The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes.
Reduction of methane emission may become necessary for ...sustainable milk production. Several studies indicate a relationship between rumination time and the level of methane emission. The objectives of the current study were to estimate environmental factors affecting daily rumination time in high-yielding dairy cattle, genetic parameters for rumination time across parities, and environmental and genetic correlations between rumination time and economic traits, and to predict the consequence of inclusion of this trait in the Israeli breeding index. The data included more than 30 million daily records from 77,697 Israeli Holstein cows for rumination time and milk production. A lactation measure of daily rumination time per cow was computed as the mean of the residuals from a linear model analysis with rumination time as the dependent variable. The independent variables were parity and the square root, linear, quadradic and inverse of DIM by parity. Because of the shape of the lactation curve for rumination time, separate linear model analyses were performed for records up to 40 DIM and records with >40 DIM. The phenotypic correlation between first- and second-parity lactations for rumination time was almost 0.8, and close to 0.7 for milk. The heritability of lactation rumination time was close to 0.44 for parities 1 to 3. Heritability for milk production decreased from 0.5 in first parity to 0.3 in third parity. For both traits, genetic correlations among parities were all >0.9. Thus, for routine genetic analysis of rumination time, records in the different parities can be considered the same trait. The genetic correlation between rumination time and milk on first parity was 0.25 and increased slightly with increase in parity. Genetic correlations between rumination time, based on the first 40 DIM, were economically unfavorable with retained placenta but economically favorable with metritis, ketosis, and displaced abomasum. Genetic correlations between rumination time and the 9 traits included in the Israeli breeding index (milk, fat, and protein production; SCS; female fertility; herd-life; milk production persistency; calving ease; and calf mortality) were all economically favorable, except for the correlation of 0.17 with SCS. With the current index, daily rumination time with a current mean of 536 min and SD of 90 min is expected to increase by 11 min/d after 10 yr of selection. Inclusion of this trait with a positive index weight equivalent to 10% of the index should increase rumination time by 19 min. All changes in expected gains due to inclusion of rumination time in the index were economically positive, except for fat and SCS. Inclusion of rumination time in the index should result in 1 kg less gain in fat, a miniscule gain of 0.03 for SCS; and gains of 1.5 kg protein, 0.3% female fertility, and 5 d herd-life. Even though the case for a genetic correlation between rumination time and methane emission is still weak, inclusion of this trait in the commercial index may be justified, considering that equipment is now commercially available for routine recording at reasonable cost.
DNA methylation is of paramount importance for mammalian embryonic development. DNA methylation has numerous functions: it is implicated in the repression of transposons and genes, but is also ...associated with actively transcribed gene bodies and, in some cases, with gene activation per se. In recent years, sensitive technologies have been developed that allow the interrogation of DNA methylation patterns from a small number of cells. The use of these technologies has greatly improved our knowledge of DNA methylation dynamics and heterogeneity in embryos and in specific tissues. Combined with genetic analyses, it is increasingly apparent that regulation of DNA methylation erasure and (re-)establishment varies considerably between different developmental stages. In this Review, we discuss the mechanisms and functions of DNA methylation and demethylation in both mice and humans at CpG-rich promoters, gene bodies and transposable elements. We highlight the dynamic erasure and re-establishment of DNA methylation in embryonic, germline and somatic cell development. Finally, we provide insights into DNA methylation gained from studying genetic diseases.
Abstract
While footprinting analysis of ATAC-seq data can theoretically enable investigation of transcription factor (TF) binding, the lack of a computational tool able to conduct different levels of ...footprinting analysis has so-far hindered the widespread application of this method. Here we present TOBIAS, a comprehensive, accurate, and fast footprinting framework enabling genome-wide investigation of TF binding dynamics for hundreds of TFs simultaneously. We validate TOBIAS using paired ATAC-seq and ChIP-seq data, and find that TOBIAS outperforms existing methods for bias correction and footprinting. As a proof-of-concept, we illustrate how TOBIAS can unveil complex TF dynamics during zygotic genome activation in both humans and mice, and propose how zygotic Dux activates cascades of TFs, binds to repeat elements and induces expression of novel genetic elements.
