Conserved extended haplotypes of the major histocompatibility complex: further characterization

Dorak, M. Tevfik; Shao, Wenshuo; Machulla, Helmut K.G.; Lobashevsky, Elena; Tang, Jianming; Park, M H; Kaslow, Richard A.

doi:10.1038/sj.gene.6364315

Cited by 68 publications

(79 citation statements)

References 128 publications

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“…All the extended haplotypes present in at least two independent chromosomes or a formerly approved AH 16 contained exactly one copy of the functional CYP21A2 gene; however, it is noteworthy that the rare haplotype AH47.1 characterized by a CYP21A2/CYP21A1P chimera gene (thus complete CYP21A2 deletion) 17 was not found in our samples.…”

Section: Determination Of Rccx and Mhc Haplotypesmentioning

confidence: 58%

“…Haplotypes were assigned as ancestral when they contained identical HLA-B, -DRB1 and -DQB1 alleles, CFB S4F, LTA 252 A4G and HSPA1B 1267 A4G polymorphisms and C4A/C4B GCNs as AHs characterized by an extensive study on International Histocompatibility Working Group (IHWG) reference cell lines. 16 Thus, 15 AHs (or CEHs) were found in our samples, and 14 additional extended haplotypes occurred in at least two independent copies with 100% match of these polymorphisms (repeatedly occurring haplotypes never differed in TNF À 308 G4A and AGER À 429 T4C SNPs either) ( Table 3). Considering all 184 haplotypes examined, 51 (27.7%) belonged to a recognized AH, 34 (18.5%) did not belong to an AH but occurred repeatedly in the study population, whereas the remaining 99 (53.8%) were found in a single copy only and did not belong to any recognized AH.…”

Section: Determination Of Rccx and Mhc Haplotypesmentioning

confidence: 76%

“…Although in some cases HLA alleles were examined together with RCCX variants earlier, 25 no extensive investigation has been published yet. As even certain formerly recognized ancestral MHC haplotypes differ only in polymorphisms other than HLA alleles, 16 we analyzed five SNPs as well. Three (CFB S4F, LTA 252 A4G and HSPA1B 1267 A4G) of those were also involved in the mentioned study on IHWG reference cell lines, 16 whereas the other two (TNF À 308 G4A and AGER À 429 T4C) were chosen because they formerly proved to be useful tools for haplotype tagging.…”

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 99%

“…As even certain formerly recognized ancestral MHC haplotypes differ only in polymorphisms other than HLA alleles, 16 we analyzed five SNPs as well. Three (CFB S4F, LTA 252 A4G and HSPA1B 1267 A4G) of those were also involved in the mentioned study on IHWG reference cell lines, 16 whereas the other two (TNF À 308 G4A and AGER À 429 T4C) were chosen because they formerly proved to be useful tools for haplotype tagging. 26,27 As expected, chromosomes with identical extended haplotypes tend to carry the same RCCX structures.…”

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 99%

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Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

et al. 2012

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The human RCCX is a common multiallelic copy number variation locus whose number of segments varies between one and four in a chromosome. The monomodular form normally comprises four functional genes, but in duplicated RCCX segments generally only the gene-encoding complement component C4 produces a protein. C4 genes can code either for a C4A or a C4B isotype protein and exhibit dichotomous size variation. Distinct RCCX variants show association with numerous diseases; however, identification of the basis of these associations is often challenging, not least because the RCCX is localized in the major histocompatibility complex (MHC) region, a genomic area characterized by exceedingly long-range linkage disequilibrium. Here we present a detailed analysis on RCCX variants and their relationship with so-called 'ancestral' or 'conserved extended' MHC haplotypes in healthy Caucasians. In addition to former investigations, precise order and size of all C4A and C4B genes were determined even in trimodular RCCX structures. Considering C4 copy numbers, length, isotype specificity and CYP21A2 copy numbers, we have identified 15 distinct RCCX variants and described the RCCX structures involved in 29 repeatedly occurring MHC haplotypes. The findings should become a useful tool for future RCCX-and MHC-related disease association studies.

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Section: Determination Of Rccx and Mhc Haplotypesmentioning

confidence: 58%

Section: Determination Of Rccx and Mhc Haplotypesmentioning

confidence: 76%

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 99%

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 99%

See 2 more Smart Citations

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

et al. 2012

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“…Cw*05 is a marker of three ancestral or conserved extended HLA haplotypes, [14][15][16] As stated above, the A*02-Cw*05 combination is carried by two HLA ancestral haplotypes (44.1 and 18.3). However, as the individuals included in this study were not typed for HLA-B and other HLA markers, from our data it is not possible to conclude whether the enhanced MS-protective effect of the A*02-Cw*05 combination is due to an haplotype effect (that is the presence of a primarily associated protective factor carried by the extended haplotype marked by A*02 and Cw*05) or to a direct interactive role of the two markers.…”

Section: Hla-class I Markers Involved In Ms Susceptibility L Bergamasmentioning

confidence: 99%

HLA-class I markers and multiple sclerosis susceptibility in the Italian population

et al. 2009

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Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR ¼ 0.61; 95% confidence intervals, CI ¼ 0.51-0.72, Po10 À9 ), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI ¼ 0.13-0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI ¼ 0.58-0.83) with a significant (P ¼ 4.94 Â 10 À5 ) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR ¼ 3.89, P ¼ 0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively.

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Relationship of polymorphisms located in tumor necrosis factor region and HLA loci among Croatians

Štingl

Grubić

Car

et al. 2008

American J Hum Biol

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Polymorphism of TNFa, TNFb, and TNFd microsatellites, linkage disequilibrium (LD) within TNF region as well as relationship of TNF microsatellites with alleles at HLA-A, -B, and -DRB1 loci was investigated on a sample of 160 Croatians, previously typed for HLA-A, -B, and -DRB1 loci. Analysis of the relationship of TNF alleles and HLA specificities revealed that very strong associations exist between TNFa2, TNFb3, and TNFd2 alleles and HLA-A*01, -B*08, and -DRB1*03 specificities, therefore placing them in the 8.1 ancestral haplotype. Similar findings were observed for TNFa11, TNFb4, and TNFd4 alleles and HLA specificities, which are a part of the 7.1 ancestral haplotype. Finally, multiple associations with significant P-values were also observed between TNFa10, TNFb4, and TNFd4 microsatellite alleles and HLA-A*02, -B*18, -DRB1*11 specificities which form the 18.3 ancestral hapolotype.

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Conserved extended haplotypes of the major histocompatibility complex: further characterization

Cited by 68 publications

References 128 publications

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

HLA-class I markers and multiple sclerosis susceptibility in the Italian population

Relationship of polymorphisms located in tumor necrosis factor region and HLA loci among Croatians

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