Stonegriffin1265

Bariatric surgery results in sustained weight loss and improvement in glucose homeostasis. However, the lack of accessible non-invasive tools to examine molecular alterations occurring in the pancreas limits our understanding of the causes and recovery of glucose homeostasis. Here, we describe the use of a circulating cell free mRNA (cfmRNA) based multiplex qPCR assay to selectively amplify and quantify circulating pancreatic specific transcripts levels within plasma. We applied this assay to a cohort of 58 plasma samples consisting of 10 patients that tracks multiple time points including pre and post-bariatric surgery. In our targeted multiplex screen of 14 selected pancreatic specific circulating transcripts, we identified 13 pancreatic specific transcripts that can be amplified from plasma. Furthermore, when quantifying the amplicons obtained in the short-term post-surgery (2 weeks-1 month) and long-term (3-12 months), we observed a consistent reduction of circulating GCG transcripts during short term post-surgery. Across the cohort, GCG cfmRNA levels correlated significantly with common metrics of improvement following bariatric surgery such as haemoglobin A1c levels (R -0.41, p-value 0.0039) and percentage of excess weight loss (R 0.29, p-value 0.046).The phenotype of mice carrying the Gata1 low mutation that decreases expression of Gata1 in erythroid cells and megakaryocytes, includes anemia, thrombocytopenia, hematopoietic failure in bone marrow and development of extramedullary hematopoiesis in spleen. Cyclopamine datasheet With age, these mice develop myelofibrosis, a disease sustained by alterations in stem/progenitor cells and megakaryocytes. This study analyzed the capacity of hGATA1 driven by a μLCR/β-globin promoter to rescue the phenotype induced by the Gata1 low mutation in mice. Double hGATA1/Gata1 low/0 mice were viable at birth with hematocrits greater than those of their Gata1 low/0 littermates but platelet counts remained lower than normal. hGATA1 mRNA was expressed by progenitor and erythroid cells from double mutant mice but not by megakaryocytes analyzed in parallel. The erythroid cells from hGATA1/Gata1 low/0 mice expressed greater levels of GATA1 protein and of α- and β-globin mRNA than cells from Gata1 low/0 littermates and a reduced number of them was in t progenitors and erythroid cells but not in megakaryocytes rescuing the erythroid but not the megakaryocyte defect induced by the Gata1 low/0 mutation.Plasma total homocysteine (tHCY) is a known risk factor of a wide range of complex diseases. No genome scans for tHCY have been conducted in East Asian populations. Here, we conducted an exome-wide association study (ExWAS) for tHCY in 5,175 individuals of Chinese Han origin, followed by a replication study in 668 Chinese individuals. The ExWAS identified two loci, 1p36.22 (lead single-nucleotide polymorphism (SNP) rs1801133, MTHFR C677T) and 16q24.3 (rs1126464, DPEP1), showing exome-wide significant association with tHCY (p less then 5E-7); and both loci have been previously associated with tHCY in non-East Asian populations. Both SNPs were replicated in the replication study (p less then 0.05). Conditioning on the genotype of C677T and rs1126464, we identified a novel East Asian-specific missense variant rs138189536 (C136T) of MTHFR (p = 6.53E-10), which was also significant in the replication study (p = 9.8E-3). The C136T and C677T variants affect tHCY in a compound heterozygote manner, where compound heterozygote and homozygote genotype carriers had on average 43.4% increased tHCY than had other genotypes. The frequency of the homozygote C677T genotype showed an inverse-U-shaped geospatial pattern globally with a pronounced frequency in northern China, which coincided with the high prevalence of hyperhomocysteinemia (HHCY) in northern China. A logistic regression model of HHCY status considering sex, age, and the genotypes of the three identified variants reached an area under the receiver operating characteristic curve (AUC) value of 0.74 in an independent validation cohort. These genetic observations provide new insights into the presence of multiple causal mutations at the MTHFR locus, highlight the role of genetics in HHCY epidemiology among different populations, and provide candidate loci for future functional studies.Genomic prediction has been widely used in multiple areas and various genomic prediction methods have been developed. The majority of these methods, however, focus on statistical properties and ignore the abundant useful biological information like genome annotation or previously discovered causal variants. Therefore, to improve prediction performance, several methods have been developed to incorporate biological information into genomic prediction, mostly in single-trait analysis. A commonly used method to incorporate biological information is allocating molecular markers into different classes based on the biological information and assigning separate priors to molecular markers in different classes. It has been shown that such methods can achieve higher prediction accuracy than conventional methods in some circumstances. However, these methods mainly focus on single-trait analysis, and available priors of these methods are limited. Thus, in both single-trait and multiple-trait analysis, we propose the multi-class Bayesian Alphabet methods, in which multiple Bayesian Alphabet priors, including RR-BLUP, BayesA, BayesB, BayesCΠ, and Bayesian LASSO, can be used for markers allocated to different classes. The superior performance of the multi-class Bayesian Alphabet in genomic prediction is demonstrated using both real and simulated data. The software tool JWAS offers open-source routines to perform these analyses.

