Abstract：
:Both complex disorders and monogenetic diseases are often modulated in their phenotype by further genetic, epigenetic or extrinsic factors. This gives rise to extensive phenotypic variability and potentially protection from disease manifestations, known as incomplete penetrance. Approaches including whole transcriptome, exome, genome, methylome or proteome analyses of highly discordant phenotypes in a few individuals harboring mutations at the same locus can help to identify these modifiers. This review describes the complexity of modifying factors of one of the most frequent autosomal recessively inherited disorders in humans, spinal muscular atrophy (SMA). We will outline how this knowledge contributes to understanding of the regulatory networks and molecular pathology of SMA and how this knowledge will influence future approaches to therapies.
journal_name
Curr Opin Genet Devjournal_title
Current opinion in genetics & developmentauthors
Wirth B,Garbes L,Riessland Mdoi
10.1016/j.gde.2013.03.003subject
Has Abstractpub_date
2013-06-01 00:00:00pages
330-8issue
3eissn
0959-437Xissn
1879-0380pii
S0959-437X(13)00046-4journal_volume
23pub_type
杂志文章,评审abstract：:The advent of gene targeting in the mouse has led to rapid advances in the identification of factors controlling gene expression that are essential for normal hematopoietic development. Recent work has also uncovered roles for some of these factors in leukemogenesis and in the global regulation of chromatin structure....
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(99)00008-8
更新日期：1999-10-01 00:00:00
abstract：:Models in developmental biology continue to yield valuable insights, yet do not play a strong role as guides to experiment. This may be because of the largely unexplored complexity of most developing organisms, and the fact that the most powerful models work at a very abstract level. In Dictyostelium discoideum, howev...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(05)80186-8
更新日期：1992-08-01 00:00:00
abstract：:Allele-specific gene expression can influence disease traits. Non-coding germline genetic variants that alter regulatory elements can cause allele-specific gene expression and contribute to cancer susceptibility. In tumors, both somatic copy number alterations and somatic single nucleotide variants have been shown to ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2020.10.007
更新日期：2020-12-28 00:00:00
abstract：:In recent years, studies of cis-regulatory mechanisms have evolved from a predominant focus on promoter regions to the realization that spatial and temporal gene regulation is frequently driven by long-range enhancer clusters that operate within chromosomal compartments. This increased understanding of genome function...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2015.08.009
更新日期：2015-08-01 00:00:00
abstract：:Natural selection drives evolving populations up the fitness landscape, the projection from nucleotide sequence space to organismal reproductive success. While it has long been appreciated that topographic complexities on fitness landscapes can arise only as a consequence of epistatic interactions between mutations, e...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2013.10.007
更新日期：2013-12-01 00:00:00
abstract：:TGFβ acts as a potent tumor suppressor and tumor promoter in a context dependent manner. Tumor suppressive functions include inhibition of cell proliferation, induction of apoptosis and regulation of autophagy. As tumors develop they switch their response to TGFβ and utilise this factor as a potent promoter of cell mo...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2010.12.004
更新日期：2011-02-01 00:00:00
abstract：:Chromatin-based epigenetic inheritance cooperates with cis-acting DNA sequence information to propagate gene expression states and chromosome architecture across cell division cycles. Histone proteins and their modifications are central components of epigenetic systems but how, and to what extent, they are propagated ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2012.11.002
更新日期：2013-04-01 00:00:00
abstract：:Differential gene expression gives rise to the many cell types of complex organisms. Enhancers regulate transcription by binding transcription factors (TFs), which in turn recruit cofactors to activate RNA Polymerase II at core promoters. Transcriptional regulation is typically mediated by distinct combinations of TFs...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2016.12.007
更新日期：2017-04-01 00:00:00
abstract：:Population data suggest that many parasitic protozoa (e.g. Trypanosoma, Leishmania, Entamoeba and Giardia) reproduce clonally, but this hypothesis has been highly controversial for Plasmodium falciparum. Although reproduction is predominantly clonal in the enteric bacteria Escherichia coli and Salmonella, the level of...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(05)80119-4
更新日期：1992-12-01 00:00:00
abstract：:Cellular fate reprogramming holds great promise to generate functional cell types for replenishing new cells and restoring functional loss. Inspired by transcription factor-induced reprogramming, the field of cellular reprogramming has greatly advanced and developed into divergent streams of reprogramming approaches. ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2018.05.004
更新日期：2018-10-01 00:00:00
abstract：:Cohesin defines the topology of chromosomes in mitosis and meiosis by holding sister chromatids together; more recently a role for cohesin in chromatin organisation and gene expression in interphase has emerged. ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2011.11.003
更新日期：2012-04-01 00:00:00
abstract：:The definitive endoderm (DE) was first defined as the innermost germ layer found in all metazoan embryos. During development, it gives rise to a vast array of specialized epithelial cell types lining the respiratory and digestive systems, and contributes to associated organs such as thyroid, thymus, lungs, liver, and ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2012.05.002
更新日期：2012-08-01 00:00:00
abstract：:Recent studies of beta-globin gene expression have concentrated on the analysis of factor binding and chromatin structure within the endogenous locus. These studies have more precisely defined the extent and nature of the active chromosomal domain and the elements that organize it. Surprisingly, the beta-globin locus ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(02)00283-6
更新日期：2002-04-01 00:00:00
abstract：:Recent developments in technology have made it possible to create high resolution genome-wide maps of histone marks, DNA binding proteins and physical interactions along genomic regions. Chromatin features are found together in different combinations, dividing the genome up into domains with distinct functional proper...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2012.11.011
