Differentially Expressed Gene Patterns in Ascarid-Infected Chickens of Higher- or Lower-Performing Genotypes

Here, we describe the first transcriptomic investigation of the peripheral blood of chickens exposed to Ascaridia galli and Heterakis gallinarum infections. We investigated differentially expressed gene (DEG) patterns in two chicken genotypes with either a higher (Lohmann Brown Plus, LB) or lower (Lohmann Dual, LD) laying performance level. The hens were experimentally coinfected with A. galli and H. gallinarum, and their worm burdens and infection parameters were determined six weeks post infection. Based on most representative infection parameters, the hens were clustered into lower- and higher-infection intensity classes. We identified a total of 78 DEGs contributing to infection-related phenotypic variation in the two genotypes. Our data showed significant upregulation of Guanylate Binding Protein 7 (GBP7) in LD hens, making it a promising candidate for tolerance to ascarid infections in chickens. Gene ontology analysis revealed higher transcriptome activity related to biological processes such as "response to external stimulus" in LB hens, implying a higher stress response in this genotype. In contrast, LD hens showed higher transcriptomic expression of genes related to ontology classes that are possibly associated with a higher tolerance to infections. These findings may help explain why lower-performing genotypes (i.e., LD) are less sensitive to infections in terms of maintaining their performance

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

The Genetics of Uveal Melanoma: Overview and Clinical Relevance

Over the last ten years, much has been learnt about the genetic characteristics and genetic evolution of uveal melanoma. It has been shown that uveal melanoma differs fundamentally from non-uveal melanoma and is an independent genetic subtype. Compared to other tumours, uveal melanoma has a low mutational burden. There are recurring chromosomal aberrations with losses of 1p, 6q, 8p and 16q, gains of 6p and 8q, and the presence of monosomy 3. GNAQ, GNA11, PLCB4, CYSLTR2, MAPKAPK5, as well as mutations in BAP1, SF3B1, SRSF2 and EIF1AX, the latter being linked to a higher risk of metastasis, have been identified as significantly mutated genes. In rare cases, a BAP1 germline mutation may also be present. In addition to higher risk of uveal melanoma, this variant is also linked with other tumours. In this case, additional work-up, genetic counselling and screening of family members should be offered. While the knowledge about the genetic characteristics of uveal melanoma is already routinely used for diagnostic and prognostic purposes, targeted genotype-dependent therapy of uveal melanoma is currently still missing

Box-and-whisker plot visualization of the percentage change of Total Area Fragment values from peptides between deglycosylated and glycosylated samples in the course of pregnancy and post-partum.

Box-and-whisker plot visualization of the percentage change of Total Area Fragment values from peptides between deglycosylated and glycosylated samples in the course of pregnancy and post-partum.</p

Mean percentage change of Total Area Fragment values from boPAGs between deglycosylated (degly) and glycosylated (gly) samples in the course of pregnancy and post-partum.

Mean percentage change of Total Area Fragment values from boPAGs between deglycosylated (degly) and glycosylated (gly) samples in the course of pregnancy and post-partum.</p

Fig 4 -

Relative proportions among the different pregnancy states for (a) glycosylated samples and (b) deglycosylated samples. Note the different basic population of Total Area Fragment (a = 4,774,159; b = 7,567,626).</p

Gel images of seven different purified bovine pregnancy-associated glycoproteins (boPAG) samples from four different pregnancy stages.

The protein samples (1 μg/lane) were either enzymatically deglycosylated with Peptide-N-Glycosidase F (PNGase F) (lane 4, 6, 8, 10) or left untreated (lane 3, 5, 7, 9). Molecular weights of the marker (M)-bands (lane 1, 2) are indicated on the left (kDa). Early pregnancy samples of lane 7 (b) and lane 8 (b) were not analyzed by mass spectrometry.</p

List of proteins and proteotypic peptides.

List of proteins and proteotypic peptides.</p