Allogenotypes defined by short DQα and DQβ cDNA probes correlate with and define splits of HLA-DQ serological specificities

Bidwell, J. L.; Bidwell, Elizabeth A.; Laundy, G. J.; Klouda, P. T.; Bradley, B. A.

doi:10.1016/0161-5890(87)90026-5

Cited by 56 publications

(19 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We report that nine of 43 patients showed atypical associations, none of which have been previously described either in Caucasian or in non-Caucasian populations (Bidwell, 1988;Bidwell et al, 1988b); detection of these anomalous associations may have been facilitated by our use of short class I1 probes that simplify interpretation of allelespecific banding patterns (Bidwell et al, 1987). The most striking aberrant association was the finding of three different DQa allogenotypes in two patients in association with DR2,4, DQPlb, 3a allogenotypes.…”

Section: Hla Polymorphism In Multiple Sclerosis 51mentioning

confidence: 79%

See 1 more Smart Citation

HLA‐DRβ, ‐DQα, and ‐DQβ restriction fragment length polymorphisms in multiple sclerosis

Haegert

Michaud

Schwab

et al. 1989

J of Neuroscience Research

View full text Add to dashboard Cite

Restriction fragment length polymorphism (RFLP) studies were performed on DNA from unrelated Caucasian patients with multiple sclerosis (MS) using cDNA probes to the HLA class II genes DR beta, DQ alpha, and DQ beta. In a study of 34 patients and 34 controls who were not matched for DR type, we found that the DQ beta allele-specific RFLP or allogenotype, termed DQ beta lb, which corresponds at the molecular level to the DQwl serotype, is preferentially associated with MS. A significant disease association with DR2 was demonstrated by serology but this was not confirmed using DR2/Dw2-specific RFLPs. We suggest that DQ beta lb is largely responsible for HLA-associated susceptibility to MS and that the apparent MS-DR2 serological association is due to the strong linkage disequilibrium between DR2 and DQ beta lb. Homozygosity of one of the two allelic bands of the DX alpha gene, usually termed the DX alpha lower (DX alpha L) band (which cross-hybridizes with the DQ alpha probe), correlated with reduced susceptibility to MS. Similarly a 5.3 kb band identified by the DQ alpha probe in Mspl digests showed a negative correlation with MS. In an analysis of 27 DR2+ controls and 26 DR2+ patients it was found that these individuals all had DR2/Dw2-specific RFLPs and all had identical DR2/Dw2-associated DQ beta (DQ beta lb) and DQ alpha (DQ alpha lb) allogenotypes. We detected no polymorphisms of DR beta, DQ alpha, or DQ beta genes among the DR2+ MS patients which distinguished them from normals.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Hla Polymorphism In Multiple Sclerosis 51mentioning

confidence: 79%

“…Because of multiple comparisons using HLA class I1 allele-specific RFLPs (Table I), we adjusted the a level (a = 0.05) by doing each test at an a' = a divided by the number of (Bidwell et al, 1987;Cohen et al, 1985;Trowsdale et al, 1985;M. Howell, Tenovus, Southampton General Hospital, England, personal communication).…”

Section: Discussionmentioning

confidence: 99%

HLA‐DRβ, ‐DQα, and ‐DQβ restriction fragment length polymorphisms in multiple sclerosis

Haegert

Michaud

Schwab

et al. 1989

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…termed pl I P l (Larhammar ct al., 1982); and 3) a 900 bp DQa probe termed pDCHl (Auffray et al, 1984; for further details see Bidwell et al, 1987;Haegert et al, 1989). DNA probes were labelled with 32P dCTP by using the random priming method of Feinberg and Vogelstein (1983).…”

Section: Dna Probes Hybridization and Autoradiographymentioning

confidence: 99%

Multiple sclerosis and HLA class II susceptibility and resistance genes

Haegert

Michaud

Schwab

et al. 1990

J of Neuroscience Research

View full text Add to dashboard Cite

Probes to the HLA class II genes DR beta, DQ beta, and DQ alpha were used to study DNA from unrelated Caucasian multiple sclerosis (MS) patients by sequential restriction fragment length polymorphism (RFLP) analysis in Taq 1 restriction enzyme digests. Comparison of 104 patients and 108 controls, who were not matched for DR type, has identified for the first time a linked series of allele-specific RFLPs or allogenotypes which form an extended haplotype that is preferentially associated with MS. These allogenotypes include DRw15 or DR2(15); DQ beta lb, which corresponds at the DNA level to the DQwl(DQw6) serotype; a DQA1 allogenotype termed DQ alpha lb; and a 2.2 kb DX (DQA2) allogenotype termed DX alpha U (DQA2U). The role of HLA class II genes in susceptibility to MS was found to be complex. First, 23 of 104 MS patients showed DR-DQ linkages which were not observed in our control population. We suggest these anomalous associations may be important in the pathogenesis of MS. Second, homozygosity of a 2.0 kb DX (DQA2) gene, termed DX alpha L (DQA2L), showed a strong negative association with MS. DX alpha L (DQA2L) is in strong linkage disequilibrium with DR1, 5(w11) 7, and a subset of DR4, all of which also showed a negative association with MS. Since DX alpha L (DQA2L) does not code for any known product, DR1, 5(11), 4, and 7 become candidates for disease resistance genes.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…It has been proposed that PCP MS and R/R MS may be separate disease entities (6) since they differ with respect to epidemiology (6), age at onset (4, 5, 7), initial symptoms (4,6), prognosis with regard to degree of disability (4,7) and to mortality (8), and response to immunosuppression (9). Efforts to differentiate between PCP MS and R/R MS by serological HLA class II typing have yielded divergent and inconclusive results (10)(11)(12) (16)(17)(18).…”

mentioning

confidence: 99%

“…Two 5-min washes at room temperature in 2x SSC/0.5% SDS were followed by two 30-min high-stringency washes at 60°C in 0.lx SSC/0.1% SDS. Membranes were autoradiographed (X-Omat AR5, Kodak) with intensifying screens for 2-5 days at -70°C, and RFLP patterns were analyzed (16)(17)(18).…”

mentioning

confidence: 99%

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

Olerup

Hillert

Fredrikson

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

220

View full text Add to dashboard Cite

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes.Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotpe. In addition, primarily chronic progressive MS was positively associated with theDQBl restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQBI allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQBI allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers ofeach clinical form ofMS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS (4,5); i.e., the disease has a continuous progressive evolution from onset. It has been proposed that PCP MS and R/R MS may be separate disease entities (6) since they differ with respect to epidemiology (6), age at onset (4, 5, 7), initial symptoms (4, 6), prognosis with regard to degree of disability (4, 7) and to mortality (8), and response to immunosuppression (9 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

show abstract

Allogenotypes defined by short DQα and DQβ cDNA probes correlate with and define splits of HLA-DQ serological specificities

Cited by 56 publications

References 14 publications

HLA‐DRβ, ‐DQα, and ‐DQβ restriction fragment length polymorphisms in multiple sclerosis

HLA‐DRβ, ‐DQα, and ‐DQβ restriction fragment length polymorphisms in multiple sclerosis

Multiple sclerosis and HLA class II susceptibility and resistance genes

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

Contact Info

Product

Resources

About