Linkage regions in this table are based on the whole genome linkage screen meta-analyses by Hermanowski et al. (2007), in particular the results summarized in Table 2 of that paper. Meta-analyses (using the Genome Search Meta-Analysis [GSMA] method) were performed on data from a total of 10 whole genome linkage studies published at the time of inclusion (end of 2005). Note that six studies were excluded by Hermanowski et al. (2007) due to overlap with subsequent studies (Haines et al. [1996], Sawcer et al. [1996], Ebers et al. [1996], Haines et al. [2002]), or due to other reasons (Coraddu et al. [2001], Lucotte et al. [2002]). Note that the meta-analyses by Hermanowski et al. (2007) did not include candidate region linkage studies investigating only small genomic regions, or genome-wide association studies. Please consult the paper by Hermanowski et al. (2007) for more details on inclusion and exclusion criteria and methodology. The study by Hermanowski et al. (2007) analyzed the largest number of whole genome linkage screens. Note that three meta-analyses (Wise et al. [1999], The Transatlantic Multiple Sclerosis Genetics Cooperative [2001], GAMES [2003]) had been performed prior to the Hermanowski study, but owing to their earlier inception made use of fewer independent datasets. For more details please consult the corresponding publications. A complete list of all genome wide linkage studies in MS can be found below in the reference section.

Note that since the publication of Hermanowski et al. (2007), several additional whole genome linkage screens have been performed (Haghighi et al. [2006], Willer et al. [2007], Dyment et al. [2008], Pitzalis et al. [2008]) some of which replicated 6p21, 18p11, and 20p12 as putative MS linkage regions, and/or some of which reported suggestive linkage with other loci (1q42, 4q32, 6q12, 12q24, 19q13) that require further replication and meta-analysis.

On the chromosome overview pages of MSGene, the approximate chromosomal intervals of these loci are indicated by a red vertical line (see example [insert link here to chromosome 6]). "Initial study" refers to the publication which first identified a particular chromosomal region to show evidence for genetic linkage using a whole genome approach.

References

Akesson, E., A. Oturai, et al. (2002). "A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis." Genes Immun 3(5): 279-85. [PubMed ID: 12140746]

Ban, M., G. J. Stewart, et al. (2002). "A genome screen for linkage in Australian sibling-pairs with multiple sclerosis." Genes Immun 3(8): 464-9. [PubMed ID: 12486604]

Broadley, S., S. Sawcer, et al. (2001). "A genome screen for multiple sclerosis in Italian families." Genes Immun 2(4): 205-10. [PubMed ID: 11477475]

Coraddu, F., S. Sawcer, et al. (2001). "A genome screen for multiple sclerosis in Sardinian multiplex families." Eur J Hum Genet 9(8): 621-6. [PubMed ID: 11528508]

Dyment, D. A., M. Z. Cader, et al. (2008). "A genome scan in a single pedigree with a high prevalence of multiple sclerosis." J Neurol Neurosurg Psychiatry 79(2): 158-62. [PubMed ID: 17550985]

Dyment, D. A., A. D. Sadovnick, et al. (2004). "An extended genome scan in 442 Canadian multiple sclerosis-affected sibships: a report from the Canadian Collaborative Study Group." Hum Mol Genet 13(10): 1005-15. [PubMed ID: 15069025]

Ebers, G. C., K. Kukay, et al. (1996). "A full genome search in multiple sclerosis." Nat Genet 13(4): 472-6. [PubMed ID: 8696345]

Eraksoy, M., M. Kurtuncu, et al. (2003). "A whole genome screen for linkage in Turkish multiple sclerosis." J Neuroimmunol 143(1-2): 17-24. [PubMed ID: 14575909] GAMES (2003). "A meta-analysis of whole genome linkage screens in multiple sclerosis." J Neuroimmunol 143(1-2): 39-46. [PubMed ID: 14575912]

Haghighi, S., O. Andersen, et al. (2006). "A linkage study in two families with multiple sclerosis and healthy members with oligoclonal CSF immunopathy." Mult Scler 12(6): 723-30. [PubMed ID: 17262999]

Haines, J. L., Y. Bradford, et al. (2002). "Multiple susceptibility loci for multiple sclerosis." Hum Mol Genet 11(19): 2251-6. [PubMed ID: 12217953]

Haines, J. L., M. Ter-Minassian, et al. (1996). "A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group." Nat Genet 13(4): 469-71. [PubMed ID: 8696344]

Hensiek, A. E., R. Roxburgh, et al. (2003). "Updated results of the United Kingdom linkage-based genome screen in multiple sclerosis." J Neuroimmunol 143(1-2): 25-30. [PubMed ID: 14575910]

Hermanowski, J., E. Bouzigon, et al. (2007). "Meta-analysis of genome-wide linkage studies for multiple sclerosis, using an extended GSMA method." Eur J Hum Genet 15(6): 703-10. [PubMed ID: 17377519]

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Kuokkanen, S., M. Gschwend, et al. (1997). "Genomewide scan of multiple sclerosis in Finnish multiplex families." Am J Hum Genet 61(6): 1379-87. [PubMed ID: 9399895]

Lucotte, G. L. (2002). "Confirmation of a gene for multiple sclerosis (MS) to chromosome region 19q13.3." Genet Couns 13(2): 133-8. [PubMed ID: 12150212]

Modin, H., T. Masterman, et al. (2003). "Genome-wide linkage screen of a consanguineous multiple sclerosis kinship." Mult Scler 9(2): 128-34. [PubMed ID: 12708807]

Pitzalis, M., P. Zavattari, et al. (2008). "Genetic loci linked to type 1 diabetes and multiple sclerosis families in Sardinia." BMC Med Genet 9: 3. [PubMed ID: 18205952]

Sawcer, S., M. Ban, et al. (2005). "A high-density screen for linkage in multiple sclerosis." Am J Hum Genet 77(3): 454-67. [PubMed ID: 16080120]

Sawcer, S., H. B. Jones, et al. (1996). "A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22." Nat Genet 13(4): 464-8. [PubMed ID: 8696343]

TMSGC (2001). "A meta-analysis of genomic screens in multiple sclerosis. The Transatlantic Multiple Sclerosis Genetics Cooperative." Mult Scler 7(1): 3-11. [PubMed ID: 11321191]

Willer, C. J., D. A. Dyment, et al. (2007). "A genome-wide scan in forty large pedigrees with multiple sclerosis." J Hum Genet 52(12): 955-62. [PubMed ID: 18000641]

Wise, L. H., J. S. Lanchbury, et al. (1999). "Meta-analysis of genome searches." Ann Hum Genet 63(Pt 3): 263-72. [PubMed ID: 10738538]