Dissecting the Genetic Architecture of Intracranial Aneurysms.

Background: The genetic risk of intracranial aneurysm (IA) development has been ascribed to the genetic risk of smoking exposure and hypertension. The relationship of IA to other cardiovascular traits and the contribution of IA risk loci to aberrant gene programs within cerebrovascular cell types remains unclear.

Methods: We performed a genome-wide association study in the Million Veteran Program and Finnish cohort study testing association of roughly 25 million DNA variants with unruptured IA (4694 cases and 877 091 controls) in individuals of European, African, and Hispanic ancestries.

Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aortic root or ascending/descending aorta. TAA is a heritable disease that can be potentially life threatening. While 10%-20% of TAA cases are caused by rare, pathogenic variants in single genes, the origin of the majority of TAA cases remains unknown.

Pattern of genomic variation in SARS-CoV-2 (COVID-19) suggests restricted nonrandom changes: Analysis using Shewhart control charts.

SARS-CoV-2 is a member of the Coronavirus family which recently originated from the Wuhan province of China and spread very rapidly through the world infecting more than 4 million people. In the past, other Coronaviruses have also been found to cause human infection, but not as widespread as COVID-19. Since Coronavirus sequences constantly change due to mutation and recombination, it is important to understand the pattern of changes and likely path the virus can take in the future.

Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits.

GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer.

Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported.

Chromatin organization modulates the origin of heritable structural variations in human genome.

Structural variations (SVs) in the human genome originate from different mechanisms related to DNA repair, replication errors, and retrotransposition. Our analyses of 26 927 SVs from the 1000 Genomes Project revealed differential distributions and consequences of SVs of different origin, e.g.

Transcriptome and epigenome landscape of human cortical development modeled in organoids.

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors.

De novo genome and transcriptome analyses provide insights into the biology of the trematode human parasite Fasciolopsis buski.

Many trematode parasites cause infection in humans and are thought to be a major public health problem. Their ecological diversity in different regions provides challenging questions on evolution of these organisms. In this report, we perform transcriptome analysis of the giant intestinal fluke, Fasciolopsis buski, using next generation sequencing technology.

Classification of pathogenic microbes using a minimal set of single nucleotide polymorphisms derived from whole genome sequences.

In a context specific manner, Intra-species genomic variation plays an important role in phenotypic diversity observed among pathogenic microbes. Efficient classification of these pathogens is important for diagnosis and treatment of several infectious diseases. NGS technologies have provided access to wealth of data that can be utilized to discover important markers for pathogen classification.

Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis.

Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks postconception) using clonal cell populations. We detected 200 to 400 single-nucleotide variations (SNVs) per cell.

Complex multifractal nature in Mycobacterium tuberculosis genome.

The mutifractal and long range correlation (C(r)) properties of strings, such as nucleotide sequence can be a useful parameter for identification of underlying patterns and variations. In this study C(r) and multifractal singularity function f(α) have been used to study variations in the genomes of a pathogenic bacteria Mycobacterium tuberculosis. Genomic sequences of M.

Analysis of IS6110 insertion sites provide a glimpse into genome evolution of Mycobacterium tuberculosis.

Insertion sequence (IS) 6110 is found at multiple sites in the Mycobacterium tuberculosis genome and displays a high degree of polymorphism with respect to copy number and insertion sites. Therefore, IS6110 is considered to be a useful molecular marker for diagnosis and strain typing of M. tuberculosis.

De novo transcriptome sequencing and analysis of the cereal cyst nematode, Heterodera avenae.

The cereal cyst nematode (CCN, Heterodera avenae) is a major pest of wheat (Triticum spp) that reduces crop yields in many countries. Cyst nematodes are obligate sedentary endoparasites that reproduce by amphimixis. Here, we report the first transcriptome analysis of two stages of H.

Next-Generation Anchor Based Phylogeny (NexABP): constructing phylogeny from next-generation sequencing data.

Whole genome sequences are ideally suited for deriving evolutionary relationship among organisms. With the availability of Next Generation sequencing (NGS) datasets in an unprecedented scale, it will be highly desirable if phylogenetic analysis can be carried out using short read NGS data. We described here an anchor based approach NexABP for phylogenetic construction of closely related strains/isolates from NGS data.

Genetic heterogeneity revealed by sequence analysis of Mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients.

Background: Tuberculosis remains a major public health problem. Clinical tuberculosis manifests often as pulmonary and occasionally as extra-pulmonary tuberculosis. The emergence of drug resistant tubercle bacilli and its association with HIV is a formidable challenge to curb the spread of tuberculosis.