Showing papers in "Briefings in Functional Genomics in 2010"
TL;DR: Genome selection (GS) as discussed by the authors uses all marker data as predictors of performance and consequently delivers more accurate predictions, potentially leading to more rapid and lower cost gains from breeding. But these traits are complex and affected by many genes, each with small effect.
Abstract: We intuitively believe that the dramatic drop in the cost of DNA marker information we have experienced should have immediate benefits in accelerating the delivery of crop varieties with improved yield, quality and biotic and abiotic stress tolerance. But these traits are complex and affected by many genes, each with small effect. Traditional marker-assisted selection has been ineffective for such traits. The introduction of genomic selection (GS), however, has shifted that paradigm. Rather than seeking to identify individual loci significantly associated with a trait, GS uses all marker data as predictors of performance and consequently delivers more accurate predictions. Selection can be based on GS predictions, potentially leading to more rapid and lower cost gains from breeding. The objectives of this article are to review essential aspects of GS and summarize the important take-home messages from recent theoretical, simulation and empirical studies. We then look forward and consider research needs surrounding methodological questions and the implications of GS for long-term selection.
986 citations
TL;DR: Banerjee et al. as mentioned in this paper proposed Restriction-site associated DNA sequencing, a method that samples at reduced complexity across target genomes, promising to deliver high resolution population genomic data-thousands of sequenced markers across many individuals at reasonable costs.
Abstract: Next-generation sequencing technologies are making a substantial impact on many areas of biology, including the analysis of genetic diversity in populations. However, genome-scale population genetic studies have been accessible only to well-funded model systems. Restriction-site associated DNA sequencing, a method that samples at reduced complexity across target genomes, promises to deliver high resolution population genomic data-thousands of sequenced markers across many individuals-for any organism at reasonable costs. It has found application in wild populations and non-traditional study species, and promises to become an important technology for ecological population genomics.
662 citations
TL;DR: The study of proteomics in skeletal muscles allows generating large amounts of scientific knowledge that helps to improve the understanding of myogenesis and muscle growth and to control better meat quality.
Abstract: Proteomics allows studying large numbers of proteins, including their post-translational modifications. Proteomics has been, and still are, used in numerous studies on skeletal muscle. In this article, we focus on its use in the study of livestock muscle development and meat quality. Changes in protein profiles during myogenesis are described in cattle, pigs and fowl using comparative analyses across different ontogenetic stages. This approach allows a better understanding of the key stages of myogenesis and helps identifying processes that are similar or divergent between species. Genetic variability of muscle properties analysed by the study of hypertrophied cattle and sheep are discussed. Biological markers of meat quality, particularly tenderness in cattle, pigs and fowl are presented, including protein modifications during meat ageing in cattle, protein markers of PSE meat in turkeys and of post-mortem muscle metabolism in pigs. Finally, we discuss the interest of proteomics as a tool to understand better biochemical mechanisms underlying the effects of stress during the pre-slaughter period on meat quality traits. In conclusion, the study of proteomics in skeletal muscles allows generating large amounts of scientific knowledge that helps to improve our understanding of myogenesis and muscle growth and to control better meat quality.
156 citations
TL;DR: Association or linkage disequilibrium mapping has become a very popular method for dissecting the genetic basis of complex traits in plants as mentioned in this paper, which can be a relatively detailed mapping resolution and is far less time consuming since no mapping populations need to be generated.
Abstract: Association or linkage disequilibrium mapping has become a very popular method for dissecting the genetic basis of complex traits in plants. The benefits of association mapping, compared with traditional quantitative trait locus mapping, is, for example, a relatively detailed mapping resolution and that it is far less time consuming since no mapping populations need to be generated. The surge of interest in association mapping has been fueled by recent developments in genomics that allows for rapid identification and scoring of genetic markers which has traditionally limited mapping experiments. With the decreasing cost of genotyping future emphasis will likely focus on phenotyping, which can be both costly and time consuming but which is crucial for obtaining reliable results in association mapping studies. In addition, association mapping studies are prone to the identification of false positives, especially if the experimental design is not rigorously controlled. For example, population structure has long been known to induce many false positives and accounting for population structure has become one of the main issues when implementing association mapping in plants. Also, with increasing numbers of genetic markers used, the problem becomes separating true from false positive and this highlights the need for independent validation of identified association. With these caveats in mind, association mapping nevertheless shows great promise for helping us understand the genetic basis of complex traits of both economic and ecological importance.
156 citations
TL;DR: It is argued that understanding spatio-temporal RNA-protein association on a transcriptome level will provide invaluable and unexpected insights into the regulatory codes that define growth, differentiation and disease.
Abstract: Eukaryotic cells express a large variety of ribonucleic acid-(RNA)-binding proteins (RBPs) with diverse affinity and specificity towards target RNAs that play a crucial role in almost every aspect of RNA metabolism. In addition, specific domains in RBPs impart catalytic activity or mediate protein–protein interactions, making RBPs versatile regulators of gene expression. In this review, we elaborate on recent experimental and computational approaches that have increased our understanding of RNA–protein interactions and their role in cellular function. We review aspects of gene expression that are modulated post-transcriptionally by RBPs, namely the stability of polymerase II-derived mRNA transcripts and their rate of translation into proteins. We further highlight the extensive regulatory networks of RBPs that implement a combinatorial control of gene expression. Taking cues from the recent development in the field, we argue that understanding spatio-temporal RNA–protein association on a transcriptome level will provide invaluable and unexpected insights into the regulatory codes that define growth, differentiation and disease.
155 citations
TL;DR: The aim of this review is to highlight the current progress of these ongoing areas of research, which are mandatory for successful development of biomedical pig models that are in demand for understanding human biology in health and disease.
Abstract: Our current knowledge of human biology is often based on studying a wide range of animal species. In particular, for understanding human diseases, the development of adequate animal models is of immediate importance. Although genetic strains and transgenic animal model organisms like fruit fly (Drosophila), zebrafish and rodents are highly informative about the function of single genes and proteins, these organisms do not always closely reflect human biology, and alternative animal models are thus in great demand. The pig is a non-primate mammal that closely resembles man in anatomy, physiology and genetics. Pigs, although not easily kept for laboratory research, are, however, readily available for biomedical research through the large scale industrial production of pigs produced for human consumption. Recent research has facilitated the biological experimentation with pigs, and helped develop the pig into a novel model organism for biomedical research. This toolbox includes the near completion of the pig genome, catalogues of genes and genetic variation in pigs, extensive characterization of pig proteomes and transcriptomes, as well as the development of transgenic disease models. The aim of this review is to highlight the current progress of these ongoing areas of research, which are mandatory for successful development of biomedical pig models that are in demand for understanding human biology in health and disease.
154 citations
TL;DR: Three important points during these earliest reprogramming events are summarized, which are relatively stable maternal chromatin after fertilization, rapid acquisition of specific histone marks by the paternal chromatin during the hours that follow fertilization and rapid remodelling of constitutive heterochromatic marks and modifications in the core of the nucleosome from the first mitotic division.
Abstract: Fertilization of the oocyte by the sperm results in the formation of a totipotent zygote, in which the maternal and paternal chromatin is enclosed in two pronuclei undergoing distinct programmes of transcriptional activation and chromatin remodelling. The highly packaged paternal chromatin delivered by the sperm is decondensed and acquires a number of specific epigenetic marks, but markedly remains devoid of those usually associated with constitutive heterochromatin. During this period the maternal chromatin remains relatively stable except for marks associated with transcription and/or replication such as arginine methylation and H3/H4 acetylation. The embryo then undergoes a series of mitotic divisions without significant additional growth but differentiation, resulting in the formation of a blastocyst containing distinct cell types. The chromatin remodelling events during these stages are likely to be important in establishing the nuclear foundations required for later triggers of differentiation. Overall, we summarize three important points during these earliest reprogramming events: (i) relatively stable maternal chromatin after fertilization, (ii) rapid acquisition of specific histone marks by the paternal chromatin during the hours that follow fertilization and (iii) rapid remodelling of constitutive heterochromatic marks and modifications in the core of the nucleosome from the first mitotic division. These features are likely to be required for the creation of a chromatin environment compatible with cellular reprogramming and plasticity.
127 citations
TL;DR: Novel concepts on the interdependence of histone modifications marks are described and the molecular mechanisms governing this cross-talks are discussed, in particular on the enzymes responsible for setting these marks.
