Journal ArticleDOI
A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2.
Satu Kuokkanen,Mats Sundvall,Joseph D. Terwilliger,Pentti J. Tienari,Juhani Wikström,Rikard Holmdahl,Ulf Pettersson,Leena Peltonen +7 more
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TLDR
Evidence is provided for a predisposing locus for MS on 5p14–p12, syntenic to the murine locus Eae, which is widely speculated to be a multifactorial disorder with a complex mode of inheritance.Abstract:
Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by multifocal damage of myelin in the central nervous system (CNS). The prevalence of this putative autoimmune disease is 0.1% in individuals of northern European origin. Family, adoption and twin studies implicate genetic factors in the aetiology. MS is widely speculated to be a multifactorial disorder with a complex mode of inheritance. Despite many studies of candidate genes, only an association with HLA-DR2-DQ6 has been generally detected, and the number of susceptibility genes remains unknown. The chronic variant of experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease in rodents, represents a relevant animal model for MS given the chronic relapsing disease course and inflammatory changes of CNS observed in these demyelinating disorders. Susceptibility to EAE is also influenced by the major histocompatibility complex (MHC). Human syntenic regions to murine loci predisposing to EAE were tested as candidate regions for genetic susceptibility of MS. Three chromosomal regions (1p22-q23, 5p14-p12 and Xq13.2-q22) were screened in 21 Finnish multiplex MS families most originating from a high risk region in western Finland. Several markers yielded positive lod scores on 5p14-p12, syntenic to the murine locus Eae2. Our data provide evidence for a predisposing locus for MS on 5p14-p12.read more
Citations
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Genetic Dissection of Complex Traits
TL;DR: The current state of the genetic dissection of complex traits is summarized in this paper, which describes the methods, limitations, and recent applications to biological problems, including linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses.
Journal ArticleDOI
Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases
Kevin G. Becker,Richard M. Simon,Joan E. Bailey-Wilson,Boris Freidlin,William E. Biddison,Henry F. McFarland,Jeffrey M. Trent +6 more
TL;DR: A majority (approximately 65%) of the human positive linkages map nonrandomly into 18 distinct clusters, which supports a hypothesis that, in some cases, clinically distinct autoimmune diseases may be controlled by a common set of susceptibility genes.
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Genetics of multiple sclerosis
TL;DR: To overcome the confounding effects of genetic complexity, MS genetic research needs to take advantage of clinical and epidemiological information to better homogenize study samples and shed some light on the mild to moderate susceptibility loci affecting the MS patient population.
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Identification of a Major Susceptibility Locus on Chromosome 6p and Evidence for Further Disease Loci Revealed by a Two Stage Genome-Wide Search in Psoriasis
Richard C. Trembath,R. Lee Clough,Jane L. Rosbotham,Jane L. Rosbotham,Andrew B. Jones,Richard D.R. Camp,Angela J. Frodsham,Julie Browne,Ruth C. Barber,Joseph D. Terwilliger,Joseph D. Terwilliger,G. Mark Lathrop,Jonathan Barker +12 more
TL;DR: The results of this genome wide analysis demonstrate that, at least in the population studied, a gene or genes located within the MHC and close to the class 1 HLA loci represent the major determinant of the genetic basis of psoriasis.
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Use of population isolates for mapping complex traits
TL;DR: A large number of population isolates have been targeted for mapping genes for complex diseases using haplotype signatures and the past successes with Mendelian disorders have prompted unprecedented interest among medical researchers in both the public and private sectors.
References
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Journal ArticleDOI
New diagnostic criteria for multiple sclerosis: guidelines for research protocols.
Charles M. Poser,Donald W. Paty,Labe C. Scheinberg,W I McDonald,F A Davis,George C. Ebers,Kenneth P. Johnson,William A. Sibley,Donald H. Silberberg,Wallace W. Tourtellotte +9 more
TL;DR: Today there is a need for more exact criteria than existed earlier in order to conduct therapeutic trials in multicenter programs, to compare epidemiological surveys, to evaluate new diagnostic procedures, and to estimate the activity of the disease process in MS.
Journal ArticleDOI
Genetic dissection of complex traits
TL;DR: This article synthesizes the current state of the genetic dissection of complex traits--describing the methods, limitations, and recent applications to biological problems.
Journal ArticleDOI
A comprehensive genetic map of the human genome based on 5,264 microsatellites
Colette Dib,Sabine Fauré,Cécile Fizames,Delphine Samson,N. Drouot,Alain Vignal,P Millasseau,S Marc,Jamilé Hazan,Eric Seboun,Mark Lathrop,Gabor Gyapay,Jean Morissette,Jean Morissette,Jean Weissenbach +14 more
TL;DR: The last version of the Généthon human linkage map is reported, which consists of 5,264 short tandem repeat polymorphisms with a mean heterozygosity of 70%.
Journal ArticleDOI
Strategies for multilocus linkage analysis in humans.
TL;DR: The results show that considerable economy and efficiency can be brought to the mapping endeavor by resorting to appropriate strategies of detecting linkage and by constructing the human genetic map on a common reference panel of families.
Genetic Dissection of Complex Traits
TL;DR: The current state of the genetic dissection of complex traits is summarized in this paper, which describes the methods, limitations, and recent applications to biological problems, including linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses.
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