Tyrosinase-positive oculocutaneous albinism (OCA, type II, OCA2) is an autosomal recessive genetic disease in which the biosynthesis of melanin decreases in the skin, hair, and eyes. OCA2 disease is caused by mutations in

gene. The gene product plays a role in regulating the pH of melanosomes. Up to now, hundreds of

mutations have been reported and novel variants are still being discovered.

In this study, we reviewed the records of OCA2 patients who had conducted albinism genetic testing, and then analyzed the clinical and genetic information of 28 OCA2 patients who had been genetically diagnosed by using Sanger sequencing and next-generation sequencing.

In this study, we reported 31 variants screened from 28 Chinese OCA2 families, and characterized the detailed molecular and clinical presentations. There were 12 novel variants among all detected variants, including 3 missense variants (p.G393V, p.T482A, and p.R720P), 4 frameshift variants (p.R53Gfs

49, p.N279Kfs

17, p.I469Lfs

4, p.I655Nfs

12), 2 splicing variants (c.1637-2A > G, c.1951 + 1G > C), 2 stopgain variants (p.L278X, p.W652X) and 1 insertion variants (p.P315LinsT). One potential cluster of missense variants was implicated indicating the important roles of the underlying domains in OCA2 pathogenesis.

Our results were beneficial for diagnosis and precision clinical management for

-related disorder, and this study expanded the mutation spectrum of oculocutaneous albinism.

Our results were beneficial for diagnosis and precision clinical management for OCA2-related disorder, and this study expanded the mutation spectrum of oculocutaneous albinism.Host genetic variants can determine their susceptibility to COVID-19 infection and severity as noted in a recent Genome-wide Association Study (GWAS). Given the prominent genetic differences in Indian sub-populations as well as differential prevalence of COVID-19, here, we compute genetic risk scores in diverse Indian sub-populations that may predict differences in the severity of COVID-19 outcomes. We utilized the top 100 most significantly associated single-nucleotide polymorphisms (SNPs) from a GWAS by Pairo-Castineira et al. determining the genetic susceptibility to severe COVID-19 infection, to compute population-wise polygenic risk scores (PRS) for populations represented in the Indian Genome Variation Consortium (IGVC) database. Using a generalized linear model accounting for confounding variables, we found that median PRS was significantly associated (p less then 2 x 10-16) with COVID-19 mortality in each district corresponding to the population studied and had the largest effect on mortality (regression coefficient = 10.25). As a control we repeated our analysis on randomly selected 100 non-associated SNPs several times and did not find significant association. Therefore, we conclude that genetic susceptibility may play a major role in determining the differences in COVID-19 outcomes and mortality across the Indian sub-continent. We suggest that combining PRS with other observed risk-factors in a Bayesian framework may provide a better prediction model for ascertaining high COVID-19 risk groups and to design more effective public health resource allocation and vaccine distribution schemes.The Duroc × (Landrace × Yorkshire) hybrid pigs (DLY) are the most popular commercial pigs, providing consumers with the largest source of pork. In order to gain more insights into the genetic architecture of economically important traits in pigs, we performed a genome-wide association study (GWAS) using the GeneSeek Porcine 50 K SNP Chip to map the genetic markers and genes associated with body conformation traits (BCT) in 311 DLY pigs. The quantitative traits analyzed included body weight (BW), carcass length (CL), body length (BL), body height (BH), and body mass index (BMI). BMI was defined as BMICL, BMIBL, and BMIBH, respectively, based on CL, BL, and BH phenotypic data. We identified 82 SNPs for the seven traits by GEMMA-based and FarmCPU-based GWASs. Both methods detected two quantitative trait loci (QTL) on SSC8 and SSC17 for body conformation traits. Several candidate genes (such as TNFAIP3, KDM4C, HSPG2, BMP2, PLCB4, and GRM5) were found to be associated with body weight and body conformation traits in pigs. Notably, the BMP2 gene had pleiotropic effects on CL, BL, BH, BMICL, and BMIBL and is proposed as a strong candidate gene for body size due to its involvement in growth and bone development. Furthermore, gene set enrichment analysis indicated that most of the pathway terms are associated with regulation of cell growth, negative regulation of cell population proliferation, and chondrocyte differentiation. We anticipate that these results further advance our understanding of the genetic architecture of body conformation traits in the popular commercial DLY pigs and provide new insights into the genetic architecture of BMI in pigs.In temperate ecosystems, elevated temperatures, and drought occur especially during spring and summer, which are crucial periods for flowering, pollination, and reproduction of a majority of temperate plants. While many mechanisms may underlie pollinator decline in the wake of climate change, the interactive effects of temperature and water stress on the quantity and quality of floral nectar and pollen resources remain poorly studied. We investigated the impact of temperature rise (+3 and +6°C) and water stress (soil humidity lower than 15%) on the floral resources produced by the bee-pollinated species Borago officinalis. Nectar volume decreased with both temperature rise and water stress (6.1 ± 0.5 μl per flower under control conditions, 0.8 ± 0.1 μl per flower under high temperature and water stress conditions), resulting in a 60% decrease in the total quantity of nectar sugars (mg) produced per flower. Temperature rise but not water stress also induced a 50% decrease in pollen weight per flower but a 65% increase in pollen polypeptide concentration.