학술논문

Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q.
Document Type
Article
Source
Genes & Immunity. Dec2003, Vol. 4 Issue 8, p559-563. 5p.
Subject
*MULTIPLE sclerosis risk factors
*GENETICS of disease susceptibility
*HUMAN chromosome abnormalities
*HLA histocompatibility antigens
*GENOTYPE-environment interaction
*ENVIRONMENTALLY induced diseases
*MEDICAL genetics
Language
ISSN
1466-4879
Abstract
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.Genes and Immunity (2003) 4, 559-563. doi:10.1038/sj.gene.6364024 [ABSTRACT FROM AUTHOR]