The detection of a strong episignature for Chung–Jansen syndrome, partially overlapping with Börjeson–Forssman–Lehmann and White–Kernohan syndromes

Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It is caused by pathogenic variants in the PHIP gene that encodes for the Pleckstrin homology domain-interacting protein, which is part of an epigenetic modifier protein complex. Therefore, we hypothesized that PHIP haploinsufficiency may impact genome-wide DNA methylation (DNAm). We assessed the DNAm profiles of affected individuals with pathogenic and likely pathogenic PHIP variants with Infinium Methylation EPIC arrays and report a specific and sensitive DNAm episignature biomarker for Chung–Jansen syndrome. In addition, we observed similarities between the methylation profile of Chung–Jansen syndrome and that of functionally related and clinically partially overlapping genetic disorders, White–Kernohan syndrome (caused by variants in DDB1 gene) and Börjeson–Forssman–Lehmann syndrome (caused by variants in PHF6 gene). Based on these observations we also proceeded to develop a common episignature biomarker for these disorders. These newly defined episignatures can be used as part of a multiclass episignature classifier for screening of affected individuals with rare disorders and interpretation of genetic variants of unknown clinical significance, and provide further insights into the common molecular pathophysiology of the clinically-related Chung–Jansen, Börjeson–Forssman–Lehmann and White–Kernohan syndromes.</p

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±

Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based Nutritional Intervention: The Food4Me Study

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI), waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Comparative performance and economic appraisal of Holstein-Friesian, Jersey and Jersey×Holstein-Friesian cows under seasonal pasture-based management

peer-reviewedThe objective of this study was to provide comparative performance data for Holstein- Friesian (HF), Jersey (J) and Jersey×Holstein-Friesian (F1) cows under a seasonal pasture-based management system and to simulate the effect of cow breed on farm profitability. Data for a total of 329 lactations, from 162 (65 HF, 48 J and 49 F1) cows, were available. Milk yield was highest for HF, intermediate for F1 and lowest for J, while milk fat and protein concentrations were highest for J, intermediate for F1 and lowest for HF. Yield of fat plus protein was highest for F1, intermediate for HF and lowest for J. Mean bodyweight was 523, 387 and 466 kg for HF, J and F1, respectively. Body condition score was greater for the J and F1 compared to HF. Reproductive efficiency was similar for the HF and J but superior for the F1. The Moorepark Dairy Systems Model was used to simulate a 40 ha farm integrating biological data for each breed group. Milk output was highest for systems based on HF cows. Total sales of milk solids and, consequently, milk receipts were higher with J and F1 compared to HF. Total costs were lowest with F1 cows, intermediate with HF and highest with J. Overall farm profitability was highest with F1 cows, intermediate with HF and lowest with J. Sensitivity analysis of milk price, fat to protein price ratio and differences in cost of replacement heifers showed no re-ranking of the breed groups for farm profit.Department of Agriculture, Food and the Marine, Ireland - Research Stimulus Fund (RSF-06-353)

On Super (a, d)-H-Antimagic Total Covering of Star Related Graphs

Let G = (V (G),E(G)) be a simple graph and H be a subgraph of G. G admits an H-covering, if every edge in E(G) belongs to at least one subgraph of G that is isomorphic to H. An (a, d)-H-antimagic total labeling of G is a bijection λ: V (G) ∪ E(G) → {1, 2, 3, . . . , |V (G)| + |E(G)|} such that for all subgraphs H′ isomorphic to H, the H′ weight

On Super (a,d)(a, d)-HH-Antimagic Total Covering of Star Related Graphs

Let $G = (V (G), E (G))$ be a simple graph and $H$ be a subgraph of $G$. $G$ admits an $H$-covering, if every edge in $E(G)$ belongs to at least one subgraph of $G$ that is isomorphic to $H$. An $(a, d)$-$H$-antimagic total labeling of $G$ is a bijection $\lambda : V (G) \cup E(G) \rightarrow {1, 2, 3, . . ., |V (G)| + |E(G)|}$ such that for all subgraphs H^' isomorphic to $H$, the $H^′$ weights wt(H^') = \sum_{v \in V (H^') } \lambda (v) + \sum_{e \in E(H^')} \lambda (e) constitute an arithmetic progression $a$, $a+d$, $a+2d$, . . ., $a+(n−1)d$ where $a$ and $d$ are positive integers and $n$ is the number of subgraphs of $G$ isomorphic to $H$. Additionally, the labeling $\lambda$ is called a super $(a, d)$-$H$-antimagic total labeling if $\lambda (V (G)) = {1, 2, 3, . . ., |V (G)|}$. In this paper we study super $(a, d)-H$-antimagic total labelings of star related graphs $G_u[S_n]$ and caterpillars