Viral SARS-CoV-2 Rebound Rates in Linked Commercial Pharmacy-Based Testing and Health Care Claims.

Background: Viral SARS-CoV-2 rebound (viral RNA rebound) is challenging to characterize in large cohorts due to the logistics of collecting frequent and regular diagnostic test results. Pharmacy-based testing data provide an opportunity to study the phenomenon in a large population, also enabling subgroup analyses. The current real-world evidence approach complements approaches focused on smaller, prospective study designs.

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

The highly transmissible B.1.1.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

As of January of 2021, the highly transmissible B.1.1.

Rearrangement and allelic imbalance on chromosome 5 leads to homozygous deletions in the CDKN2A/2B tumor suppressor gene region in rat endometrial cancer.

The inbred BDII rat is a valuable experimental model for the genetic analysis of hormone-dependent endometrial adenocarcinoma (EAC). One common aberration detected previously by comparative genomic hybridization in rat EAC is loss affecting mostly the middle part of rat chromosome 5 (RNO5). First, we applied an RNO5-specific painting probe and four region-specific gene probes onto tumor cell metaphases from 21 EACs, and found that rearrangements involving RNO5 were common.

Amplification studies of MET and Cdk6 in a rat endometrial tumor model and their correlation to human type I endometrial carcinoma tumors.

Cancer is known to be a genetic disease that is both polygenic and heterogeneous, in most cases involving changes in several genes in a stepwise fashion. The spectrum of individual genes involved in the initiation and progression of cancer is greatly influenced by genetic factors unique to each patient. A study of complex diseases such as cancer is complicated by the genetic heterogeneous background and environmental factors in the human population.

Recurrent gene amplifications in human type I endometrial adenocarcinoma detected by fluorescence in situ hybridization.

Determining what genes are actively involved in tumor development is important, because they may provide targets for directed therapy. Human tumors are greatly heterogeneous with respect to etiology and genetic background, which complicates the identification of common genetic aberrations. In contrast, genetic and environmental variation can be in part controlled in experimental animals, which facilitates identification of the important changes.

Nonrandom pattern of chromosome aberrations in 17beta-estradiol-induced rat mammary tumors: indications of distinct pathways for tumor development.

Estrogens play an important role in breast cancer etiology and the ACI rat provides a novel animal model for defining the mechanisms through which estrogens contribute to mammary cancer development. In crossing experiments between the susceptible ACI strain and two resistant strains, COP (Copenhagen) and BN (Brown Norway), several quantitative trait loci (QTL) that affect development of 17beta-estradiol (E2)-induced mammary tumors have been defined. Using comparative genomic hybridization (CGH), we have analyzed cytogenetic aberrations in E2-induced mammary cancers and have found clear patterns of nonrandom chromosomal involvement.

Chromosome ideograms of the laboratory rat (Rattus norvegicus) based on high-resolution banding, and anchoring of the cytogenetic map to the DNA sequence by FISH in sample chromosomes.

A detailed banded ideogram representation of the rat chromosomes was constructed based on actual G-banded prometaphase chromosomes. The approach yielded 535 individual bands, a significant increase compared to previously presented ideograms. The new ideogram was adapted to the existing band nomenclature.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces genetic changes in murine intestinal tumours and cells with ApcMin mutation.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the mutagenic heterocyclic amines derived from cooked meat. In previous animal studies, spontaneous tumour formation in B6(Min/+) mice was associated with somatic loss of the wild-type Apc+ allele by loss of the entire chromosome 18 or by recombination. The objective of this study was to examine genetic changes caused by PhIP-exposure in a mouse intestinal cell line and in tumours from hybrid mice by keeping track of the chromosomes carrying the two Apc alleles.

Male and female germline specific expression of an EGFP reporter gene in a unique strain of transgenic rats.

A rat line was generated in which genomic integration of a ROSA-EGFP transgene resulted in exclusive expression of EGFP in the germ cells of both sexes. EGFP expression was uniform and robust in cleavage stage embryos beginning at the late 2-cell stage and continuing through blastocyst development where expression became restricted to cells of the inner cell mass. Subsequent analysis showed high EGFP expression exclusively in primordial, embryonic, and adult germ cells.

Oncogene amplification in the proximal part of chromosome 6 in rat endometrial adenocarcinoma as revealed by combined BAC/PAC FISH, chromosome painting, zoo-FISH, and allelotyping.

The inbred BDII rat is a valuable experimental model for the genetic analysis of endometrial adenocarcinoma (EAC). One common aberration detected by comparative genomic hybridization in rat EAC was gain/amplification affecting the proximal part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting probes onto tumor cell metaphase preparations in order to detect and characterize gross RNO6 aberrations.

Cytogenetic aberrations in spontaneous endometrial adenocarcinomas in the BDII rat model as revealed by chromosome banding and comparative genome hybridization.

Female rats of the inbred strain BDII are genetically predisposed to endometrial estrogen-dependent adenocarcinomas (EAC). More than 90% of them spontaneously develop this tumor type before the age of 24 months. In order to dissect out the genetic components behind these tumors we have made crosses between BDII females and rats from 2 other strains that are nonsusceptible to EAC.

Assessment of allele dosage at polymorphic microsatellite loci displaying allelic imbalance in tumors by means of quantitative competitive-polymerase chain reaction.