Abstract: Eukaryotic chromatin can be highly dynamic and can continuously exchange between an open transcriptionally active conformation and a compacted silenced one. Post-translational modifications of histones have a pivotal role in regulating chromatin states, thus influencing all chromatin dependent processes. Methylation is currently one of the best characterized histone modification and occurs on arginine and lysine residues. Histone methylation can regulate other modifications (e.g. acetylation, phosphorylation and ubiquitination) in order to define a precise functional chromatin environment. In this review we focus on histone methylation and demethylation, as well as on the enzymes responsible for setting these marks. In particular we are describing novel concepts on the interdependence of histone modifications marks and discussing the molecular mechanisms governing this cross-talks.
126 citations
TL;DR: In this review, recent findings from UHTS are summarized and potential opportunities and challenges for broad adoption of these technologies in the plant science community are discussed.
Abstract: Ultra high-throughput sequencing (UHTS) technologies offer the potential to interrogate transcriptomes in detail that has traditionally been restricted to single gene surveys. For instance, it is now possible to globally define transcription start sites, polyadenylation signals, alternative splice sites and generate quantitative data on gene transcript accumulation in single tissues or cell types. These technologies are thus paving the way for whole genome transcriptomics and will undoubtedly lead to novel insights into plant development and biotic and abiotic stress responses. However, several challenges exist to making this technology broadly accessible to the plant research community. These include the current need for a computationally intensive analysis of data sets, a lack of standardized alignment and formatting procedures and a relatively small number of analytical software packages to interpret UHTS outputs. In this review we summarize recent findings from UHTS and discuss potential opportunities and challenges for broad adoption of these technologies in the plant science community.
122 citations
TL;DR: In the future, it is likely that the genomes of thousands of plants from mutagenised populations will be sequenced allowing for the identification of plants with mutations in specific genes to be done in silico.
Abstract: Genetic analysis represents a powerful tool that establishes a direct link between the biochemical function of a gene product and its role in vivo. Genome sequencing projects have identified large numbers of plant genes for which no role has yet been defined. To address this problem a number of techniques have been developed, over the last 15 years, to enable researchers to identify plants with mutations in genes of known sequence. These reverse genetic approaches include RNAi and related technologies and screening of populations mutagenised by insertion (PCR), deletion (PCR) and point mutation (TILLING), each with its own strengths and weaknesses. The development of next-generation sequencing techniques now allows such screening to be done by sequencing. In the future, it is likely that the genomes of thousands of plants from mutagenised populations will be sequenced allowing for the identification of plants with mutations in specific genes to be done in silico.
115 citations
TL;DR: Progress in the application of stable isotope dilution and stable isotopic metabolic labeling to metabolite identification and quantification are discussed and analytical limitations are discussed.
Abstract: Plant metabolomics has benefited from a rich array of pre-existing methodological approaches and bioanalytical knowledge for the characterization of the many chemically diverse classes of metabolites. While the field has pushed the implementation of unbiased and generally applicable strategies for metabolite extraction, fractionation and detection, significant challenges in fundamental activities such as compound identification and quantification still exist. This review provides an introduction to metabolomics terminology, methods and resources and discusses analytical limitations. Progress in the application of stable isotope dilution and stable isotopic metabolic labeling to metabolite identification and quantification are discussed. New strategies to address spatial distribution of metabolites via mass spectrometry-based imaging are also reviewed.
TL;DR: Some of the advantages and limitations of the ionomics approach as well as the important parameters to consider when designing ionomics experiments, and how to evaluate ionomics data are discussed.
Abstract: Ionomics is the study of elemental accumulation in living systems using high-throughput elemental profiling. This approach has been applied extensively in plants for forward and reverse genetics, screening diversity panels, and modeling of physiological states. In this review, I will discuss some of the advantages and limitations of the ionomics approach as well as the important parameters to consider when designing ionomics experiments, and how to evaluate ionomics data.
TL;DR: The results from multiple projects which attempted to exploit RNAi on a genome-wide scale suggest that there is a great deal of variation in the silencing efficacy between transgenic events, silencing targets and silencing-induced phenotype.
