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Author

Rui Chen

Bio: Rui Chen is an academic researcher from Human Genome Sequencing Center. The author has contributed to research in topics: Medicine & Biology. The author has an hindex of 2, co-authored 2 publications receiving 508 citations.
Topics: Medicine, Biology, Genetics, Gene, Exome

Papers
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Journal ArticleDOI
26 Aug 2011-Science
TL;DR: The results show that the cis-regulatory evolution of a single transcription factor can repeatedly drive the convergent evolution of complex color patterns in distantly related species, thus blurring the distinction between convergence and homology.
Abstract: Mimicry—whereby warning signals in different species evolve to look similar—has long served as a paradigm of convergent evolution. Little is known, however, about the genes that underlie the evolution of mimetic phenotypes or to what extent the same or different genes drive such convergence. Here, we characterize one of the major genes responsible for mimetic wing pattern evolution in Heliconius butterflies. Mapping, gene expression, and population genetic work all identify a single gene, optix, that controls extreme red wing pattern variation across multiple species of Heliconius. Our results show that the cis-regulatory evolution of a single transcription factor can repeatedly drive the convergent evolution of complex color patterns in distantly related species, thus blurring the distinction between convergence and homology.

429 citations

Journal ArticleDOI
TL;DR: Detailed characterize nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium (LD), and candidate gene expression patterns across two unlinked genomic intervals that control yellow and red wing pattern variation among mimetic forms of Heliconius erato and provides convincing evidence for parallel changes in gene regulation across co-mimetic lineages.
Abstract: Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection. The genes controlling pattern variation are classic examples of Mendelian loci of large effect, where allelic variation causes large and discrete phenotypic changes and is responsible for both convergent and highly divergent wing pattern evolution across the genus. We characterize nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium (LD), and candidate gene expression patterns across two unlinked genomic intervals that control yellow and red wing pattern variation among mimetic forms of Heliconius erato. Despite very strong natural selection on color pattern, we see neither a strong reduction in genetic diversity nor evidence for extended LD across either patterning interval. This observation highlights the extent that recombination can erase the signature of selection in natural populations and is consistent with the hypothesis that either the adaptive radiation or the alleles controlling it are quite old. However, across both patterning intervals we identified SNPs clustered in several coding regions that were strongly associated with color pattern phenotype. Interestingly, coding regions with associated SNPs were widely separated, suggesting that color pattern alleles may be composed of multiple functional sites, conforming to previous descriptions of these loci as "supergenes." Examination of gene expression levels of genes flanking these regions in both H. erato and its co-mimic, H. melpomene, implicate a gene with high sequence similarity to a kinesin as playing a key role in modulating pattern and provides convincing evidence for parallel changes in gene regulation across co-mimetic lineages. The complex genetic architecture at these color pattern loci stands in marked contrast to the single casual mutations often identified in genetic studies of adaptation, but may be more indicative of the type of genetic changes responsible for much of the adaptive variation found in natural populations.

120 citations

Journal ArticleDOI
TL;DR: It is found that postnatal epigenetic maturation is markedly cell type and sex specific and occurs in genomic regions enriched for heritability of body mass index in humans, providing a rich resource for epigenetic analyses of developmental programming of energy balance.
Abstract: Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain’s energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and occurs in genomic regions enriched for heritability of body mass index in humans. Our results offer a potential explanation for both the limited ontogenic windows for and sex differences in sensitivity to developmental programming of obesity and provide a rich resource for epigenetic analyses of developmental programming of energy balance.

