BICOSS: Bayesian iterative conditional stochastic search for GWAS.

Background: Single marker analysis (SMA) with linear mixed models for genome wide association studies has uncovered the contribution of genetic variants to many observed phenotypes. However, SMA has weak false discovery control. In addition, when a few variants have large effect sizes, SMA has low statistical power to detect small and medium effect sizes, leading to low recall of true causal single nucleotide polymorphisms (SNPs).

Genomic imbalance modulates transposable element expression in maize.

Genomic imbalance refers to the more severe phenotypic consequences of changing part of a chromosome compared with the whole genome set. Previous genome imbalance studies in maize have identified prevalent inverse modulation of genes on the unvaried chromosomes (trans) with both the addition or subtraction of chromosome arms. Transposable elements (TEs) comprise a substantial fraction of the genome, and their reaction to genomic imbalance is therefore of interest.

Dosage-sensitive miRNAs trigger modulation of gene expression during genomic imbalance in maize.

The genomic imbalance caused by varying the dosage of individual chromosomes or chromosomal segments (aneuploidy) has more detrimental effects than altering the dosage of complete chromosome sets (ploidy). Previous analysis of maize (Zea mays) aneuploids revealed global modulation of gene expression both on the varied chromosome (cis) and the remainder of the genome (trans). However, little is known regarding the role of microRNAs (miRNAs) under genomic imbalance.

Effect of aneuploidy of a non-essential chromosome on gene expression in maize.

The non-essential supernumerary maize (Zea mays) B chromosome (B) has recently been shown to contain active genes and to be capable of impacting gene expression of the A chromosomes. However, the effect of the B chromosome on gene expression is still unclear. In addition, it is unknown whether the accumulation of the B chromosome has a cumulative effect on gene expression.

Sequence of the supernumerary B chromosome of maize provides insight into its drive mechanism and evolution.

B chromosomes are enigmatic elements in thousands of plant and animal genomes that persist in populations despite being nonessential. They circumvent the laws of Mendelian inheritance but the molecular mechanisms underlying this behavior remain unknown. Here we present the sequence, annotation, and analysis of the maize B chromosome providing insight into its drive mechanism.

Genomic imbalance determines positive and negative modulation of gene expression in diploid maize.

Genomic imbalance caused by changing the dosage of individual chromosomes (aneuploidy) has a more detrimental effect than varying the dosage of complete sets of chromosomes (ploidy). We examined the impact of both increased and decreased dosage of 15 distal and 1 interstitial chromosomal regions via RNA-seq of maize (Zea mays) mature leaf tissue to reveal new aspects of genomic imbalance. The results indicate that significant changes in gene expression in aneuploids occur both on the varied chromosome (cis) and the remainder of the genome (trans), with a wider spread of modulation compared with the whole-ploidy series of haploid to tetraploid.

Predominantly inverse modulation of gene expression in genomically unbalanced disomic haploid maize.

The phenotypic consequences of the addition or subtraction of part of a chromosome is more severe than changing the dosage of the whole genome. By crossing diploid trisomies to a haploid inducer, we identified 17 distal segmental haploid disomies that cover ∼80% of the maize genome. Disomic haploids provide a level of genomic imbalance that is not ordinarily achievable in multicellular eukaryotes, allowing the impact to be stronger and more easily studied.

An empirical bayesian approach for testing gene expression fold change and its application in detecting global dosage effects.

We are motivated by biological studies intended to understand global gene expression fold change. Biologists have generally adopted a fixed cutoff to determine the significance of fold changes in gene expression studies (e.g.

Magnitude of modulation of gene expression in aneuploid maize depends on the extent of genomic imbalance.

Aneuploidy has profound effects on an organism, typically more so than polyploidy, and the basis of this contrast is not fully understood. A dosage series of the maize long arm of chromosome 1 (1L) was used to compare relative global gene expression in different types and degrees of aneuploidy to gain insights into how the magnitude of genomic imbalance as well as hypoploidy affects global gene expression. While previously available methods require a selective examination of specific genes, RNA sequencing provides a whole-genome view of gene expression in aneuploids.

The Gene Balance Hypothesis: Epigenetics and Dosage Effects in Plants.

Dosage effects in plants are caused by changes in the copy number of chromosomes, segments of chromosomes, or multiples of individual genes. Genes often exhibit a dosage effect in which the amount of product is closely correlated with the number of copies present. However, when larger segments of chromosomes are varied, there are trans-acting effects across the genome that are unleashed that modulate gene expression in cascading effects.

Conditions of embryo culture from days 5 to 7 of development alter the DNA methylome of the bovine fetus at day 86 of gestation.

Purpose: We tested whether in vitro production (IVP) causes changes in DNA methylation in fetal liver and skeletal muscle and if exposure of cultured embryos to colony-stimulating factor 2 (CSF2) alters DNA methylation.

Methods: Female fetuses were produced by artificial insemination or transfer of an IVP embryo. Embryos were treated from days 5 to 7 after fertilization with CSF2 or vehicle.

Modeling allele-specific expression at the gene and SNP levels simultaneously by a Bayesian logistic mixed regression model.

Background: High-throughput sequencing experiments, which can determine allele origins, have been used to assess genome-wide allele-specific expression. Despite the amount of data generated from high-throughput experiments, statistical methods are often too simplistic to understand the complexity of gene expression. Specifically, existing methods do not test allele-specific expression (ASE) of a gene as a whole and variation in ASE within a gene across exons separately and simultaneously.

Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome.

The use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observed global misregulation of transcripts in bovine foetuses with LOS.

Differential gene expression in response to eCry3.1Ab ingestion in an unselected and eCry3.1Ab-selected western corn rootworm (Diabrotica virgifera virgifera LeConte) population.

Diabrotica virgifera virgifera LeConte, the western corn rootworm (WCR) is one of the most destructive pests in the U.S. Corn Belt.

Lean maternal hyperglycemia alters offspring lipid metabolism and susceptibility to diet-induced obesity in mice†.

We previously developed a model of gestational diabetes mellitus (GDM) in which dams exhibit glucose intolerance, insulin resistance, and reduced insulin response to glucose challenge only during pregnancy, without accompanying obesity. Here, we aimed to determine how lean gestational glucose intolerance affects offspring risk of metabolic dysfunction. One cohort of offspring was sacrificed at 19 weeks, and one at 31 weeks, with half of the second cohort placed on a high-fat, high-sucrose diet (HFHS) at 23 weeks.

The effects of biological aging on global DNA methylation, histone modification, and epigenetic modifiers in the mouse germinal vesicle stage oocyte.

A cultural trend in developed countries is favoring a delay in maternal age at first childbirth. In mammals fertility and chronological age show an inverse correlation. Oocyte quality is a contributing factor to this multifactorial phenomenon that may be influenced by age-related changes in the oocyte epigenome.

A Bayesian hidden Markov model for detecting differentially methylated regions.

Alterations in DNA methylation have been linked to the development and progression of many diseases. The bisulfite sequencing technique presents methylation profiles at base resolution. Count data on methylated and unmethylated reads provide information on the methylation level at each CpG site.

Global impacts of chromosomal imbalance on gene expression in and other taxa.

Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids, triploids, and tetraploids of was studied. The trisomies displayed a greater spread of expression modulation than the ploidy series.

Detecting differentially expressed genes for syndromes by considering change in mean and dispersion simultaneously.

Background: Using next-generation sequencing technology to measure gene expression, an empirically intriguing question concerns the identification of differentially expressed genes across treatment groups. Existing methods aim to identify genes whose mean expressions differ among treatment groups by assuming equal dispersion across all groups. For syndromes, however, various combinations of gene expression alterations can result in the same disease, leading to greater heteroscedasticity in the biological replicates in the disease group compared to the normal group.

Porcine Fetal-Derived Fibroblasts Alter Gene Expression and Mitochondria to Compensate for Hypoxic Stress During Culture.

The Warburg effect is characterized by decreased mitochondrial oxidative phosphorylation and increased glycolytic flux in adequate oxygen. The preimplantation embryo has been described to have characteristics of the Warburg effect, including similar changes in gene expression and mitochondria, which are more rudimentary in appearance. We hypothesized hypoxia would facilitate anaerobic glycolysis in fibroblasts thereby promoting gene expression and media metabolite production reflecting the Warburg effect hallmarks in early embryos.

Glutamine supplementation enhances development of in vitro-produced porcine embryos and increases leucine consumption from the medium.

Improper composition of culture medium contributes to reduced viability of in vitro-produced embryos. Glutamine (Gln) is a crucial amino acid for preimplantation embryos as it supports proliferation and is involved in many different biosynthetic pathways. Previous transcriptional profiling revealed several upregulated genes related to Gln transport and metabolism in in vitro-produced porcine blastocysts compared to in vivo-produced counterparts, indicating a potential deficiency in the culture medium.

Pharmacologic Reprogramming Designed to Induce a Warburg Effect in Porcine Fetal Fibroblasts Alters Gene Expression and Quantities of Metabolites from Conditioned Media Without Increased Cell Proliferation.

The Warburg effect is a metabolic phenomenon characterized by increased glycolytic activity, decreased mitochondrial oxidative phosphorylation, and the production of lactate. This metabolic phenotype is characterized in rapidly proliferative cell types such as cancerous cells and embryonic stem cells. We hypothesized that a Warburg-like metabolism could be achieved in other cell types by treatment with pharmacological agents, which might, in turn, facilitate nuclear reprogramming.

Global misregulation of genes largely uncoupled to DNA methylome epimutations characterizes a congenital overgrowth syndrome.

Assisted reproductive therapies (ART) have become increasingly common worldwide and numerous retrospective studies have indicated that ART-conceived children are more likely to develop the overgrowth syndrome Beckwith-Wiedemann (BWS). In bovine, the use of ART can induce a similar overgrowth condition, which is referred to as large offspring syndrome (LOS). Both BWS and LOS involve misregulation of imprinted genes.

Global assessment of imprinted gene expression in the bovine conceptus by next generation sequencing.

Genomic imprinting is an epigenetic mechanism that leads to parental-allele-specific gene expression. Approximately 150 imprinted genes have been identified in humans and mice but less than 30 have been described as imprinted in cattle. For the purpose of de novo identification of imprinted genes in bovine, we determined global monoallelic gene expression in brain, skeletal muscle, liver, kidney and placenta of day ∼105 Bos taurus indicus × Bos taurus taurus F1 conceptuses using RNA sequencing.

Maternal Hyperleptinemia Is Associated with Male Offspring's Altered Vascular Function and Structure in Mice.

Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Leprdb/+ dams were compared to genotype matched offspring of WT-control dams.