Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2.

Abstract:

:Chronic neuropathic pain is affected by specifics of the precipitating neural pathology, psychosocial factors, and by genetic predisposition. Little is known about the identity of predisposing genes. Using an integrative approach, we discovered that CACNG2 significantly affects susceptibility to chronic pain following nerve injury. CACNG2 encodes for stargazin, a protein intimately involved in the trafficking of glutamatergic AMPA receptors. The protein might also be a Ca(2+) channel subunit. CACNG2 has previously been implicated in epilepsy. Initially, using two fine-mapping strategies in a mouse model (recombinant progeny testing [RPT] and recombinant inbred segregation test [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a 4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently, bioinformatics and whole-genome microarray expression analysis were used to narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided electrophysiological and behavioral evidence for the gene's functional role in pain processing. Finally, we showed that human CACNG2 polymorphisms are associated with chronic pain in a cohort of cancer patients who underwent breast surgery. Our findings provide novel information on the genetic basis of neuropathic pain and new insights into pain physiology that may ultimately enable better treatments.

journal_name

Genome Res

journal_title

Genome research

authors

Nissenbaum J,Devor M,Seltzer Z,Gebauer M,Michaelis M,Tal M,Dorfman R,Abitbul-Yarkoni M,Lu Y,Elahipanah T,delCanho S,Minert A,Fried K,Persson AK,Shpigler H,Shabo E,Yakir B,Pisanté A,Darvasi A

doi

10.1101/gr.104976.110

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

1180-90

issue

9

eissn

1088-9051

issn

1549-5469

pii

gr.104976.110

journal_volume

20

pub_type

杂志文章
  • High mutational rates of large-scale duplication and deletion in Daphnia pulex.

    abstract::Knowledge of the genome-wide rate and spectrum of mutations is necessary to understand the origin of disease and the genetic variation driving all evolutionary processes. Here, we provide a genome-wide analysis of the rate and spectrum of mutations obtained in two Daphnia pulex genotypes via separate mutation-accumula...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.191338.115

    authors: Keith N,Tucker AE,Jackson CE,Sung W,Lucas Lledó JI,Schrider DR,Schaack S,Dudycha JL,Ackerman M,Younge AJ,Shaw JR,Lynch M

    更新日期:2016-01-01 00:00:00

  • Impact of genomic structural variation in Drosophila melanogaster based on population-scale sequencing.

    abstract::Genomic structural variation (SV) is a major determinant for phenotypic variation. Although it has been extensively studied in humans, the nucleotide resolution structure of SVs within the widely used model organism Drosophila remains unknown. We report a highly accurate, densely validated map of unbalanced SVs compri...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.142646.112

    authors: Zichner T,Garfield DA,Rausch T,Stütz AM,Cannavó E,Braun M,Furlong EE,Korbel JO

    更新日期:2013-03-01 00:00:00

  • Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes.

    abstract::Mosaic mutations present in the germline have important implications for reproductive risk and disease transmission. We previously demonstrated a phenomenon occurring in the male germline, whereby specific mutations arising spontaneously in stem cells (spermatogonia) lead to clonal expansion, resulting in elevated mut...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.239186.118

    authors: Maher GJ,Ralph HK,Ding Z,Koelling N,Mlcochova H,Giannoulatou E,Dhami P,Paul DS,Stricker SH,Beck S,McVean G,Wilkie AOM,Goriely A

    更新日期:2018-12-01 00:00:00

  • Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk.

    abstract::Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here, we present sequential ChIP-bisulfite-sequencing (ChIP-BS-seq) as an approach to quantitatively assess DNA methylat...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.133728.111

    authors: Brinkman AB,Gu H,Bartels SJ,Zhang Y,Matarese F,Simmer F,Marks H,Bock C,Gnirke A,Meissner A,Stunnenberg HG

    更新日期:2012-06-01 00:00:00

  • Pattern of sequence variation across 213 environmental response genes.

    abstract::To promote the clinical and epidemiological studies that improve our understanding of human genetic susceptibility to environmental exposure, the Environmental Genome Project (EGP) has scanned 213 environmental response genes involved in DNA repair, cell cycle regulation, apoptosis, and metabolism for single nucleotid...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2730004

    authors: Livingston RJ,von Niederhausern A,Jegga AG,Crawford DC,Carlson CS,Rieder MJ,Gowrisankar S,Aronow BJ,Weiss RB,Nickerson DA

    更新日期:2004-10-01 00:00:00

  • Gene3D: structural assignment for whole genes and genomes using the CATH domain structure database.