3 citations

Journal ArticleDOI
TL;DR: The findings demonstrated the therapeutic efficacy of gene therapy in treating Tlcd3b mutant retina, laying the foundation for developing future therapy for TLCD3B retinopathy.
Abstract: Purpose The purpose of this study was to assess the therapeutic efficacy of rAAV8-hGRK1-Tlcd3b in a Tlcd3b−/− mouse model of retinal generation and validate TLCD3B's role as a ceramide synthase in vivo. Methods Using Tlcd3b−/− mice as an inherited retinal disease animal model, we performed subretinal injection of rAAV8-hGRK1-Tlcd3b and evaluated the efficacy of gene replacement therapy. Tlcd3b−/− mice were treated at two time points: postnatal day 21 (P21) and postnatal day 120 (P120) with various dosages. Results Tlcd3b overexpression rescued retinal degeneration in the mutant mice, as indicated by significantly improved photoreceptor function and preservation of photoreceptor cells over the course of 1 year. Although Tlcd3b is expressed in all cell types in the retina, photoreceptor cell-specific expression of Tlcd3b is sufficient to rescue the phenotype, indicating the primary function of TLCD3B is in photoreceptors. Consistent with the idea that TLCD3B is a ceramide synthase, mass spectrometry analyses of the mutant retina indicate the reduction of C16-, C18-, and C20-ceramides in the retina, which are restored with Tlcd3b overexpression. Conclusions Our findings demonstrated the therapeutic efficacy of gene therapy in treating Tlcd3b mutant retina, laying the foundation for developing future therapy for TLCD3B retinopathy.

2 citations

Journal ArticleDOI
TL;DR: It is shown that BCL6 co-repressor (BCOR), a Polycomb repressive complex 1 factor mutated in various cancers, is involved in photoreceptor degenerative diseases and that the human BCOR mutants cause degeneration when expressed in the mouse retina and have enhanced repressive activity on OTX2.
Abstract: Many transcription factors regulating the production, survival, and function of photoreceptor cells have been identified, but little is known about transcriptional co-regulators in retinal health and disease. Here, we show that BCL6 co-repressor (BCOR), a Polycomb repressive complex 1 factor mutated in various cancers, is involved in photoreceptor degenerative diseases. Using proteomics and transcription assays, we report that BCOR interacts with the transcription factors CRX and OTX2 and reduces their ability to activate the promoters of photoreceptor-specific genes. CUT&RUN sequencing further shows that BCOR shares genome-wide binding profiles with CRX/OTX2, consistent with a general co-repression activity. We also identify missense mutations in human BCOR in five families that have no evidence of cancer but present severe early-onset X-linked retinal degeneration. Last, we show that the human BCOR mutants cause degeneration when expressed in the mouse retina and have enhanced repressive activity on OTX2. These results uncover a role for BCOR in photoreceptors in both health and disease.

1 citations


Cited by
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Journal Article
Fumio Tajima1
30 Oct 1989-Genomics
TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.

11,521 citations

Journal ArticleDOI
Kanchon K. Dasmahapatra1, James R. Walters2, Adriana D. Briscoe3, John W. Davey, Annabel Whibley, Nicola J. Nadeau2, Aleksey V. Zimin4, Daniel S.T. Hughes5, Laura Ferguson5, Simon H. Martin2, Camilo Salazar6, Camilo Salazar2, James J. Lewis3, Sebastian Adler7, Seung-Joon Ahn8, Dean A. Baker9, Simon W. Baxter2, Nicola Chamberlain10, Ritika Chauhan11, Brian A. Counterman12, Tamas Dalmay11, Lawrence E. Gilbert13, Karl H.J. Gordon14, David G. Heckel8, Heather M. Hines5, Katharina J. Hoff7, Peter W. H. Holland5, Emmanuelle Jacquin-Joly15, Francis M. Jiggins, Robert T. Jones, Durrell D. Kapan16, Durrell D. Kapan17, Paul J. Kersey, Gerardo Lamas, Daniel Lawson, Daniel Mapleson11, Luana S. Maroja18, Arnaud Martin3, Simon Moxon19, William J. Palmer2, Riccardo Papa20, Alexie Papanicolaou14, Yannick Pauchet8, David A. Ray12, Neil Rosser1, Steven L. Salzberg21, Megan A. Supple22, Alison K. Surridge2, Ayşe Tenger-Trolander10, Heiko Vogel8, Paul A. Wilkinson23, Derek Wilson, James A. Yorke4, Furong Yuan3, Alexi Balmuth24, Cathlene Eland, Karim Gharbi, Marian Thomson, Richard A. Gibbs25, Yi Han25, Joy Jayaseelan25, Christie Kovar25, Tittu Mathew25, Donna M. Muzny25, Fiona Ongeri25, Ling-Ling Pu25, Jiaxin Qu25, Rebecca Thornton25, Kim C. Worley25, Yuanqing Wu25, Mauricio Linares26, Mark Blaxter, Richard H. ffrench-Constant27, Mathieu Joron, Marcus R. Kronforst10, Sean P. Mullen28, Robert D. Reed3, Steven E. Scherer25, Stephen Richards25, James Mallet10, James Mallet1, W. Owen McMillan, Chris D. Jiggins6, Chris D. Jiggins2 
05 Jul 2012-Nature
TL;DR: It is inferred that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation.
Abstract: Sequencing of the genome of the butterfly Heliconius melpomene shows that closely related Heliconius species exchange protective colour-pattern genes promiscuously.

