Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing.

Prior studies have suggested the existence of reduced penetrance pathogenic variants (RPPVs) in BRCA1 and BRCA2 (BRCA) which pose challenges for patient counseling and care. Here, we sought to establish RPPVs as a new category of variants. Candidate BRCA RPPVs provided by two large clinical diagnostic laboratories were compiled to identify those with the highest likelihood of being a RPPV, based on concordant interpretations.

Canine mesenteric lymph nodes (MLNs) characterization by sc-RNAseq: insights compared to human and mouse MLNs.

In the human and veterinary fields, oral vaccines generate considerable interest. In dogs, these vaccines are newly developed, and understanding their mechanisms is crucial. Mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) are important sites for gastrointestinal mucosal induction, yet canine MLNs lack sufficient information.

Breast and colorectal cancer risks among over 6,000 CHEK2 pathogenic variant carriers: A comparison of missense versus truncating variants.

Background And Aims: Heterozygous truncating pathogenic variants (PVs) in CHEK2 confer a 1.5 to 3-fold increased risk for breast cancer and may elevate colorectal cancer risks. Less is known regarding missense variants.

Mucosal Vaccination with Live Attenuated Protects against Challenge in Wistar Rats.

(Bb) is a Gram-negative bacterium responsible for canine infectious respiratory disease complex (CIRDC). Several vaccines targeting this pathogen are currently licensed for use in dogs, but their mechanism of action and the correlates of protection are not fully understood. To investigate this, we used a rat model to examine the immune responses induced and the protection conferred by a canine mucosal vaccine after challenge.

Discordance between germline genetic findings and abnormal tumor immunohistochemistry staining of mismatch repair proteins in individuals with suspected Lynch syndrome.

Background And Aims: Tumor immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins is often used to guide germline genetic testing and variant classification for patients with suspected Lynch syndrome. This analysis examined the spectrum of germline findings in a cohort of individuals showing abnormal tumor IHC.

Methods: We assessed individuals with reported abnormal IHC findings and referred for testing with a six-gene syndrome-specific panel (n=703).

M448R and MGF505-7R: Two African Swine Fever Virus Antigens Commonly Recognized by ASFV-Specific T-Cells and with Protective Potential.

African swine fever (ASF) is today's number one threat for the global swine industry. Neither commercial vaccine nor treatment is available against ASF and, thus far, only live attenuated viruses (LAV) have provided robust protection against lethal ASF virus (ASFV) challenge infections. Identification of ASFV proteins inducing protective immune responses is one of the major challenges to develop safer and efficient subunit vaccines.

Pilot study of an occupational healthcare program to assess the SARS-CoV-2 infection and immune status of employees in a large pharmaceutical company.

Objective: To safeguard key workers involved in development and production of medicines and ensure business continuity, we developed an occupational healthcare program, performed by our company's occupational healthcare services, to assess the infection and immune status for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pilot program, conducted at our company facilities, evaluated the suitability of diagnostic tools in our setting for program upscaling.

Methods: We used different marketed diagnostics (including tests for antibodies against spike protein subunits S1 and S2 and nucleocapsid [N] protein) combined with medical history, symptoms and likelihood of infection.

Interpretation of BRCA2 Splicing Variants: A Case Series of Challenging Variant Interpretations and the Importance of Functional RNA Analysis.

A substantial proportion of pathogenic variants associated with an increased risk of hereditary cancer are sequence variants affecting RNA splicing. The classification of these variants can be complex when both non-functional and functional transcripts are produced from the variant allele. We present four BRCA2 splice site variants with complex variant interpretations (BRCA2 c.

High risk of breast cancer in women with biallelic pathogenic variants in CHEK2.

Purpose: Compared to breast cancer risk genes such as BRCA2, ATM, PALB2, and NBN, no defined phenotype is currently associated with biallelic pathogenic variants (PVs) in CHEK2. This study compared the prevalence of breast and other cancers in women with monoallelic and biallelic CHEK2 PVs.

Methods: CHEK2 PV carriers were identified through commercial hereditary cancer panel testing (09/2013-07/2019).

Efficacy of Bivalent Inactivated Vaccine Containing Insect Cell-Expressed Avian Influenza H5 and Egg-Based Newcastle Disease Virus (NDV) Against Dual Infection with Highly Pathogenic H5N1 and Velogenic NDV in Chickens.

