A whole genome screen for association with multiple sclerosis in Portuguese patients

Santos, Mónica; Pinto‐Basto, Jorge; Rio, Maria Edite; Sá, María José; Valença, A.; Sá, Alfredo; Dinis, José; Figueiredo, José Fernando de Castro; Almeida, L Bigotte de; Coelho, Isabel; Sawcer, Stephen; Setakis, Efrosini; Compston, Alastair; Sequeiros, Jorge; Maciel, Patrı́cia

doi:10.1016/j.jneuroim.2003.08.023

Cited by 13 publications

(7 citation statements)

References 17 publications

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“…GABRA3 regulates prolactin release which is a known immune response modulator [27]. Comparison of allele frequencies of microsatellites in pooled DNA samples of cases versus controls in a Northern European population has produced a number of significant associations [28][29][30][31][32][33][34]. However the interpretation of pooled DNA studies is problematic due to many sources of variance inherent to the technique.…”

Section: Discussionmentioning

confidence: 99%

Multiple sclerosis susceptibility and the X chromosome

et al. 2007

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Multiple sclerosis (MS) is a chronic autoimmune complex trait with strong evidence for a genetic component. A female gender bias is clear but unexplained and a maternal parent-of-origin effect has been described. X-linked transmission of susceptibility has been previously proposed, based on pedigree, association and linkage studies. We genotyped 726 relative pairs including 552 affected sib-pairs for 22 X-chromosome microsatellite markers and a novel dataset of 195 aunt-uncle/niece-nephew (AUNN) affected pairs for 18 markers. Parent-of-origin effects were explored by dividing AUNN families into likely maternal and paternal trait transmission. For the sib-pair dataset we were able to establish exclusion at a s ϭ1.9 for all markers using an exclusion threshold of LOD ՅϪ2. Similarly for the AUNN dataset, we established exclusion at AV ϭ1.9. For the combined dataset we estimate exclusion of ϭ1.6. We did not identify significant linkage in either the sib-pairs or the AUNN dataset nor when datasets were stratified for the presence/absence of the HLA-DRB1*15 allele or for paternal or maternal transmission. This comprehensive scrutiny of the X-chromosome suggests that it is unlikely to harbour an independent susceptibility locus or one which interacts with the HLA. Complex interactions including epigenetic ones, and masking by balanced polymorphisms are mechanisms not excluded by the approach taken. Multiple Sclerosis 2007; 13: 856-864. http://msj.sagepub.com

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Section: Discussionmentioning

confidence: 99%

Multiple sclerosis susceptibility and the X chromosome

et al. 2007

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“…The genome wide linkage analysis has been used to study the genetic component of MS since the mid 1990s. So far with the aid of this approach 19 studies have been carried out (Abdeen et al, 2006;Akesson et al, 2002;Ban et al, 2002;Bielecki et al, 2003;Broadley et al, 2001;Coraddu et al, 2001Coraddu et al, , 2003Ebers et al, 1996;Eraksoy et al, 2003;Goris et al, 2003;Haines et al, 1996;Hensiek et al, 2003;Kenealy et al, 2004;Kuokkanen et al, 1997;Liguori et al, 2003;Santos et al, 2003;Sawcer et al, 1996;Yeo et al, 2003). The linkage analysis is based on the detection of the highly polymorphic microsatellite repeats dispersed through the genome.…”

Section: Methods Used To Study Genetic Associations With Multifactorimentioning

confidence: 99%

Genetics of multiple sclerosis today

et al. 2016

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Multiple sclerosis is a common multifactorial disease in which the etiology of the interaction between external factors and structural specificities of a large number of genes plays an important role. Iden tification of the risk factors for multiple sclerosis and the development of an integrated pathogenesis model is a challenging task for neurology. The goal of the current review is to describe current approaches to studying the genetics of multifactorial diseases on the whole and multiple sclerosis in particular. Basic approaches to the design of the genetic epidemiological studies are described. Towards this end we discuss the gene candi date and the whole genome methods of studying genetic associations, the statistical approaches used to com bine the diverse data, namely, meta analysis of the results of different studies, analysis of the association with groups of functionally related genes, and comparison of the genetic bases of the diseases with similar patho genesis.

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“…In total, the GAMES collaborative screened 19 casecontrol cohorts and 10 trio family based cohorts (Sawcer and Compston, 2003) as described in the original publications: Australia (Ban et al, 2003), Belgium (Goris et al, 2003), Finland (Laaksonen et al, 2003), France (Alizadeh et al, 2003), Germany1 (Goedde et al, 2002), Germany2 (Weber et al, 2003), Hungary (Rajda et al, 2003), Iceland (Jonasdottir et al, 2003), Ireland (Heggarty et al, 2003), Italy (Liguori et al, 2003), Poland (Bielecki et al, 2003), Portugal1 (Santos et al, 2003), Portugal2 (Martins Silva et al, 2003, Sardinia (Coraddu et al, 2003), Scandinavia (Harbo et al, 2003), Spain (Goertsches et al, 2003), Turkey (Eraksoy et al, 2003) and UK (Sawcer et al, 2002). Table 1 summarizes the number of markers successfully analyzed in each cohort studied, as well as the number of samples in each pool.…”

Section: The Games Screensmentioning

confidence: 99%

Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans

Ban¹,

Booth²,

Heard³

et al. 2006

Journal of Neuroimmunology

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By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.

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A whole genome screen for association with multiple sclerosis in Portuguese patients

Cited by 13 publications

References 17 publications

Multiple sclerosis susceptibility and the X chromosome

Multiple sclerosis susceptibility and the X chromosome

Genetics of multiple sclerosis today

Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans

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