Age-Associated Hyper-Methylated Regions in the Human Brain Overlap with Bivalent Chromatin Domains

PMCID: PMC3454416This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

“Epic-Genetics”: An exploration of preservice helping professionals’ (mis)understanding of epigenetic influences on human development

Mental health researchers emphasize the importance of practitioner understanding of biology-environment interplay. Accordingly, our goal of the study described in this article was to understand students’ preconceptions and misconceptions about biological and environmental influences on development through investigating their conceptions of epigenetics. Using a short-term longitudinal design, we explored preservice helping professionals’ conceptions and misconceptions pertaining to epigenetics within the framework of a graduate level human development course. Baseline knowledge about epigenetics was low. Students developed multiple misconceptions about epigenetics and how the phenomenon relates to biological and environmental influences on human development. Students reported feeling highly efficacious for detecting and resolving misconceptions related to biology-environment interactions but varied in their perceptions of interest for learning about the content. Findings support the use of open-ended questions to detect misconceptions about epigenetics and are discussed in light of how to teach students about this phenomenon. Overall, this research speaks to the importance of understanding the misconceptions students believe and instructional strategies that may assist in correcting them

Genomic organization of duplicated short wave-sensitive and long wave-sensitive opsin genes in the green swordtail, Xiphophorus helleri

<p>Abstract</p> <p>Background</p> <p>Long wave-sensitive (<it>LWS</it>) opsin genes have undergone multiple lineage-specific duplication events throughout the evolution of teleost fishes. <it>LWS </it>repertoire expansions in live-bearing fishes (family Poeciliidae) have equipped multiple species in this family with up to four <it>LWS </it>genes. Given that color vision, especially attraction to orange male coloration, is important to mate choice within poeciliids, <it>LWS </it>opsins have been proposed as candidate genes driving sexual selection in this family. To date the genomic organization of these genes has not been described in the family Poeciliidae, and little is known about the mechanisms regulating the expression of <it>LWS </it>opsins in any teleost.</p> <p>Results</p> <p>Two BAC clones containing the complete genomic repertoire of <it>LWS </it>opsin genes in the green swordtail fish, <it>Xiphophorus helleri</it>, were identified and sequenced. Three of the four <it>LWS </it>loci identified here were linked in a tandem array downstream of two tightly linked short wave-sensitive 2 (<it>SWS2</it>) opsin genes. The fourth <it>LWS </it>opsin gene, containing only a single intron, was not linked to the other three and is the product of a retrotransposition event. Genomic and phylogenetic results demonstrate that the <it>LWS </it>genes described here share a common evolutionary origin with those previously characterized in other poeciliids. Using qualitative RT-PCR and MSP we showed that each of the <it>LWS </it>and <it>SWS2 </it>opsins, as well as three other cone opsin genes and a single rod opsin gene, were expressed in the eyes of adult female and male <it>X. helleri</it>, contributing to six separate classes of adult retinal cone and rod cells with average λ_maxvalues of 365 nm, 405 nm, 459 nm, 499 nm, 534 nm and 568 nm. Comparative genomic analysis identified two candidate teleost opsin regulatory regions containing putative CRX binding sites and hormone response elements in upstream sequences of <it>LWS </it>gene regions of seven teleost species, including <it>X. helleri</it>.</p> <p>Conclusions</p> <p>We report the first complete genomic description of <it>LWS </it>and <it>SWS2 </it>genes in poeciliids. These data will serve as a reference for future work seeking to understand the relationship between <it>LWS </it>opsin genomic organization, gene expression, gene family evolution, sexual selection and speciation in this fish family.</p

Using citizen science to identify Australia’s least known birds and inform conservation action

