Copy number variation in the bovine genome

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs), which represent a significant source of genetic diversity in mammals, have been shown to be associated with phenotypes of clinical relevance and to be causative of disease. Notwithstanding, little is known about the extent to which CNV contributes to genetic variation in cattle.</p> <p>Results</p> <p>We designed and used a set of NimbleGen CGH arrays that tile across the assayable portion of the cattle genome with approximately 6.3 million probes, at a median probe spacing of 301 bp. This study reports the highest resolution map of copy number variation in the cattle genome, with 304 CNV regions (CNVRs) being identified among the genomes of 20 bovine samples from 4 dairy and beef breeds. The CNVRs identified covered 0.68% (22 Mb) of the genome, and ranged in size from 1.7 to 2,031 kb (median size 16.7 kb). About 20% of the CNVs co-localized with segmental duplications, while 30% encompass genes, of which the majority is involved in environmental response. About 10% of the human orthologous of these genes are associated with human disease susceptibility and, hence, may have important phenotypic consequences.</p> <p>Conclusions</p> <p>Together, this analysis provides a useful resource for assessment of the impact of CNVs regarding variation in bovine health and production traits.</p

Molecular characterization and temporal expression profiling of presenilins in the developing porcine brain

<p>Abstract</p> <p>Background</p> <p>The transmembrane presenilin (PSEN) proteins, PSEN1 and PSEN2, have been proposed to be the catalytic components of the γ-secretase protein complex, which is an intramembranous multimeric protease involved in development, cell regulatory processes, and neurodegeneration in Alzheimer's disease. Here we describe the sequencing, chromosomal mapping, and polymorphism analysis of PSEN1 and PSEN2 in the domestic pig (<it>Sus scrofa domesticus</it>).</p> <p>Results</p> <p>The porcine presenilin proteins showed a high degree of homology over their entire sequences to the PSENs from mouse, bovine, and human. PSEN1 and PSEN2 transcription was examined during prenatal development of the brain stem, hippocampus, cortex, basal ganglia, and cerebellum at embryonic days 60, 80, 100, and 114, which revealed distinct temporal- and tissue-specific expression profiles. Furthermore, immunohistochemical analysis of PSEN1 and PSEN2 showed similar localization of the proteins predominantly in neuronal cells in all examined brain areas.</p> <p>Conclusion</p> <p>The data provide evidence for structural and functional conservation of PSENs in mammalian lineages, and may suggest that the high sequence similarity and colocalization of PSEN1 and PSEN2 in brain tissue reflect a certain degree of functional redundancy. The data show that pigs may provide a new animal model for detailed analysis of the developmental functions of the PSENs.</p

Long-term detection of SARS-CoV-2 antibodies after infection and risk of re-infection

OBJECTIVES: To evaluate long-term sensitivity for detection of total antibodies against SARS-CoV-2 METHODS: From week 41, 2020, through week 26, 2021, all Danish blood donations were tested for SARS-CoV-2 antibodies with the Wantai assay. The results were linked with polymerase chain reaction (PCR) test results from the Danish Microbiological Database (MiBa). RESULTS: During the study period, 105,646 non-vaccinated Danish blood donors were tested for SARS-CoV-2 antibodies, and 3,806 (3.6%) had a positive PCR test before the blood donation. Among the donors with a positive PCR test, 94.2% subsequently also had a positive antibody test. The time between the positive PCR test and the antibody test was up to 15 months and there was no evidence of a decline in proportion with detectable antibodies over time. A negative serological result test was associated with a higher incidence of re-infection (Incidence Rate Ratio = 0.102 (95% confidence interval (CI): 0.039–0.262)). CONCLUSION: Among healthy blood donors, 94.2% developed SARS-CoV-2 antibodies after infection, and a lack of detectable antibodies was associated with re-infection

Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in \u3ci\u3eD374Y\u3c/i\u3e-PCSK9 Hypercholesterolemic Minipigs

Background—Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma (TCFA). Methods and Results—D374Y-PCSK9 hypercholesterolemic minipigs (N=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately post-stent, 19, and 34 weeks and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially-collected histological sections and co-registered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ~3-fold higher downstream of the SMS compared to both upstream of the SMS and in the control artery (pppp\u3c0.005). Conclusions—These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of TCFA

Våra dialekter

Våra dialekter Innehållsförteckning – Inledaren: Stolthet och identitet av Pia Prost – Finlands svenska dialekter mår bra av Thure Malmberg – Abborrar, strömmingsnät, sjömän och en droppe i havet av Carola Ekrem – Dialektgränsen i Skärgårdshavet av Ann-Marie Ivars – För dig som vill lära dig hootsjärskå! av Ulla Mattsson-Wiklén – Lokalblad på Korpo ger dialekthistorier nytt liv av Ida-Kajsa Johansson – Svenska spår i skärgårdskommunen Gustavs av Charlotte von Haartman – På Bärgöijen av Pia Prost – ”Tig, det får man på Kökar det” av Kristin Mattsson – Hälsningar från Nöute av Kristin Mattsson – Havet tog bror och barn men livsglädjen är kvar av Thure Malmberg – Skärgårdsfotografen Bo Isomaa – Marinbiologin moderniseras av Anna Törnroos-Remes och Erik Bonsdorff – Skyddsfonden för Skärgårdshavet av Tove Holm – Kött på förvittrade ben av Kasper Westerlund – Bokhörnan: Spång över gränsälv i nordiskt nålsöga – 40 år av nordiskt skärgårdssamarbete – historien 2008–2017 av Lars Nyberg – Skärgårdens historia av Christian Pleijel – De vill använda vatten två gånger av Christian Pleijel – Skärinytt – Sista bilde

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants’ PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges

A Snapshot of CNVs in the Pig Genome

Recent studies of mammalian genomes have uncovered the extent of copy number variation (CNV) that contributes to phenotypic diversity, including health and disease status. Here we report a first account of CNVs in the pig genome covering part of the chromosomes 4, 7, 14, and 17 already sequenced and assembled. A custom tiling oligonucleotide array was used with a median probe spacing of 409 bp for screening 12 unrelated Duroc boars that are founders of a large family material. After a strict CNV calling pipeline, 37 copy number variable regions (CNVRs) across all four chromosomes were identified, with five CNVRs overlapping segmental duplications, three overlapping pig unigenes and one overlapping a RefSeq pig mRNA. This CNV snapshot analysis is the first of its kind in the porcine genome and constitutes the basis for a better understanding of porcine phenotypes and genotypes with the prospect of identifying important economic traits

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.Peer reviewe

Polycystic ovary syndrome

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.Robert J Norman, Ruijin Wu and Marcin T Stankiewic