European Journal of Human Genetics, April 2002, vol. 10,
no. 4, pp. 271-275(5)
He B.; Giedraitis V.; Ligers A.; Binzer M.; Andersen P.M.; Forsgren L.; Sandkuijl L.A.; Hillert J.; Correspondence: V Giedraitis*
Division of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden Department of Neurology, University hospital of Umeå, Umeå, Sweden Institute of Clinical Genetics, Erasmus University, Rotterdam and Department of Human Genetics, Leiden University, The Netherlands [*]Division of Neurology, Huddinge University Hospital, Karolinska Institutet, S-141 86 Huddinge, Sweden; Tel: +46 8 585 81927; Fax: +46 8 585 87080
Multiple sclerosis (MS) is a chronic inflammatory disease resulting in demyelination in the central nervous system (CNS).
Increasing evidence supports that genetic factors confer susceptibility to MS.
One locus, the HLA complex (6p21), has been identified as important in MS, but no other loci have been clearly implicated, neither by a candidate gene approach, nor by a genomic screen strategy.
Here, we studied a genetically isolated population in the northern-most part of Sweden, which demonstrates a high incidence of MS, using haplotype sharing analysis.
Genealogical analysis demonstrated that 22 MS patients originate from a single common ancestral couple in the eighteenth century.
Five affected individuals from four nuclear families were selected for an initial genomic screen with 390 microsatellite markers.
Seven shared haplotypes in six different chromosomal regions were observed.
After genotyping for these haplotypes with the same and additional markers in 15 MS patients and healthy relatives, some portion of a conserved haplotype spanning 10 cM at 17p11 was found to be shared by 12 of 15 affected individuals.
The statistical analysis revealed a significant excess of transmission of alleles of three markers to affected individuals (P<0.05) by the transmission/disequilibrium test (TDT).
An identical four-marker haplotype was shared by six of 15 patients (40%; P<0.01).
Surprisingly, DR-typing revealed no significant sharing of the HLA region.
In conclusion, our data suggests a novel susceptibility gene for MS in chromosome 17p11.