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract in chronic or recurrent remission phase and is classified as Crohn's disease (CD) and ...ulcerative colitis (UC). IBD is a multifactorial disease that results from genetic and environmental factors, immunological disorders, and gut microbiota dysregulation called dysbiosis. Recently, the number of patients with IBD in Japan has been increasing. This review describes studies of T cells, such as type 1 helper T (Th1) and type 1 cytotoxic T (Tc1) cells, and cytokines, such as IL‐17 and IL‐21, as representatives of mucosal immunity in IBD. Th1 cells and Tc1 cells are involved in Peyer's patches of CD. IL‐12 significantly reduced the production of IL‐17 but significantly increased in that of IFN‐γ, and IL‐21 reduced IL‐17 production. It also describes genetic analysis studies on the cause of very early‐onset IBD (VEO‐IBD). Furthermore, 11.6% of patients with VEO‐IBD presented with monogenic IBD in Japan. Genetic analysis for patients with VEO‐IBD and suspected monogenic IBD was investigated. XIAP and heterozygous SLCO2A1 were detected owing to the result of functional confirmation, and several candidate genes were detected. Cytokine analysis and genetic analysis studies have revealed several pathophysiologies of IBD. Clinical and basic studies on mucosal immunity as well as immunological and genetic analyses are currently ongoing and are anticipated to provide an elaborate understanding of the pathophysiology of IBD.
Cancer metabolism: looking forward Martínez-Reyes, Inmaculada; Chandel, Navdeep S
Nature reviews. Cancer,
10/2021, Letnik:
21, Številka:
10
Journal Article
Recenzirano
Tumour initiation and progression requires the metabolic reprogramming of cancer cells. Cancer cells autonomously alter their flux through various metabolic pathways in order to meet the increased ...bioenergetic and biosynthetic demand as well as mitigate oxidative stress required for cancer cell proliferation and survival. Cancer driver mutations coupled with environmental nutrient availability control flux through these metabolic pathways. Metabolites, when aberrantly accumulated, can also promote tumorigenesis. The development and application of new technologies over the last few decades has not only revealed the heterogeneity and plasticity of tumours but also allowed us to uncover new metabolic pathways involved in supporting tumour growth. The tumour microenvironment (TME), which can be depleted of certain nutrients, forces cancer cells to adapt by inducing nutrient scavenging mechanisms to sustain cancer cell proliferation. There is growing appreciation that the metabolism of cell types other than cancer cells within the TME, including endothelial cells, fibroblasts and immune cells, can modulate tumour progression. Because metastases are a major cause of death of patients with cancer, efforts are underway to understand how metabolism is harnessed by metastatic cells. Additionally, there is a new interest in exploiting cancer genetic analysis for patient stratification and/or dietary interventions in combination with therapies that target metabolism. In this Perspective, we highlight these main themes that are currently under investigation in the context of in vivo tumour metabolism, specifically emphasizing questions that remain unanswered.
The Prevalence of Wilson’s Disease: An Update Sandahl, Thomas Damgaard; Laursen, Tea Lund; Munk, Ditte Emilie ...
Hepatology (Baltimore, Md.),
February 2020, Letnik:
71, Številka:
2
Journal Article
Recenzirano
Background and Aims
In 1984, Scheinberg and Sternlieb estimated the prevalence of Wilson’s disease to be 1:30,000 based on the limited available data. This suggested a large number of overlooked ...cases with potentially fatal consequences. The “Scheinberg‐Sternlieb Estimate” is still widely used, although more recent clinical and genetic studies of higher quality are now available. In the present study, we included these data to update the prevalence estimate.
Approach and Results
A MEDLINE Ovid, Science Citation Index Expanded, and PubMed systematic search for all relevant studies on the prevalence of Wilson’s disease was conducted. In total, 59 studies (50 clinical and 9 population‐based genetic) were included in the final analysis. We identified 4 recent clinical studies based on nationwide databases of high quality, providing prevalence estimates from 1:29,000 to 1:40,000. Higher frequency populations do exist because of frequent first‐cousin marriages and/or a higher mutation frequency. When calculating prevalence from the incidence related to number of births, estimates were 1:40,000‐1:50,000. Clinical screening studies, including examination for Kayser‐Fleischer rings or ceruloplasmin, did not improve these estimates because of insufficient sample size or selection biases. Population‐based genetic studies in US and UK populations were not in disagreement with the clinically based estimates. At the same time, studies from France and Sardinia suggested that the genetic prevalence may be 3‐4 times higher than the clinical disease prevalence. This raises the question whether the penetrance is indeed 100% as generally assumed.
Conclusions
The original prevalence estimate from 1984 of 1:30,000‐1:50,000 still appears valid, at least for the United States, Europe, and Asia. In some population‐based studies, the genetic prevalence was 3‐4 times higher than clinically based estimates. The question of penetrance needs further evaluation.
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