Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q

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.

Research on Topic Detection and Tracking for Online News Texts

“…In the topic identification process, the evaluation method in TDT2003 [29] is usually adopted. This method is to weigh and evaluate depending on the loss rate and false positive rate of the relevant reports in the topic detection and tracking results.…”

A cluster of multiple sclerosis cases in Lysvik in the Swedish county of Varmland

“…We propose that there later has been an accumulation of genes through inbreeding, and that a particular aggregation of genes disposing for MS has developed over time. There might also have been a single mutation responsible for the susceptibility to MS. A primary genetic analysis has been performed but the results are not conclusive, showing weak LOD scores for several loci (57), still somewhat in line with recent Finnish findings (44). Our genetic investigation is therefore now being expanded.…”

An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians

“…Variant chemokine expression could diminish or enhance the inflammatory response characteristic of MS. The majority of CC chemokine genes are located in a chromosomal region (17q11.2-12) that has shown suggestive linkage and association with MS in a number of genome wide screens [ 29 - 34 ]. Most recently, in a large genome wide linkage screen, no genome-wide significant results could be identified beyond the MHC [ 60 ].…”

“…This cluster spans slightly less than 2 Mb, and is split into two sub-clusters separated by a gap of 1.5 Mb. The 17q11.2-12 region has been implicated in genome-wide screens for linkage and association with MS [ 29 - 34 ], and in a meta-analysis of three genome screens, the most significant nonparametric linkage score was obtained for this region [ 35 ]. The 17q region is also syntenic to an EAE quantitative trait locus on chromosome 10, which includes a chemokine gene cluster [ 36 ], and non-synonymous polymorphisms in murine CCL1 , CCL2 and CCL12 were identified as candidates for the eae7 quantitative trait locus [ 37 ].…”