The genetic evolution of highly pathogenic avian influenza (HPAI) in Egypt has developed a new clade H5N1 (2.2.1.

Genotype-associated differences in bursal recovery after infectious bursal disease virus (IBDV) inoculation.

T-cell immune responses were shown to play an important role in the regulation of infectious bursal disease virus (IBDV) replication and development of lesions in the bursa of Fabricius (BF) (bursal lesions) but also in the recovery from the infection. Studies suggested that the host-genotype influences T-cell responses during the acute phase of infection. Genotype-related differences in the recovery phase were not investigated so far.

Immune responses upon in ovo HVT-IBD vaccination vary between different chicken lines.

The genotype of chickens is assumed to be associated with variable immune responses. In this study a modern, moderate performing dual-purpose chicken line (DT) was compared with a high-performing layer-type (LT) as well as a broiler-type (BT) chicken line. One group of each genotype was vaccinated in ovo with a recombinant herpesvirus of turkeys expressing the virus protein VP2 of the infectious bursal disease virus (HVT-IBD) while one group of each genotype was left HVT-IBD unvaccinated (control group).

ICTV virus taxonomy profile: Picobirnaviridae.

Picobirnaviridae is a family of viruses with bi-segmented (rarely unsegmented) dsRNA genomes comprising about 4.4 kbp in total, with small, non-enveloped spherical virions. The family includes one genus (Picobirnavirus) grouping three genetic clusters with high sequence variability, two defined by viruses infecting vertebrates and a third with viruses found in invertebrates.

ICTV virus taxonomy profile: Birnaviridae.

Birnaviridae is a family of viruses with bi-segmented dsRNA genomes totalling about 6 kbp forming icosahedral, non-enveloped virions. The family includes four genera, members of three of which (Aquabirnavirus, Avibirnavirus and Blosnavirus) infect vertebrates (excluding mammals), whereas members of the fourth genus (Entomobirnavirus) infect insects. Each genus includes 1-3 species.

Prevalence of Variant Reclassification Following Hereditary Cancer Genetic Testing.

Importance: Variant reclassification is an important component of hereditary cancer genetic testing; however, there are few published data quantifying the prevalence of reclassification.

Objective: Retrospective cohort study of individuals who had genetic testing from 2006 through 2016 at a single commercial laboratory.

Design, Setting, And Participants: A retrospective cohort of individuals who had genetic testing between 2006 and 2016 at a single commercial laboratory was assessed.

Deletion of accessory genes 3a, 3b, 5a or 5b from avian coronavirus infectious bronchitis virus induces an attenuated phenotype both in vitro and in vivo.

Avian coronavirus infectious bronchitis virus (IBV) infects domestic fowl, resulting in respiratory disease and causing serious losses in unprotected birds. Its control is mainly achieved by using live attenuated vaccines. Here we explored the possibilities for rationally attenuating IBV to improve our knowledge regarding the function of IBV accessory proteins and for the development of next-generation vaccines with the recently established reverse genetic system for IBV H52 based on targeted RNA recombination and selection of recombinant viruses in embryonated eggs.

Chicken astrovirus as an aetiological agent of runting-stunting syndrome in broiler chickens.

Despite descriptions of runting-stunting syndrome (RSS) in broiler chickens dating back over 40 years, the aetiology has not yet been described. A novel chicken astrovirus (CkAstV) was isolated in an LMH liver cell line from the intestines of chickens affected with RSS. Clinical RSS is characterized by retarded growth and cystic crypt lesions in the small intestine.

Recombinant live attenuated avian coronavirus vaccines with deletions in the accessory genes 3ab and/or 5ab protect against infectious bronchitis in chickens.

Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens, causing severe economic losses in poultry industry worldwide. Live attenuated viruses are widely used in both the broiler and layer industry because of their efficacy and ability to be mass applied. Recently, we established a novel reverse genetics system based on targeted RNA recombination to manipulate the genome of IBV strain H52.

In Reply.

This Letter to the Editor responds to concerns regarding a recently published analysis of BRCA1 and BRCA2 variant classifications between a single testing laboratory (Myriad Genetic Laboratories) and a database of user‐submitted variant classifications (ClinVar).