Conserved extended haplotypes of the major histocompatibility complex: further characterization.
Since the complete sequencing of a human major histocompatibility complex (MHC) haplotype, interest in non-human leucocyte antigen (HLA) genes encoded in the MHC has been growing. Non-HLA genes, which outnumber the HLA genes, may contribute to or account for HLA and disease associations. Most information on non-HLA genes has been obtained in separate studies of individual loci. To comprehensively address polymorphisms of relevant non-HLA genes in 'conserved extended haplotypes' (CEH), we investigated 101 International Histocompatibility Workshop reference cell lines and nine additional anonymous samples representing all 37 unambiguously characterized CEHs at MICA, NFKBIL1, LTA, NCR3, AIF1, HSPA1A, HSPA1B, BF, NOTCH4 and a single nucleotide polymorphism (SNP) at HLA-DQA1 as well as MICA, NOTCH4, HSPA1B and all five tumour necrosis factor short tandem repeat (STR) polymorphisms. This work (1) provides an extensive catalogue of MHC polymorphisms in all CEHs, (2) unravels interrelationships between HLA and non-HLA haplotypical lineages, (3) resolves reported typing ambiguities and (4) describes haplospecific markers for a number of CEHs. Analysis also identified a DQA1 SNP and segments containing MHC class III polymorphisms that corresponded with class II (DRB3 and DRB4) lineages. These results portray the MHC where lineages containing non-HLA and HLA variants in linkage disequilibrium may operate in concert and can guide more thorough design and interpretation of HLA-disease relationships.
Dorak
M T
MT
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. dorak@openlink.org
Shao
W
W
Machulla
H K G
HK
Lobashevsky
E S
ES
Tang
J
J
Park
M H
MH
Kaslow
R A
RA
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008840:Microfilament Proteins; D055628:Natural Cytotoxicity Triggering Receptor 3; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000074562:Receptor, Notch4; D011971:Receptors, Immunologic / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics; D020080:Tandem Repeat Sequences; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D020413:3' Untranslated Regions; C112986:AIF1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D015235:HLA-B Antigens; C088036:HLA-B67 antigen; D006683:HLA-DQ Antigens; D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008233:Lymphotoxin-alpha; C099187:MHC class I-related chain A; D008840:Microfilament Proteins; C431710:NCR3 protein, human; C120111:NFKBIL1 protein, human; C106075:NOTCH4 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011971:Receptors, Immunologic; D051880:Receptors, Notch; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha