liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q
Division of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
Division of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
Show others and affiliations
2003 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 4, no 8, 559-563 p.Article in journal (Refereed) Published
Abstract [en]

Epidemiological studies show that susceptibility to multiple sclerosis (MS) has a strong genetic component, but apart from the HLA gene complex, additional genetic factors have proven difficult to map in the general population. Thus, localized populations, where MS patients are assumed to be more closely related, may offer a better opportunity to identify shared chromosomal regions. We have performed a genome-wide scan with 834 microsatellite markers in a data set consisting of 54 MS patients and 114 healthy family members. A group of families from a small village were possible to track back to common ancestors living in the 17th century. We used single marker- and haplotype-based transmission disequilibrium test (TDT) analysis and nonparametric linkage analysis to analyze genotyping data. Regions on chromosomes 2q23–31, 6p24–21, 6q25–27, 14q24–32, 16p13–12 and 17q12–24 were found to be in transmission disequilibrium with MS. Strong transmission disequilibrium was detected in 14q24–32, where several dimarker haplotypes were in transmission disequilibrium in affected individuals. Several regions showed modest evidence for linkage, but linkage and TDT were both clearly positive only for 17q12–24. All patients and controls were also typed for HLA class II genes; however, no evidence for a gene–gene interaction was observed.

Place, publisher, year, edition, pages
2003. Vol. 4, no 8, 559-563 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-27719DOI: 10.1038/sj.gene.6364024Local ID: 12457OAI: oai:DiVA.org:liu-27719DiVA: diva2:248271
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Epidemiological and genetic studies of muliple sclerosis with focus on the Swedish county of Värmland
Open this publication in new window or tab >>Epidemiological and genetic studies of muliple sclerosis with focus on the Swedish county of Värmland
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this study was to perform detailed investigations of a presumed high-risk area, namely the county of Värmland, to see if previous results from our group indicating a high frequency of multiple sclerosis (MS) could be confirmed. We soon identified an aggregation of MS cases in the parish of Lysvik located in the north of Värmland and initiated epidemiological and genetical analyses of the population. We also extended our genetic research to include studies of a possible association between MS immunopathic trait and the MS susceptibility gene HLA-DR(2)15 type, but in another geographic area.

The onset-adjusted prevalence of MS in Värmland was 170/105 (95% CI: 154-185) in December 2002, which is higher than prevalence previously reported from other Swedish areas. There was a great variation in MS frequency between communities in Värmland. We found a persistently high occurrence of MS in Torsby and Sunne communities. In the community of Årjäng MS frequency had increased substantially since the previous study performed by our group.

Epidemiological analysis of a cluster of MS cases in Lysvik revealed 27 MS patients, of whom 23 were the descendants of a Finnish family originated from a common ancestor born in Savolaks in Finland in the 16th century and 18 had relatives with MS. Since this cluster was most likely to have a genetic basis (located in an area with a high inbreeding rate) the mode of MS inheritance was investigated. The linkage study using the genome-wide transmission disequilibrium test (TDT) provided several regions of interest, especially on chromosome 14q (14q24-31). The linkage peak on chromosome 17q was also confirmed by this study.

The frequency of the HLA-DR(2)15 allele was higher in healthy siblings of MS patients without MS immunopathic trait (MSIT) than in siblings with the trait, which provides further support for the hypothesis that MSIT and MS are two independent, albeit, synergistic conditions.

The prevalence study supports that Värmland County is a high-risk area. Furthermore, the aggregation of MS cases in Lysvik indicates a concentrated risk zone, possibly due to a combination of genetic, environmental and social risk factors. A widely and evenly spread environmental (i.e., infectious) agent together with cultural changes and industrialisation could possibly induce disease in subgroups of genetically more susceptible individuals. The evidence of linkage to chromosome 14 found in this study indicates that further genetic research is required.

Place, publisher, year, edition, pages
Linköping: Institutionen för nervsystem och rörelseorgan, 2006. 60 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 949
Keyword
Inborn genetic diseases, Genetic predisposition to disease, Genetic predisposition to disease, Cluster analysis, Muliple sclerosis, Pedigree
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-7444 (URN)91-85497-86-X (ISBN)
Public defence
2006-06-01, Elsa Brändströms sal, Södra ingången, plan 10, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Available from: 2006-09-27 Created: 2006-09-27 Last updated: 2012-10-23Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Callander, MargaritaLandtblom, Anne-Marie

Search in DiVA

By author/editor
Callander, MargaritaLandtblom, Anne-Marie
By organisation
NeurologyFaculty of Health Sciences
In the same journal
Genes and Immunity
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 59 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf