic megacolon presenting in adolescence or adulthood. We aimed to assess the genetic cause of chronic megacolon through clinical and DNA studies.

Design: After ethical approval and informed consent, family members provided answers to standard bowel disease questionnaires, radiological or surgical records, and DNA (buccal mucosal scraping).