    abstract::We present a novel web-based resource, Gene3D, of precalculated structural assignments to gene sequences and whole genomes. This resource assigns structural domains from the CATH database to whole genes and links these to their curated functional and structural annotations within the CATH domain structure database, th...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.213802

    authors: Buchan DW,Shepherd AJ,Lee D,Pearl FM,Rison SC,Thornton JM,Orengo CA

    更新日期:2002-03-01 00:00:00

  • A Plasmodium gene family encoding Maurer's cleft membrane proteins: structural properties and expression profiling.

    abstract::Upon invasion of the erythrocyte cell, the malaria parasite remodels its environment; in particular, it establishes a complex membrane network, which connects the parasitophorous vacuole to the host plasma membrane and is involved in protein transport and trafficking. We have identified a novel subtelomeric gene famil...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2126104

    authors: Sam-Yellowe TY,Florens L,Johnson JR,Wang T,Drazba JA,Le Roch KG,Zhou Y,Batalov S,Carucci DJ,Winzeler EA,Yates JR 3rd

    更新日期:2004-06-01 00:00:00

  • Computational identification of operons in microbial genomes.

    abstract::By applying graph representations to biochemical pathways, a new computational pipeline is proposed to find potential operons in microbial genomes. The algorithm relies on the fact that enzyme genes in operons tend to catalyze successive reactions in metabolic pathways. We applied this algorithm to 42 microbial genome...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.200602

    authors: Zheng Y,Szustakowski JD,Fortnow L,Roberts RJ,Kasif S

    更新日期:2002-08-01 00:00:00

  • Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.

    abstract::By analyzing 1,780,295 5'-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by m...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.4039406

    authors: Kimura K,Wakamatsu A,Suzuki Y,Ota T,Nishikawa T,Yamashita R,Yamamoto J,Sekine M,Tsuritani K,Wakaguri H,Ishii S,Sugiyama T,Saito K,Isono Y,Irie R,Kushida N,Yoneyama T,Otsuka R,Kanda K,Yokoi T,Kondo H,Wagatsuma M

    更新日期:2006-01-01 00:00:00

  • Probing genomic diversity and evolution of Escherichia coli O157 by single nucleotide polymorphisms.

    abstract::Infections by Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) are the predominant cause of bloody diarrhea and hemolytic uremic syndrome in the United States. In silico comparison of the two complete STEC O157 genomes (Sakai and EDL933) revealed a strikingly high level of sequence identity in orthologous pr...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.4759706

    authors: Zhang W,Qi W,Albert TJ,Motiwala AS,Alland D,Hyytia-Trees EK,Ribot EM,Fields PI,Whittam TS,Swaminathan B

    更新日期:2006-06-01 00:00:00

  • Computational and experimental identification of mirtrons in Drosophila melanogaster and Caenorhabditis elegans.

    abstract::Mirtrons are intronic hairpin substrates of the dicing machinery that generate functional microRNAs. In this study, we describe experimental assays that defined the essential requirements for entry of introns into the mirtron pathway. These data informed a bioinformatic screen that effectively identified functional mi...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.113050.110

    authors: Chung WJ,Agius P,Westholm JO,Chen M,Okamura K,Robine N,Leslie CS,Lai EC

    更新日期:2011-02-01 00:00:00

  • Genomic organization of the sex-determining and adjacent regions of the sex chromosomes of medaka.

    abstract::Sequencing of the human Y chromosome has uncovered the peculiarities of the genomic organization of a heterogametic sex chromosome of old evolutionary age, and has led to many insights into the evolutionary changes that occurred during its long history. We have studied the genomic organization of the medaka fish Y chr...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.5016106

    authors: Kondo M,Hornung U,Nanda I,Imai S,Sasaki T,Shimizu A,Asakawa S,Hori H,Schmid M,Shimizu N,Schartl M

    更新日期:2006-07-01 00:00:00

  • Ride the wavelet: A multiscale analysis of genomic contexts flanking small insertions and deletions.

    abstract::Recent studies have revealed that insertions and deletions (indels) are more different in their formation than previously assumed. What remains enigmatic is how the local DNA sequence context contributes to these differences. To investigate the relative impact of various molecular mechanisms to indel formation, we ana...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.088922.108

    authors: Kvikstad EM,Chiaromonte F,Makova KD

    更新日期:2009-07-01 00:00:00

  • Transcriptional enhancement by GATA1-occupied DNA segments is strongly associated with evolutionary constraint on the binding site motif.

