ArticleAmerican journal of human genetics2002
Genetic dissection of the human leukocyte antigen region by use of haplotypes of Tasmanians with multiple sclerosis.
Article in American journal of human genetics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 93 citations in OpenAlex.
- Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study.BMJ (Clinical research ed.) · 2003Trial
- Integrating the Ribonucleic Acid Sequencing Data From Various Studies for Exploring the Multiple Sclerosis-Related Long Noncoding Ribonucleic Acids and Their Functions.Frontiers in genetics · 2019Article
- Community engagement for big epidemiology: deliberative democracy as a tool.Journal of personalized medicine · 2014Article
- Adaptive immune responses in CNS autoimmune disease: mechanisms and therapeutic opportunities.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2013Review
- Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.PloS one · 2013Article
- The genetics of multiple sclerosis: an up-to-date review.Immunological reviews · 2012Review
- Revealing the genetic basis of multiple sclerosis: are we there yet?Current opinion in genetics & development · 2011Review
- The genetic aspects of multiple sclerosis.Annals of Indian Academy of Neurology · 2009Article
- Epistasis among HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci determines multiple sclerosis susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Genotype-Phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures.Brain : a journal of neurology · 2009Article
- The complex genetics of multiple sclerosis: pitfalls and prospects.Brain : a journal of neurology · 2008Review
- Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians.Genes and immunity · 2008Article
- A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy.Genes and immunity · 2008Article
- The spectrum of multiple sclerosis.Current allergy and asthma reports · 2007Review
- Variation of the myelin oligodendrocyte glycoprotein gene is not primarily associated with multiple sclerosis in the Sardinian population.BMC genetics · 2007Article
- Analysis of extended HLA haplotypes in multiple sclerosis and narcolepsy families confirms a predisposing effect for the class I region in Tasmanian MS patients.Immunogenetics · 2007Article
- A second major histocompatibility complex susceptibility locus for multiple sclerosis.Annals of neurology · 2007Article
- Asthma onset prior to multiple sclerosis and the contribution of sibling exposure in early life.Clinical and experimental immunology · 2006Article
- Contrasting linkage-disequilibrium patterns between cases and controls as a novel association-mapping method.American journal of human genetics · 2006Article
- Detecting genome wide haplotype sharing using SNP or microsatellite haplotype data.Human genetics · 2006Article
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Association of multiple sclerosis (MS) with the human leukocyte antigen (HLA) class II haplotype DRB1*1501-DQB1*0602 is the most consistently replicated finding of genetic studies of the disease. However, the high level of linkage disequilibrium (LD) in the HLA region has hindered the identification of other loci that single-marker tests for association are unlikely to resolve. In order to address this issue, we generated haplotypes spanning 14.754 Mb (5 cM) across the entire HLA region. The haplotypes, which were inferred by genotyping relatives of 152 patients with MS and 105 unaffected control subjects of Tasmanian ancestry, define a genomic segment from D6S276 to D6S291, including 13 microsatellite markers integrated with allele-typing data for DRB1 and DQB1. Association to the DRB1*1501-DQB1*0602 haplotype was replicated. In addition, we found that the class I/extended class I region, defined by a genomic segment of approximately 400 kb between MOGCA and D6S265, harbors genes that independently increase risk of, or provide protection from, MS. Log-linear modeling analysis of constituent haplotypes that represent genomic regions containing class I (MOGCA-D6S265), class III (TNFa-TNFd-D6S273), and class II (DRB1-DQB1) genes indicated that having class I and class II susceptibility variants on the same haplotype provides an additive effect on risk. Moreover, we found no evidence for a disease locus in the class III region defined by a 150-kb genomic segment containing the TNF locus and 14 other genes. A global overview of LD performed using GOLD identified two discrete blocks of LD in the HLA region that correspond well with previous findings. We propose that the analysis of haplotypes, by use of the types of approaches outlined in the present article, should make it possible to more accurately define the contribution of the HLA to MS.
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