Sharing of a conserved haplotype suggests a susceptibility gene for multiple sclerosis at chromosome 17p11

被引:13
作者
He, B
Giedraitis, V [1 ]
Ligers, A
Binzer, M
Andersen, PM
Forsgren, L
Sandkuijl, LA
Hillert, J
机构
[1] Huddinge Univ Hosp, Karolinska Inst, Div Neurol, S-14186 Huddinge, Sweden
[2] Karolinska Inst, Dept Med Biochem & Biophys, Div Matrix Biol, Stockholm, Sweden
[3] Univ Umea Hosp, Dept Neurol, S-90185 Umea, Sweden
[4] Erasmus Univ, Inst Clin Genet, Rotterdam, Netherlands
[5] Leiden Univ, Dept Human Genet, NL-2300 RA Leiden, Netherlands
关键词
chromosome; 17p; genomic screen; haplotype sharing; multiple sclerosis; susceptibility gene;
D O I
10.1038/sj.ejhg.5200802
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:271 / 275
页数:5
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