Citizen science is a popular approach to biodiversity surveying, whereby data that are collected by volunteer naturalists may help analysts to understand the distribution and abundance of wild organisms. In Australia, birdwatchers have contributed to two major citizen science programs, eBird (run by the Cornell Lab of Ornithology) and Birdata (run by Birdlife Australia), which collectively hold more than 42 million records of wild birds from across the country. However, these records are not evenly distributed across space, time, or taxonomy, with particularly significant variation in the number of records of each species in these datasets. In this paper, we explore this variation and seek to determine which Australian bird species are least known as determined by rates of citizen science survey detections. We achieve this by comparing the rates of survey effort and species detection across each Australian bird species? range, assigning all 581 species to one of the four groups depending on their rates of survey effort and species observation. We classify 56 species into a group considered the most poorly recorded despite extensive survey effort, with Coxen?s Fig Parrot Cyclopsitta coxeni, Letter-winged Kite Elanus scriptus, Night Parrot Pezoporus occidentalis, Buff-breasted Buttonquail Turnix olivii and Red-chested Buttonquail Turnix pyrrhothorax having the very lowest numbers of records. Our analyses provide a framework to identify species that are poorly represented in citizen science datasets. We explore the reasons behind why they may be poorly represented and suggest ways in which targeted approaches may be able to help fill in the gaps.Publisher PDFPeer reviewe

The Effect of Single Nucleotide Polymorphisms from Genome Wide Association Studies in Multiple Sclerosis on Gene Expression

BACKGROUND: Multiple sclerosis (MS) is a complex neurological disorder. Its aetiology involves both environmental and genetic factors. Recent genome-wide association studies have identified a number of single nucleotide polymorphisms (SNPs) associated with susceptibility to (MS). We investigated whether these genetic variations were associated with alteration in gene expression. METHODS/PRINCIPAL FINDINGS: We used a database of mRNA expression and genetic variation derived from immortalised peripheral lymphocytes to investigate polymorphisms associated with MS for correlation with gene expression. Several SNPs were found to be associated with changes in expression: in particular two with HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1, HLA-DRB4 and HLA-DRB5, one with ZFP57, one with CD58, two with IL7 and FAM164A, and one with FAM119B, TSFM and KUB3. We found minimal cross-over with a recent whole genome expression study in MS patients. DISCUSSION: We have shown that many susceptibility loci in MS are associated with changes in gene expression using an unbiased expression database. Several of these findings suggest novel gene candidates underlying the effects of MS-associated genetic variation

Complete Haplotype Sequence of the Human Immunoglobulin Heavy-Chain Variable, Diversity, and Joining Genes and Characterization of Allelic and Copy-Number Variation

The immunoglobulin heavy-chain locus (IGH) encodes variable (IGHV), diversity (IGHD), joining (IGHJ), and constant (IGHC) genes and is responsible for antibody heavy-chain biosynthesis, which is vital to the adaptive immune response. Programmed V-(D)-J somatic rearrangement and the complex duplicated nature of the locus have impeded attempts to reconcile its genomic organization based on traditional B-lymphocyte derived genetic material. As a result, sequence descriptions of germline variation within IGHV are lacking, haplotype inference using traditional linkage disequilibrium methods has been difficult, and the human genome reference assembly is missing several expressed IGHV genes. By using a hydatidiform mole BAC clone resource, we present the most complete haplotype of IGHV, IGHD, and IGHJ gene regions derived from a single chromosome, representing an alternate assembly of ∼1 Mbp of high-quality finished sequence. From this we add 101 kbp of previously uncharacterized sequence, including functional IGHV genes, and characterize four large germline copy-number variants (CNVs). In addition to this germline reference, we identify and characterize eight CNV-containing haplotypes from a panel of nine diploid genomes of diverse ethnic origin, discovering previously unmapped IGHV genes and an additional 121 kbp of insertion sequence. We genotype four of these CNVs by using PCR in 425 individuals from nine human populations. We find that all four are highly polymorphic and show considerable evidence of stratification (Fst = 0.3–0.5), with the greatest differences observed between African and Asian populations. These CNVs exhibit weak linkage disequilibrium with SNPs from two commercial arrays in most of the populations tested

Mechanisms Underlying Metabolic and Neural Defects in Zebrafish and Human Multiple Acyl-CoA Dehydrogenase Deficiency (MADD)