Abstract: RNAi refers to several different types of gene silencing mediated by small, dsRNA molecules. Over the course of 20 years, the scientific understanding of RNAi has developed from the initial observation of unexpected expression patterns to a sophisticated understanding of a multi-faceted, evolutionarily conserved network of mechanisms that regulate gene expression in many organisms. It has also been developed as a genetic tool that can be exploited in a wide range of species. Because transgene-induced RNAi has been effective at silencing one or more genes in a wide range of plants, this technology also bears potential as a powerful functional genomics tool across the plant kingdom. Transgene-induced RNAi has indeed been shown to be an effective mechanism for silencing many genes in many organisms, but the results from multiple projects which attempted to exploit RNAi on a genome-wide scale suggest that there is a great deal of variation in the silencing efficacy between transgenic events, silencing targets and silencing-induced phenotype. The results from these projects indicate several important variables that should be considered in experimental design prior to the initiation of functional genomics efforts based on RNAi silencing. In recent years, alternative strategies have been developed for targeted gene silencing, and a combination of approaches may also enhance the use of targeted gene silencing for functional genomics.
TL;DR: In this paper, the authors summarize the flexibility and performance of a selection of both types of experimental methods and argue that a serial combination of methods with different throughput and data type constitutes an optimal experimental strategy.
Abstract: Specific binding of transcription factors (TFs) determines in a large part the connectivity of gene regulatory networks as well as the quantitative level of gene expression. A multiplicity of both experimental and computational methods is currently used to discover and characterize the underlying TF-DNA interactions. Experimental methods can be further subdivided into in vitro- and in vivo-based approaches, each accenting different aspects of TF-binding events. In this review we summarize the flexibility and performance of a selection of both types of experimental methods. In conclusion, we argue that a serial combination of methods with different throughput and data type constitutes an optimal experimental strategy.
TL;DR: This review of methodologies that have been developed to profile the epigenome using next generation sequencing platforms will discuss these in terms of library preparation, sequence platforms and analysis techniques.
Abstract: Next generation sequencing has brought epigenomic studies to the forefront of current research. The power of massively parallel sequencing coupled to innovative molecular and computational techniques has allowed researchers to profile the epigenome at resolutions that were unimaginable only a few years ago. With early proof of concept studies published, the field is now moving into the next phase where the importance of method standardization and rigorous quality control are becoming paramount. In this review we will describe methodologies that have been developed to profile the epigenome using next generation sequencing platforms. We will discuss these in terms of library preparation, sequence platforms and analysis techniques.
TL;DR: This review highlights families of TFs that have expanded through gene duplication events to create species-unique repertoires in different evolutionary lineages, and discusses how the hierarchical structures of GRNs allow for flexible small to large-scale phenotypic changes.
Abstract: Nature is replete with examples of diverse cell types, tissues and body plans, forming very different creatures from genomes with similar gene complements. However, while the genes and the structures of proteins they encode can be highly conserved, the production of those proteins in specific cell types and at specific developmental time points might differ considerably between species. A full understanding of the factors that orchestrate gene expression will be essential to fully understand evolutionary variety. Transcription factor (TF) proteins, which form gene regulatory networks (GRNs) to act in cooperative or competitive partnerships to regulate gene expression, are key components of these unique regulatory programs. Although many TFs are conserved in structure and function, certain classes of TFs display extensive levels of species diversity. In this review, we highlight families of TFs that have expanded through gene duplication events to create species-unique repertoires in different evolutionary lineages. We discuss how the hierarchical structures of GRNs allow for flexible small to large-scale phenotypic changes. We survey evidence that explains how newly evolved TFs may be integrated into an existing GRN and how molecular changes in TFs might impact the GRNs. Finally, we review examples of traits that evolved due to lineage-specific TFs and species differences in GRNs.
TL;DR: In this review, some of the sequencing-based algorithms for detection of structural variations are described and the key issues in future development are discussed.
Abstract: Structural variations are widespread in the human genome and can serve as genetic markers in clinical and evolutionary studies. With the advances in the next-generation sequencing technology, recent methods allow for identification of structural variations with unprecedented resolution and accuracy. They also provide opportunities to discover variants that could not be detected on conventional microarray-based platforms, such as dosage-invariant chromosomal translocations and inversions. In this review, we will describe some of the sequencing-based algorithms for detection of structural variations and discuss the key issues in future development.
TL;DR: This review surveys recent epigenomic advances and their current and prospective application to the study of common diseases.
