The Experts below are selected from a list of 2685 Experts worldwide ranked by ideXlab platform

Thomas Liehr - One of the best experts on this subject based on the ideXlab platform.

  • about classical molecular genetics cytogenetic and molecular cytogenetic data not considered by Genome Reference Consortium and thus not included in Genome browsers like ucsc ensembl or ncbi
    Molecular Cytogenetics, 2021
    Co-Authors: Thomas Liehr
    Abstract:

    The Genome Reference Consortium (GRC) has according to its own statement the “mission to improve the human Reference Genome assembly, correcting errors and adding sequence to ensure it provides the best representation of the human Genome to meet basic and clinical research needs”. Data from GRC is included in Genome browsers like UCSC (University of California, Santa Cruz), Ensembl or NCBI (National Center for Biotechnology Information) and are thereby bases for scientific and diagnostically working human genetic community. Here long standing knowledge deriving from classical molecular genetic, cytogenetic and molecular cytogenetic data, not being considered yet by GRC was revisited. There were three major points identified: (1) GRC missed to including three chromosomal subbands, each, for 1q32.1, 2p21, 5q13.2, 6p22.3 and 6q21, which were defined by International System for Human Cytogenetic Nomenclature (ISCN) already back in 1980s; instead GRC included additional 6 subbands not ever recognized by ISCN. (2) GRC defined 34 chromosomal subbands of 0.1 to 0.9 Mb in size, while it is general agreement of cytogeneticists that it unlikely to detect chromosomal aberrations below 1–2 Mb in size by GTG-banding. And (3): still all sequences used in molecular cytogenetic routine diagnostics to detect heterochromatic and/ or pericentromeric satellite DNA sequences within the human Genome are not included yet into human Reference Genome. For those sequences, localization and approximate sizes have been determined in the 1970s to 1990, and if included at least ~ 100 Mb of the human Genome sequence could be added to the Genome browsers. Overall, taking into account the here mentioned points and correcting and including the data will definitely provide to the still not being completely finished mapping of the human Genome.

John A Tainer - One of the best experts on this subject based on the ideXlab platform.

  • cancer mutational burden is shaped by g4 dna replication stress and mitochondrial dysfunction
    Progress in Biophysics & Molecular Biology, 2019
    Co-Authors: Albino Bacolla, Zamal Ahmed, John A Tainer
    Abstract:

    A hallmark of cancer is genomic instability, which can enable cancer cells to evade therapeutic strategies. Here we employed a computational approach to uncover mechanisms underlying cancer mutational burden by focusing upon relationships between 1) translocation breakpoints and the thousands of G4 DNA-forming sequences within retrotransposons impacting transcription and exemplifying probable non-B DNA structures and 2) transcriptome profiling and cancer mutations. We determined the location and number of G4 DNA-forming sequences in the Genome Reference Consortium Human Build 38 and found a total of 358,605 covering ∼13.4 million bases. By analyzing >97,000 unique translocation breakpoints from the Catalogue Of Somatic Mutations In Cancer (COSMIC), we found that breakpoints are overrepresented at G4 DNA-forming sequences within hominid-specific SVA retrotransposons, and generally occur in tumors with mutations in tumor suppressor genes, such as TP53. Furthermore, correlation analyses between mRNA levels and exome mutational loads from The Cancer Genome Atlas (TCGA) encompassing >450,000 gene-mutation regressions revealed strong positive and negative associations, which depended upon tissue of origin. The strongest positive correlations originated from genes not listed as cancer genes in COSMIC; yet, these show strong predictive power for survival in most tumor types by Kaplan-Meier estimation. Thus, correlation analyses of DNA structure and gene expression with mutation loads complement and extend more traditional approaches to elucidate processes shaping genomic instability in cancer. The combined results point to G4 DNA, activation of cell cycle/DNA repair pathways, and mitochondrial dysfunction as three major factors driving the accumulation of somatic mutations in cancer cells.

Williams, Robert W - One of the best experts on this subject based on the ideXlab platform.

  • The Genome sequence of the Norway rat, Rattus norvegicus Berkenhout 1769.
    'Organisation for Economic Co-Operation and Development (OECD)', 2021
    Co-Authors: Howe Kerstin, Dwinell Melinda, Shimoyama Mary, Corton Craig, Betteridge Emma, Dove Alexander, Quail, Michael A, Smith Michelle, Saba Laura, Williams, Robert W
    Abstract:

    We present a Genome assembly from an individual male Rattus norvegicus (the Norway rat; Chordata; Mammalia; Rodentia; Muridae). The Genome sequence is 2.44 gigabases in span. The majority of the assembly is scaffolded into 20 chromosomal pseudomolecules, with both X and Y sex chromosomes assembled. This Genome assembly, mRatBN7.2, represents the new Reference Genome for R. norvegicus and has been adopted by the Genome Reference Consortium

Robert W. Williams - One of the best experts on this subject based on the ideXlab platform.

Albino Bacolla - One of the best experts on this subject based on the ideXlab platform.

  • cancer mutational burden is shaped by g4 dna replication stress and mitochondrial dysfunction
    Progress in Biophysics & Molecular Biology, 2019
    Co-Authors: Albino Bacolla, Zamal Ahmed, John A Tainer
    Abstract:

    A hallmark of cancer is genomic instability, which can enable cancer cells to evade therapeutic strategies. Here we employed a computational approach to uncover mechanisms underlying cancer mutational burden by focusing upon relationships between 1) translocation breakpoints and the thousands of G4 DNA-forming sequences within retrotransposons impacting transcription and exemplifying probable non-B DNA structures and 2) transcriptome profiling and cancer mutations. We determined the location and number of G4 DNA-forming sequences in the Genome Reference Consortium Human Build 38 and found a total of 358,605 covering ∼13.4 million bases. By analyzing >97,000 unique translocation breakpoints from the Catalogue Of Somatic Mutations In Cancer (COSMIC), we found that breakpoints are overrepresented at G4 DNA-forming sequences within hominid-specific SVA retrotransposons, and generally occur in tumors with mutations in tumor suppressor genes, such as TP53. Furthermore, correlation analyses between mRNA levels and exome mutational loads from The Cancer Genome Atlas (TCGA) encompassing >450,000 gene-mutation regressions revealed strong positive and negative associations, which depended upon tissue of origin. The strongest positive correlations originated from genes not listed as cancer genes in COSMIC; yet, these show strong predictive power for survival in most tumor types by Kaplan-Meier estimation. Thus, correlation analyses of DNA structure and gene expression with mutation loads complement and extend more traditional approaches to elucidate processes shaping genomic instability in cancer. The combined results point to G4 DNA, activation of cell cycle/DNA repair pathways, and mitochondrial dysfunction as three major factors driving the accumulation of somatic mutations in cancer cells.