    abstract::Tissue development and function are exquisitely dependent on proper regulation of gene expression, but it remains controversial whether the genomic signals controlling this process are subject to strong selective constraint. While some studies show that highly constrained noncoding regions act to enhance transcription...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.083089.108

    authors: Cheng Y,King DC,Dore LC,Zhang X,Zhou Y,Zhang Y,Dorman C,Abebe D,Kumar SA,Chiaromonte F,Miller W,Green RD,Weiss MJ,Hardison RC

    更新日期:2008-12-01 00:00:00

  • Gene expression profiling of single cells from archival tissue with laser-capture microdissection and Smart-3SEQ.

    abstract::RNA sequencing (RNA-seq) is a sensitive and accurate method for quantifying gene expression. Small samples or those whose RNA is degraded, such as formalin-fixed paraffin-embedded (FFPE) tissue, remain challenging to study with nonspecialized RNA-seq protocols. Here, we present a new method, Smart-3SEQ, that accuratel...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.234807.118

    authors: Foley JW,Zhu C,Jolivet P,Zhu SX,Lu P,Meaney MJ,West RB

    更新日期:2019-11-01 00:00:00

  • Natural genetic variation in yeast longevity.

    abstract::The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross be...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.136549.111

    authors: Stumpferl SW,Brand SE,Jiang JC,Korona B,Tiwari A,Dai J,Seo JG,Jazwinski SM

    更新日期:2012-10-01 00:00:00

  • Inference of population genetic parameters in metagenomics: a clean look at messy data.

    abstract::Metagenomic projects generate short, overlapping fragments of DNA sequence, each deriving from a different individual. We report a new method for inferring the scaled mutation rate, theta = 2Neu, and the scaled exponential growth rate, R = Ner, from the site-frequency spectrum of these data while accounting for sequen...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.5431206

    authors: Johnson PL,Slatkin M

    更新日期:2006-10-01 00:00:00

  • Multiparameter functional diversity of human C2H2 zinc finger proteins.

    abstract::C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.209643.116

    authors: Schmitges FW,Radovani E,Najafabadi HS,Barazandeh M,Campitelli LF,Yin Y,Jolma A,Zhong G,Guo H,Kanagalingam T,Dai WF,Taipale J,Emili A,Greenblatt JF,Hughes TR

    更新日期:2016-12-01 00:00:00

  • Comparative analysis of mammalian Y chromosomes illuminates ancestral structure and lineage-specific evolution.

    abstract::Although more than thirty mammalian genomes have been sequenced to draft quality, very few of these include the Y chromosome. This has limited our understanding of the evolutionary dynamics of gene persistence and loss, our ability to identify conserved regulatory elements, as well our knowledge of the extent to which...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.154286.112

    authors: Li G,Davis BW,Raudsepp T,Pearks Wilkerson AJ,Mason VC,Ferguson-Smith M,O'Brien PC,Waters PD,Murphy WJ

    更新日期:2013-09-01 00:00:00

  • Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay.

    abstract::Large-scale genetic studies are highly dependent on efficient and scalable multiplex SNP assays. In this study, we report the development of Molecular Inversion Probe technology with four-color, single array detection, applied to large-scale genotyping of up to 12,000 SNPs per reaction. While generating 38,429 SNP ass...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.3185605

    authors: Hardenbol P,Yu F,Belmont J,Mackenzie J,Bruckner C,Brundage T,Boudreau A,Chow S,Eberle J,Erbilgin A,Falkowski M,Fitzgerald R,Ghose S,Iartchouk O,Jain M,Karlin-Neumann G,Lu X,Miao X,Moore B,Moorhead M,Namsaraev E,

    更新日期:2005-02-01 00:00:00

  • Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs.

    abstract::Fetal liver intriguingly consists of hepatic parenchymal cells and hematopoietic stem/progenitor cells. Human fetal liver aged 22 wk of gestation (HFL22w) corresponds to the turning point between immigration and emigration of the hematopoietic system. To gain further molecular insight into its developmental and functi...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.175501

    authors: Yu Y,Zhang C,Zhou G,Wu S,Qu X,Wei H,Xing G,Dong C,Zhai Y,Wan J,Ouyang S,Li L,Zhang S,Zhou K,Zhang Y,Wu C,He F

    更新日期:2001-08-01 00:00:00

  • Thermophilic bacteria strictly obey Szybalski's transcription direction rule and politely purine-load RNAs with both adenine and guanine.