Abstract: The epigenome plays the pivotal role as interface between genome and environment. True genome-wide assessments of epigenetic marks, such as DNA methylation (methylomes) or chromatin modifications (chromatinomes), are now possible, either through high-throughput arrays or increasingly by second-generation DNA sequencing methods. The ability to collect these data at this level of resolution enables us to begin to be able to propose detailed questions, and interrogate this information, with regards to changes that occur due to development, lineage and tissue-specificity, and significantly those caused by environmental influence, such as ageing, stress, diet, hormones or toxins. Common complex traits are under variable levels of genetic influence and additionally epigenetic effect. The detection of pathological epigenetic alterations will reveal additional insights into their aetiology and how possible environmental modulation of this mechanism may occur. Due to the reversibility of these marks, the potential for sequence-specific targeted therapeutics exists. This review surveys recent epigenomic advances and their current and prospective application to the study of common diseases.
TL;DR: Significant advances in chromosome preparation, such as extended fiber-FISH, have greatly increased the axial resolution limits, while imaging and signal amplification technologies have improved the ability to detect small gene-sized probes.
Abstract: Plant cytogenetics has continued to flourish and make essential contributions to genomics projects by delineating marker order, defining contig gaps and revealing genome rearrangements. Here we review the field of plant cytogenetics from its conception through the eras of molecular biology and genomics. Significant advances in chromosome preparation, such as extended fiber-FISH, have greatly increased the axial resolution limits, while imaging and signal amplification technologies have improved our ability to detect small gene-sized probes. Combinations of traditional FISH technologies with chromatin immunocytochemistry serve to broaden the ability of plant cytogenetics to shed light on genome structure and organization. These advances are described, together with selected examples that illustrate the power of plant cytogenetics in guiding genome projects.
TL;DR: Re-sequencing of the gene and associated splice sites within the 105 624 bp genomic region of TRPM1 led to the discovery of 18 SNPs, which solidifies its functional role in both pigmentation and night vision.
Abstract: Leopard Complex spotting occurs in several breeds of horses and is caused by an incompletely dominant allele (LP). Homozygosity for LP is also associated with congenital stationary night blindness (CSNB) in Appaloosa horses. Previously, LP was mapped to a 6 cm region on ECA1 containing the candidate gene TRPM1 (Transient Receptor Potential Cation Channel, Subfamily M, Member 1) and decreased expression of this gene, measured by qRT-PCR, was identified as the likely cause of both spotting and ocular phenotypes. This study describes investigations for a mutation causing or associated with the Leopard Complex and CSNB phenotype in horses. Re-sequencing of the gene and associated splice sites within the 105 624 bp genomic region of TRPM1 led to the discovery of 18 SNPs. Most of the SNPs did not have a predictive value for the presence of LP. However, one SNP (ECA1:108,249,293 C>T) found within intron 11 had a strong (P < 0.0005), but not complete, association with LP and CSNB and thus is a good marker but unlikely to be causative. To further localize the association, 70 SNPs spanning over two Mb including the TRPM1 gene were genotyped in 192 horses from three different breeds segregating for LP. A single 173 kb haplotype associated with LP and CSNB (ECA1: 108,197,355- 108,370,150) was identified. Illumina sequencing of 300 kb surrounding this haplotype revealed 57 SNP variants. Based on their localization within expressed sequences or regions of high sequence conservation across mammals, six of these SNPs were considered to be the most likely candidate mutations. While the precise function of TRPM1 remains to be elucidated, this work solidifies its functional role in both pigmentation and night vision. Further, this work has identified several potential regulatory elements of the TRPM1 gene that should be investigated further in this and other species.
TL;DR: By integrating databases obtained from epigenome- and transcriptome-wide analyses, this work has the unique opportunity to identify all the imprinted genes in the human/mouse genomes.
Abstract: In the mid-1980s, elegant studies on mouse embryos revealed that both parental genomes are required for normal development leading to the discovery of genomic imprinting. Imprinting is a parent-of-origin-dependent epigenetic mechanism whereby a subset of autosomal genes is expressed from only one of the parental alleles. Imprinting control involves both DNA- and histone-methylation, which differentially mark the parental alleles. More than a hundred imprinted genes have been identified so far, many of which play important roles in the regulation of growth and development. Nonetheless, the full extent of imprinting and its biological functions remain underestimated. In this review, we describe recently developed strategies to identify novel imprinted genes and highlight the potential of combining several high throughput approaches. By integrating databases obtained from epigenome- and transcriptome-wide analyses, we now have the unique opportunity to identify all the imprinted genes in the human/mouse genomes.
TL;DR: Large groups of apoptosis genes, transcription factors and cytokines were found to be differentially expressed in infected monocyte-derived macrophages as well as several genes not previously linked to MAP-host interactions.