更新日期：2013-04-01 00:00:00
abstract：:Multiple histone-modifying enzymes have been identified in the past several years. Much has been learned regarding the biochemistry of these enzymes and their effects on gene expression in cultured cells. However, the functions of these factors during development are still largely unknown. Recent genetic studies indic...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2006.02.002
更新日期：2006-04-01 00:00:00
abstract：:The evolutionary process of divergence, which ultimately leads to the generation of new species, is thought to occur usually without any gene exchange between the diverging populations. However, until the recent growth of multi-locus datasets, and the development of new population genetic methods, it has been very dif...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2006.10.005
更新日期：2006-12-01 00:00:00
abstract：:Recent studies on transposable elements (TEs) have shed light on the mechanisms that have shaped their evolution. In addition to accumulating nucleotide substitutions over evolutionary time, TEs appear to be especially prone to genetic rearrangements and vertical transmissions across even distantly related species. As...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/0959-437x(93)90005-a
更新日期：1993-12-01 00:00:00
abstract：:To understand organ morphogenetic mechanisms, it is essential to clarify how spatiotemporally-regulated molecular/cellular dynamics causes physical tissue deformation. In the case of vertebrate limb development, while some of the genes and oriented cell behaviors underlying morphogenesis have been revealed, tissue def...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2017.04.005
更新日期：2017-08-01 00:00:00
abstract：:Telomerase regulation and telomere shortening act as a strong tumor suppressor mechanism in human somatic cells. Point mutations in the promoter of telomerase reverse transcriptase (TERT) are the most frequent non-coding mutation in cancer. These TERT promoter mutations (TPMs) create de novo ETS factor binding sites u...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2020.02.001
更新日期：2020-02-01 00:00:00
abstract：:Gibberellins (GAs) affect several growth and developmental responses during the plant life cycle. Components essential for GA perception and GA signaling have been identified in rice and Arabidopsis and are conserved among vascular plants but not in Physcomitrella patens. The recent observation that DELLAs bind in nuc...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2008.05.004
更新日期：2008-08-01 00:00:00
abstract：:All the aspects of transcription are controlled by complexes that modify or remodel chromatin at the level of individual genes, gene clusters, or whole chromosomes. The MSL complex that is responsible for dosage compensation in Drosophila is an example of complexes that operate at the whole-chromosome level on the tra...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2009.10.004
更新日期：2009-12-01 00:00:00
abstract：:The largest subunit of eukaryotic RNA polymerase II has an unusual tandemly repeated heptapeptide sequence at its carboxyl terminus. The function of this evolutionarily conserved carboxy-terminal domain is unknown; however, new evidence links it to the formation of a large multi-component RNA polymerase II complex pos...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/0959-437x(95)80009-3
更新日期：1995-04-01 00:00:00
abstract：:Recent advances in cell reprogramming via employing different sets of factors, which allows generation of various cell types that are beyond the downstream developmental lineages from the starting cell type, provide significant opportunities to study fundamental biology and hold enormous promise in regenerative medici...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2014.09.006
更新日期：2014-10-01 00:00:00
abstract：:Transcription is the first step in gene expression, and its regulation underlies multicellular development and the response to environmental changes. Most studies of transcriptional regulation have focused on the recruitment of RNA polymerase to promoters. However, recent work has shown that, for many promoters, post-...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2007.12.008
更新日期：2008-04-01 00:00:00
abstract：:Morphogen gradients regulate the patterning and growth of many tissues, hence a key question is how they are established and maintained during development. Theoretical descriptions have helped to explain how gradient shape is controlled by the rates of morphogen production, spreading and degradation. These effective r...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2012.08.004
更新日期：2012-12-01 00:00:00
abstract：:The recent discovery of self-splicing introns in cyanobacteria has given renewed interest to the question of whether introns may have been present in the ancestor of all living things. The properties of introns in genes of bacteria and bacteriophages are discussed in the context of their possible origin and biological...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(05)80195-9
更新日期：1991-12-01 00:00:00
abstract：:Understanding the past is to understand the present. Mammalian life, with all its complexity comes from a humble beginning of a single fertilized egg cell. Achieving this requires an enormous diversification of cellular function, the majority of which is generated through a series of cellular decisions during embryoge...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2015.08.002
更新日期：2015-10-01 00:00:00
abstract：:The conserved homeobox (Hox) gene cluster is neither conserved nor clustered in the nematode Caenorhabditis elegans. Instead, C. elegans has a reduced and dispersed gene complement that is the result the loss of Hox genes in stages throughout its evolutionary history. The roles of Hox genes in patterning the nematode ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2003.10.009
更新日期：2003-12-01 00:00:00
abstract：:Expansions of microsatellite DNA repeats contribute to the inheritance of nearly 30 developmental and neurological disorders. Significant progress has been made in elucidating the molecular mechanisms of repeat expansions using various model organisms and mammalian cell culture, and models implicating nearly all DNA t...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2013.04.009
更新日期：2013-06-01 00:00:00
abstract：:Eukaryotic organisms have the remarkable ability to inherit states of gene activity without altering the underlying DNA sequence. This epigenetic inheritance can persist over thousands of years, providing an alternative to genetic mutations as a substrate for natural selection. Epigenetic inheritance might be propagat...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2005.07.002
更新日期：2005-10-01 00:00:00
