Intergenomic consensus in multifactorial inheritance loci: the case of multiple sclerosis

Serrano-Fernández, Pablo; Ibrahim, Saleh M.; Uk, Zettl; Thiesen, Hans‐Juergen; Gödde, René; Epplen, Jörg T.; Möller, Steffen

doi:10.1038/sj.gene.6364134

Cited by 18 publications

(11 citation statements)

References 48 publications

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“…These factors are known to influence the incidence, severity, and course of the disease, as well as the histopathological features of EAE (Lorentzen et al 1995;Storch et al 1998). Nevertheless, a number of consensus regions have been identified to date, indicating that pathological mechanisms are shared between the most commonly used EAE models (Serrano-Fernández et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, every consensus region remains hypothetical unless confirmed by other methods as addressed in this work. Eae3, a previously described QTL for myelin-induced EAE residing on rat chromosome 10 (Roth et al 1999) that comprises Eae18a, harbors several narrow intergenomic consensus regions (Serrano-Fernández et al 2004). This article describes a fine mapping of Eae18a by independent in silico mapping and by linkage analysis using the 10th generation of a rat advanced intercross line (AIL) (Darvasi and Soller 1995).…”

Section: Ultiple Sclerosis (Ms) Is a Chronic Inflammatorymentioning

confidence: 99%

“…Both methodology and references for the human, mouse, and rat disease-associated regions have been previously reported (Serrano-Fernández et al 2004.…”

Section: Ailmentioning

confidence: 99%

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Definition of a 1.06-Mb Region Linked to Neuroinflammation in Humans, Rats and Mice

et al. 2006

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Unbiased identification of susceptibility genes might provide new insights into pathogenic mechanisms that govern complex inflammatory diseases such as multiple sclerosis. In this study we fine mapped Eae18a, a region on rat chromosome 10 that regulates experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. We utilized two independent approaches: (1) in silico mapping based on sequence similarity between human multiple sclerosis susceptibility regions and rodent EAE quantitative trait loci and (2) linkage mapping in an F 10 (DA 3 PVG.AV1) rat advanced intercrossed line. The linkage mapping defines Eae18a to a 5-Mb region, which overlaps one intergenomic consensus region identified in silico. The combined approach confirms experimentally, for the first time, the accuracy of the in silico method. Moreover, the shared intersection between the results of both mapping techniques defines a 1.06-Mb region containing 13 candidate genes for the regulation of neuroinflammation in humans, rats, and mice.

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Section: Discussionmentioning

confidence: 99%

Section: Ultiple Sclerosis (Ms) Is a Chronic Inflammatorymentioning

confidence: 99%

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Definition of a 1.06-Mb Region Linked to Neuroinflammation in Humans, Rats and Mice

et al. 2006

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“…To identify a candidate gene, haplotype sharing analysis between different mouse strains may be used with so-called high density markers or by use of single nucleotide polymorphisms [79]. Other methods use comparative genomics technology analyzing sequence fragments from rat, mouse and human [80], or a combination of several techniques (gene expression profiling, gene mapping and QTL analysis) [81].…”

Section: Adoptive Transfer Eae (At-eae) Is Mediated By Intravenous Inmentioning

confidence: 99%

Mouse Models of Autoimmune Diseases

Marques

Müller²

2009

CDDT

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Significant progress has been made in past decades in our understanding of the basic mechanisms underlying autoimmune diseases. Nevertheless, many questions remain unanswered, in particular regarding the mechanisms at very early stages of these diseases. Reliable animal models are of crucial importance in basic research and may help us to understand central disease pathways. They are also indispensable for pre-clinical drug testing. Here we present and discuss two mouse models of rheumatoid arthritis and multiple sclerosis, respectively. In experimental studies using the models of collagen-induced arthritis and experimental autoimmune encephalomyelitis, the efficacy of new biological agents has been tested, which paved the way for clinical trials. A further interesting field where mouse models may provide valuable informations, is the identification of susceptibility genes for autoimmune diseases. Overall, in some instances studies with inbred strains may have an advantage over human studies, because environmental factors may easily be controlled and the genetic differences between different mouse strains are better characterized.

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“…1 Over 90% of the mouse and human genomes can be partitioned into corresponding regions of conserved synteny, and key pathways are most probably also conserved, opening the possibility to study the biology in mice and translate the results to the human situation. [2][3][4] Over 30 quantitative trait loci (QTL) for CIA in mice have been identified (listed at www.informatics.jax.org). However, the transition from QTL to QTG (quantitative trait gene) is not straightforward.…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling of arthritis using a QTL chip reveals a complex gene regulation of the Cia5 region in mice

et al. 2005

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One of the major quantitative trait loci (QTLs) associated with arthritis in crosses between B10.RIII and RIIIS/J mice is the Cia5 on chromosome 3. Early in the congenic mapping process it was clear that the locus was complex, consisting of several subloci with small effects. Therefore, we developed two novel strategies to dissect a QTL: the partial advanced intercross (PAI) strategy, with which we recently found the Cia5 region to consist of three loci, Cia5, Cia21 and Cia22, and now we introduce the QTL-chip strategy, where we have combined congenic mapping with a QTL-restricted expression profiling using a novel microarray design. The expression of QTL genes was compared between parental and congenic mice in lymph node, spleen and paw samples in five biological replicates and in dye-swapped experiments at three time points during the induction phase of arthritis. The QTL chip approach revealed 4 genes located in Cia21, differently expressed in lymph nodes, and 14 genes in Cia22, located within two clusters. One cluster contains six genes, differently expressed in spleen, and the second cluster contains eight genes, differently expressed in paws. We conclude the QTL-chip strategy to be valuable in the selection of candidate genes to be prioritized for further investigation.

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Intergenomic consensus in multifactorial inheritance loci: the case of multiple sclerosis

Cited by 18 publications

References 48 publications

Definition of a 1.06-Mb Region Linked to Neuroinflammation in Humans, Rats and Mice

Definition of a 1.06-Mb Region Linked to Neuroinflammation in Humans, Rats and Mice

Mouse Models of Autoimmune Diseases

Gene expression profiling of arthritis using a QTL chip reveals a complex gene regulation of the Cia5 region in mice

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