Abstract: Mycobacterium avium subspecies paratuberculosis (MAP) is a significant concern to the American and European dairy industries and possibly to human health. MAP possesses the rare ability to survive and replicate in infected macrophages, cells that are typically able to destroy pathogens. Little is known about what changes occur in MAP-infected macrophages that prevent phagosome maturation and lead to intracellular survival of the bacteria. In this study, a bovine immunologically specific cDNA microarray was used to study genes whose expression was altered in monocyte-derived macrophages (MDM) when these cells were infected with 10 different strains of MAP bacteria. Although we used MAP strains isolated from four different host species, cluster analysis of each strains influence in infected MDMs showed no species of origin specific MAP alterations in the host transcriptome. However, MAP strain K10 was observed as a clear outlier in the cluster analysis. Additionally, we observed two SuperShedder MAP strains clustering very closely together compared to the other strains in this study. Overall, microarray analysis yielded 78 annotated genes whose expression was altered by MAP infection, regardless of strain. Few of these genes have been previously studied in the context of Johne’s disease or other mycobacterium-caused diseases. Large groups of apoptosis genes, transcription factors and cytokines were found to be differentially expressed in infected monocyte-derived macrophages as well as several genes not previously linked to MAP-host interactions. Identifying novel host genes affected by MAP infection of macrophages may lead to a more complete picture of this complex host^ pathogen interaction.
TL;DR: This article focuses on three common sources of potential confounding effects: (i) random monoallelic expression in monoclonal cell populations, (ii) genetically determined monoalle Alic expression and (iii) contamination or infiltration of embryonic tissues with maternal material.
Abstract: Genomic imprinting refers to genes that are epigenetically programmed in the germline to express exclusively or preferentially one allele in a parent-of-origin manner. Expression-based genome-wide screening for the identification of imprinted genes has failed to uncover a significant number of new imprinted genes, probably because of the high tissue- and developmental-stage specificity of imprinted gene expression. A very large number of technical and biological artifacts can also lead to the erroneous evidence of imprinted gene expression. In this article, we focus on three common sources of potential confounding effects: (i) random monoallelic expression in monoclonal cell populations, (ii) genetically determined monoallelic expression and (iii) contamination or infiltration of embryonic tissues with maternal material. This last situation specifically applies to genes that occur as maternally expressed in the placenta. Beside the use of reciprocal crosses that are instrumental to confirm the parental specificity of expression, we provide additional methods for the detection and elimination of these situations that can be misinterpreted as cases of imprinted expression.
TL;DR: Gene-centered approaches that were employed to characterize GRNs are discussed and insights that were obtained into the global design principles of gene regulation in complex metazoan systems are described.
Abstract: Differential gene expression plays a critical role in the development and physiology of multicellular organisms. At a ‘systems level’ (e.g. at the level of a tissue, organ or whole organism), this process can be studied using gene regulatory network (GRN) models that capture physical and regulatory interactions between genes and their regulators. In the past years, significant progress has been made toward the mapping of GRNs using a variety of experimental and computational approaches. Here, we will discuss gene-centered approaches that we employed to characterize GRNs and describe insights that we have obtained into the global design principles of gene regulation in complex metazoan systems.
TL;DR: An overview of experimental and computational techniques for identifying and analyzing protein phosphorylation on a systems level is given.
Abstract: Protein kinase phosphorylation is central to the regulation and control of protein and cellular function. Over the past decade, the development of many high-throughput approaches has revolutionized the understanding of protein phosphorylation and allowed rapid and unbiased surveys of phosphoproteins and phosphorylation events. In addition to this technological advancement, there have also been computational improvements; recent studies on network models of protein phosphorylation have provided many insights into the cellular processes and pathways regulated by phosphorylation. This article gives an overview of experimental and computational techniques for identifying and analyzing protein phosphorylation on a systems level.
TL;DR: This review will discuss alterations in DNA methylation and histone modifications in cancer, with specific emphasis on imprinted loci.
Abstract: Genetic events alone cannot explain the entire process of carcinogenesis. It is estimated that there are more epigenetic alterations in cancer than DNA mutations, and disiphering driver and secondary events is essential to understand early processes of tumorigenesis. Epigenetic modifications control gene activity, governing whether a gene is transcribed or silent. In cancer, global patterns of two epigenetic marks, histone modifications and DNA methylation, are known to be extensively deregulated. Tumour cells are also characterized by loss-of-imprinting, a key epigenetic developmental mechanism. Genomic imprinting is the parent-of-origin, monoallelic expression of genes and is controlled by differentially DNA-methylated regions and allelic-histone modifications. With specific emphasis on imprinted loci this review will discuss alterations in DNA methylation and histone modifications in cancer. The recent advances in technology that might facilitate the identification and characterization of the epigenetic profiles of cancer will also be described.