In humans, mutations in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH) lead to MADD/glutaric aciduria type II, an autosomal recessively inherited disorder characterized by a broad spectrum of devastating neurological, systemic and metabolic symptoms. We show that a zebrafish mutant in ETFDH, xavier, and fibroblast cells from MADD patients demonstrate similar mitochondrial and metabolic abnormalities, including reduced oxidative phosphorylation, increased aerobic glycolysis, and upregulation of the PPARG-ERK pathway. This metabolic dysfunction is associated with aberrant neural proliferation in xav, in addition to other neural phenotypes and paralysis. Strikingly, a PPARG antagonist attenuates aberrant neural proliferation and alleviates paralysis in xav, while PPARG agonists increase neural proliferation in wild type embryos. These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention

Gut Microbiota Composition Modulates the Magnitude and Quality of Germinal Centers during Plasmodium Infections

Gut microbiota composition is associated with human and rodent Plasmodium infections, yet the mechanism by which gut microbiota affects the severity of malaria remains unknown. Humoral immunity is critical in mediating the clearance of Plasmodium blood stage infections, prompting the hypothesis that mice with gut microbiota-dependent decreases in parasite burden exhibit better germinal center (GC) responses. In support of this hypothesis, mice with a low parasite burden exhibit increases in GC B cell numbers and parasite-specific antibody titers, as well as better maintenance of GC structures and a more targeted, qualitatively different antibody response. This enhanced humoral immunity affects memory, as mice with a low parasite burden exhibit robust protection against challenge with a heterologous, lethal Plasmodium species. These results demonstrate that gut microbiota composition influences the biology of spleen GCs as well as the titer and repertoire of parasite-specific antibodies, identifying potential approaches to develop optimal treatments for malaria

Phosphatidylinositol synthase is required for lens structural integrity and photoreceptor cell survival in the zebrafish eye

The zebrafish lens opaque (lop) mutant was previously isolated in a genetic screen and shown to lack rod and cone photoreceptors and exhibit lens opacity, or cataract, at 7 days post-fertilization (dpf). In this manuscript, we provide four different lines of evidence demonstrating that the lop phenotype results from a defect in the cdipt (phosphatidylinositol (PI) synthase; CDP-diacylglycerol--inositol 3-phosphatidyltransferase) gene. First, DNA sequence analysis revealed that the lop mutant contained a missense mutation in the lop open reading frame, which yields a nonconservative amino acid substitution (Ser-111-Cys) within the PI synthase catalytic domain. Second, morpholino-mediated knockdown of the cdipt-encoded PI synthase protein phenocopied the cdiptlop/lop mutant, with abnormal lens epithelial and secondary fiber cell morphologies and reduced numbers of photoreceptors. Third, microinjection of in vitro transcribed, wild-type cdipt mRNA into 1-4 cell stage cdiptlop/lop embryos significantly reduced the percentage of larvae displaying lens opacity at 7 dpf. Fourth, a cdipt retroviral-insertion allele, cdipthi559, exhibited similar lens and retinal abnormalities and failed to complement the cdiptlop mutant phenotype

Identification of Subject-Specific Immunoglobulin Alleles From Expressed Repertoire Sequencing Data

The adaptive immune receptor repertoire (AIRR) contains information on an individuals' immune past, present and potential in the form of the evolving sequences that encode the B cell receptor (BCR) repertoire. AIRR sequencing (AIRR-seq) studies rely on databases of known BCR germline variable (V), diversity (D), and joining (J) genes to detect somatic mutations in AIRR-seq data via comparison to the best-aligning database alleles. However, it has been shown that these databases are far from complete, leading to systematic misidentification of mutated positions in subsets of sample sequences. We previously presented TIgGER, a computational method to identify subject-specific V gene genotypes, including the presence of novel V gene alleles, directly from AIRR-seq data. However, the original algorithm was unable to detect alleles that differed by more than 5 single nucleotide polymorphisms (SNPs) from a database allele. Here we present and apply an improved version of the TIgGER algorithm which can detect alleles that differ by any number of SNPs from the nearest database allele, and can construct subject-specific genotypes with minimal prior information. TIgGER predictions are validated both computationally (using a leave-one-out strategy) and experimentally (using genomic sequencing), resulting in the addition of three new immunoglobulin heavy chain V (IGHV) gene alleles to the IMGT repertoire. Finally, we develop a Bayesian strategy to provide a confidence estimate associated with genotype calls. All together, these methods allow for much higher accuracy in germline allele assignment, an essential step in AIRR-seq studies