Analysis of allelic imbalance at polymorphic marker loci is usually employed to identify chromosomal regions affected by recurrent aberrations in tumor genomes. Such regions are likely to harbor genes involved in the onset and/or progression of cancer. Although often used to identify regions of loss of heterozygosity caused by deletions/rearrangements near tumor suppressor gene loci, allelic imbalance can also reflect regional amplification, indicating the presence of oncogenes.

Allelic imbalance on chromosome 10 in rat endometrial adenocarcinomas.

Earlier work using comparative genome hybridization (CGH) has shown that rat chromosome 10 (RNO10) is frequently involved in cytogenetic aberrations in BDII rat endometrial adenocarcinomas (EAC). Relative reduction in copy number (chromosomal deletions) was seen in the proximal to middle part of the chromosome, whereas there were increases in copy number in the distal part. The occurrence of RNO10 aberrations was further analyzed in DNA from primary tumor material from 42 EACs and 3 benign endometrial tumors using allelotyping of microsatellite markers.

Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations.

The targeted inactivation of oncogenes may be a specific and effective treatment for cancer. However, because human cancers are the consequence of multiple genetic changes, the inactivation of one oncogene may not be sufficient to cause sustained tumor regression. Moreover, cancers are genomically unstable and may readily compensate for the inactivation of a single oncogene.

Recurrent allelic imbalance at the rat Pten locus in DMBA-induced fibrosarcomas.

The tumor-suppressor gene PTEN (phosphatase and tensin homolog) is frequently inactivated in different types of human tumors. Less is known about the involvement of the homologous gene Pten in animal model systems of cancer. By sequencing one of the introns of rat Pten, we found an informative intragenic PCR marker suitable for genetic studies.

Evolutionary aspects of the genomic organization of rat chromosome 10.

Using FISH and RH mapping a chromosomal map of rat chromosome 10 (RNO10) was constructed. Our mapping data were complemented by other published data and the final map was compared to maps of mouse and human chromosomes. RNO10 contained segments homologous to mouse chromosomes (MMU) 11, 16 and 17, with evolutionary breakpoints between the three segments situated in the proximal part of RNO10.

Chromosome assignment of Cd36 transgenes in two rat SHR lines by FISH and linkage mapping of transgenic insert in the SHR-TG19 line.

The chromosome position of the Cd36 insert was determined by FISH in two rat transgenic lines (SHR/Ola-TgN(EF1aCd36)10Ipcv (SHR-TG10) and SHR/Ola-TgN(EF1aCd36)19Ipcv (SHR-TG19). The Cd36 transgene construct labelled with digoxigenin-11-dNTP was used as a probe in the FISH analysis. In accord with the previous finding that the SHR-TG10 harbours 6-8 copies of the transgene, the signals from both metaphase and interphase nuclei of SHR-TG10 preparations were rather strong and the probe hybridized to both copies of chromosome 1 at band q55.

Analysis of chromosomal aberrations involving chromosome 1q31-->q53 in a DMBA-induced rat fibrosarcoma cell line: amplification and overexpression of Jak2.

In a study of DMBA-induced rat fibrosarcomas we repeatedly found deletions and/or amplifications in the long arm of rat chromosome 1 (RNO1). Comparative genome hybridization showed that there was amplification involving RNO1q31-->q53 in one of the DMBA-induced rat fibrosarcoma tumors (LB31) and a cell culture derived from it. To identify the amplified genes we physically mapped rat genes implicated in cancer and analyzed them for signs of amplification.

Identification, characterization and cytogenetic mapping of a yeast Vps54 homolog in rat and mouse.

A novel gene, VPS54-like (Vps54l), is described in the rat that is homologous to the yeast Vps54 gene which is known to be involved in intracellular protein sorting. Furthermore, Vps54-related sequences of human, mouse, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana could be identified in the EMBL/GenBank/DDBJ database. Each of the deduced amino acid sequences of the Vps54 genes in these species contain a coiled-coil region and eight to 13 dileucine motifs.

The functional significance of absence: the chromosomal segment harboring Tp53 is absent from the T55 rat radiation hybrid mapping panel.

The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2-6%).

High-density marker loss of heterozygosity analysis of rat chromosome 10 in endometrial adenocarcinoma.

Endometrial cancer is a disease with serious impact on the human population, but not much is known about genetic factors involved in this complex disease. Female BDII rats are genetically predisposed to spontaneous endometrial carcinoma, and the BDII inbred strain provides an experimental animal model for endometrial carcinoma development. In the present study, BDII females were crossed with males from two nonsusceptible inbred rat strains.

Independent amplification of two gene clusters on chromosome 4 in rat endometrial cancer: identification and molecular characterization.

The BDII rat is genetically predisposed to hormone-dependent endometrial adenocarcinoma and was used to model human cancer. Tumors arising spontaneously in strain crosses involving BDII rats were analyzed by means of comparative genome hybridization. The most common aberration was amplification of the proximal region of rat chromosome 4, centered around bands q12-q22.

A dual-color FISH gene map of the proximal region of rat Chromosome 4 and comparative analysis in human and mouse.

The development and refinement of the rat genome map is a prerequisite for a continued qualified and fruitful use of this model system for the study of complex traits. In two distinct rat cancer models, recurrent amplification affecting the proximal region of rat Chr 4 was detected. To further characterize this region, we turned to the evolutionarily conserved chromosome segments in human Chr 7 and mouse Chrs 5 and 6 to identify functional and positional candidate genes.