    abstract::When transcription is to the right of the promoter, the "top," mRNA-synonymous strand of DNA tends to be purine-rich. When transcription is to the left of the promoter, the top, mRNA-template strand tends to be pyrimidine-rich. This transcription-direction rule suggests that there has been an evolutionary selection pr...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.10.2.228

    authors: Lao PJ,Forsdyke DR

    更新日期:2000-02-01 00:00:00

  • Alternative approach to a heavy weight problem.

    abstract::Obesity is reaching epidemic proportions in developed countries and represents a significant risk factor for hypertension, heart disease, diabetes, and dyslipidemia. Splicing mutations constitute at least 14% of disease-causing mutations, thus implicating polymorphisms that affect splicing as likely candidates for dis...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.6661308

    authors: Goren A,Kim E,Amit M,Bochner R,Lev-Maor G,Ahituv N,Ast G

    更新日期:2008-02-01 00:00:00

  • A platform for curated products from novel open reading frames prompts reinterpretation of disease variants.

    abstract::Recent evidence from proteomics and deep massively parallel sequencing studies have revealed that eukaryotic genomes contain substantial numbers of as-yet-uncharacterized open reading frames (ORFs). We define these uncharacterized ORFs as novel ORFs (nORFs). nORFs in humans are mostly under 100 codons and are found in...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.263202.120

    authors: Neville MDC,Kohze R,Erady C,Meena N,Hayden M,Cooper DN,Mort M,Prabakaran S

    更新日期:2021-01-19 00:00:00

  • Methylation analysis of a marsupial X-linked CpG island by bisulfite genomic sequencing.

    abstract::Paternal X chromosome inactivation occurs in rodent extraembryonic membranes and in all tissues of marsupials. Methylation of CpG islands occurs on the inactive X in eutherians and is considered to be a stabilizing mechanism. The only previous study of a marsupial X-linked CpG island was of the G6PD gene of the Virgin...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.6.2.114

    authors: Loebel DA,Johnston PG

    更新日期:1996-02-01 00:00:00

  • New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling.

    abstract::We have identified three new families of insulin homologs in Caenorhabditis elegans. In two of these families, concerted mutations suggest that an additional disulfide bond links B and A domains, and that the A-domain internal disulfide bond is substituted by a hydrophobic interaction. Homology modeling remarkably con...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.8.4.348

    authors: Duret L,Guex N,Peitsch MC,Bairoch A

    更新日期:1998-04-01 00:00:00

  • An extraordinary retrotransposon family encoding dual endonucleases.

    abstract::Retrotransposons commonly encode a reverse transcriptase (RT), but other functional domains are variable. The acquisition of new domains is the dominant evolutionary force that brings structural variety to retrotransposons. Non-long-terminal-repeat (non-LTR) retrotransposons are classified into two groups by their str...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.3271405

    authors: Kojima KK,Fujiwara H

    更新日期:2005-08-01 00:00:00

  • Background-suppressed live visualization of genomic loci with an improved CRISPR system based on a split fluorophore.

    abstract::The higher-order structural organization and dynamics of the chromosomes play a central role in gene regulation. To explore this structure-function relationship, it is necessary to directly visualize genomic elements in living cells. Genome imaging based on the CRISPR system is a powerful approach but has limited appl...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.260018.119

    authors: Chaudhary N,Nho SH,Cho H,Gantumur N,Ra JS,Myung K,Kim H

    更新日期:2020-09-01 00:00:00

  • A human cDNA expression library in yeast enriched for open reading frames.

    abstract::We developed a high-throughput technique for the generation of cDNA libraries in the yeast Saccharomyces cerevisiae which enables the selection of cloned cDNA inserts containing open reading frames (ORFs). For direct screening of random-primed cDNA libraries, we have constructed a yeast shuttle/expression vector, the ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.181501

    authors: Holz C,Lueking A,Bovekamp L,Gutjahr C,Bolotina N,Lehrach H,Cahill DJ

    更新日期:2001-10-01 00:00:00

  • Evolution of a genomic regulatory domain: the role of gene co-option and gene duplication in the Enhancer of split complex.

    abstract::The Drosophila Enhancer of split complex [E(spl)-C] is a remarkable complex of genes many of which are effectors or modulators of Notch signaling. The complex contains different classes of genes including four bearded genes and seven basic helix-loop-helix (bHLH) genes. We examined the evolution of this unusual comple...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.104794.109

    authors: Duncan EJ,Dearden PK

    更新日期:2010-07-01 00:00:00