1,103 citations

Journal ArticleDOI
TL;DR: This work shows how cis-regulatory activity can diverge and how studies of cis-Regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.
Abstract: Cis-regulatory sequences, such as enhancers and promoters, control development and physiology by regulating gene expression. Mutations that affect the function of these sequences contribute to phenotypic diversity within and between species. With many case studies implicating divergent cis-regulatory activity in phenotypic evolution, researchers have recently begun to elucidate the genetic and molecular mechanisms that are responsible for cis-regulatory divergence. Approaches include detailed functional analysis of individual cis-regulatory elements and comparing mechanisms of gene regulation among species using the latest genomic tools. Despite the limited number of mechanistic studies published to date, this work shows how cis-regulatory activity can diverge and how studies of cis-regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.

919 citations

Journal ArticleDOI
TL;DR: Emergent trends and gaps in understanding are identified, new approaches to more fully integrate genomics into speciation research are proposed, and an integrative definition of the field of speciation genomics is provided.
Abstract: Speciation is a fundamental evolutionary process, the knowledge of which is crucial for understanding the origins of biodiversity. Genomic approaches are an increasingly important aspect of this research field. We review current understanding of genome-wide effects of accumulating reproductive isolation and of genomic properties that influence the process of speciation. Building on this work, we identify emergent trends and gaps in our understanding, propose new approaches to more fully integrate genomics into speciation research, translate speciation theory into hypotheses that are testable using genomic tools and provide an integrative definition of the field of speciation genomics.

875 citations

Journal ArticleDOI
TL;DR: Mistletoe lacks an author’s index, limiting the value of the book for anyone looking for specific papers, and will be of value to ethnobotanists, anyone interested in alternative medicines, and students of mistletoes and parasitic plants.
Abstract: ‘‘Gentlemen don’t need mistletoe’’ said the Christmas whiskey billboard I saw recently in Florida, a garish reminder of how much mistletoe lore is embedded in western society. Mistletoe The Genus Viscum, one in the series of medicinal and aromatic plants for industry and academic researchers, centers on the mistletoe in this advertisement, the common European mistletoe,Viscum album. There are helpful discussions on African, Asian, and Argentine mistletoes and their uses but the corpus of the book deals with V. album. Viscum album, considered sacred by the Druids, is no doubt the most widely used parasitic angiosperm for various health concoctions. As a result, much has been learned about its biochemistry and pharmaceutical potential. A great deal of the work on the culture and utilization ofV. album has been done by investigators at Institute Hiscia Center for Cancer Research in Switzerland where votaries of Rudolf Steiner’s distinct form of homeopathy have used mistletoe extracts (‘‘Iscador’’) for many years in cancer treatment. Mistletoe collected from less common hosts are considered to have greater efficacy in preparation of Iscador. As a result, there is a helpful chapter on culturing V. album which is not as difficult as might be imagined for an obligate parasite. Most of the chapters deal with the medicinal aspects of mistletoe including toxicology, clinical aspects, chemistry, and biochemistry emphasizing the lectins which are one of the more desirable compounds produced by the parasite. I found the treatment by Bu ̈ssing (Biological and pharmacological properties of Viscum album L.) helpful because it reviews the link between folk and modern medicine. However, several relevant papers were omitted which are included in a recent excellent review of mistletoes (Watson 2001). Like many books with a diversity of authors, the quality of chapters varies. Obviously produced as a reference volume, Mistletoe lacks an extensive index. Especially aggravating is the lack of an author’s index, limiting the value of the book for anyone looking for specific papers. These days, $70 for a hardbound monograph is reasonable. Color images are well-produced but some of the black and white figures are blurry in my copy. This volume will be of value to ethnobotanists, anyone interested in alternative medicines, and students of mistletoes and parasitic plants. LITERATURE CITED

752 citations