TL;DR: The reduction of the multi-dimensional data sets of meat performance traits into lower dimensions of PC and the genetical genomics approach of eQTL analysis proved to be appropriate means to detect relevant biological pathways and to experimentally prioritize candidate genes.
Abstract: The benefit of functional genomics is to identify key pathways and functional networks of genes and candidate genes underlying the genetic control of phenotypes. Genetical genomics, i.e. the integration of genetic analysis and expression phenotypes, has the potential to uncover regulatory networks controlling the coordinated expression of genes and to map variation on the level of DNA affecting the mRNA expression. Here we illustrate our own attempts to apply functional genomics and genetical genomics approaches in order to identify functional networks of genes relevant to traits related to meat performance. Expression data of 74 M longissimus dorsi samples obtained using Affymetrix GeneChips were correlated with drip loss and principal components (PCs) with high loadings of meat quality traits. Functional annotation analyses revealed that differences in water holding capacity, early pH decline and ultimate pH were related to the ubiquitin-proteasome system, mitochondrial metabolic pathways and muscle structural aspects. In particular, 1279 genes were correlated with drip loss (P
TL;DR: It is plausible that differential penetrance and variation of age at diagnosis, which have been observed in patients with hereditary and non-hereditary retinoblastoma, respectively, are a consequence of imprinted expression of the RB1 gene.
Abstract: Recent data have revealed that the paradigmatic tumour suppressor gene RB1 on chromosome 13 is preferentially expressed from the maternal allele. Imprinted expression of RB1 is linked to a differentially methylated CpG island in intron 2 of this gene (CpG 85). On the paternal chromosome, CpG 85 is unmethylated and acts as a weak promoter of an alternative RB1 transcript. Paternal mRNA levels are probably reduced as the result of transcriptional interference of the regular promoter and the alternative promoter on this chromosome. CpG 85 is part of a truncated processed pseudogene (KIAA0649P) that integrated into the RB1 gene prior to the speciation of extant primates. It is plausible that differential penetrance and variation of age at diagnosis, which have been observed in patients with hereditary and non-hereditary retinoblastoma, respectively, are a consequence of imprinted expression of the RB1 gene. Interestingly, RB1 is imprinted in the same direction as CDKN1C, which operates upstream of RB1. The imprinting of two components of the same pathway indicates that there has been strong evolutionary selection for maternal inhibition of cell proliferation.
TL;DR: This review aspires to highlight the main features characterizing these kinds of executable models and what makes them uniquely qualified to reason about and analyze biological networks.
Abstract: As time goes by, it becomes more and more apparent that the puzzles of life involve more and more molecular pieces that fit together in increasingly complex ways. Genomics and Proteomics technologies nowadays, produce reliable and quantitative data that could potentially reveal all the molecular pieces of a particular puzzle. However, this is akin to the opening of Pandora’s box; and we are now facing the problem of integrating this vast amount of data with its incredible complexity into some coherent whole. With the aid of engineering methods designed to build and analyze computerized man-made systems, a new emerging field called ‘Executable Biology’ aims to create computer programmes that put together the pieces in ways that allows capturing their dynamicity and ultimately elucidating how molecular function generates cellular function. This review aspires to highlight the main features characterizing these kinds of executable models and what makes them uniquely qualified to reason about and analyze biological networks.
TL;DR: A distinct class of imprinted genes, which have arisen by retrotransposition, and which have the potential to be used as models for the dissection of the fundamental features and mechanisms required for imprinting are reviewed.
Abstract: Studies of large imprinted clusters, such as the Gnas locus, have revealed much about the significance of DNA methylation, transcription and other factors in the establishment and maintenance of imprinted gene expression. However, the complexity of such loci can make manipulating them and interpreting the results challenging. We review here a distinct class of imprinted genes, which have arisen by retrotransposition, and which have the potential to be used as models for the dissection of the fundamental features and mechanisms required for imprinting. They are also of interest in their own right, generating diversity in the transcriptome and providing raw material upon which selection can act.