title: Genetic fixity in the human major histocompatibility complex and block size diversity in the class I region including HLA-E.
abstract: BACKGROUND
  The definition of human MHC class I haplotypes through association of HLA-A, HLA-Cw and HLA-B has been used to analyze ethnicity, population migrations and disease association.
  
  
  RESULTS
  Here, we present HLA-E allele haplotype association and population linkage disequilibrium (LD) analysis within the ~1.3 Mb bounded by HLA-B/Cw and HLA-A to increase the resolution of identified class I haplotypes. Through local breakdown of LD, we inferred ancestral recombination points both upstream and downstream of HLA-E contributing to alternative block structures within previously identified haplotypes. Through single nucleotide polymorphism (SNP) analysis of the MHC region, we also confirmed the essential genetic fixity, previously inferred by MHC allele analysis, of three conserved extended haplotypes (CEHs), and we demonstrated that commercially-available SNP analysis can be used in the MHC to help define CEHs and CEH fragments.
  
  
  CONCLUSIONS
  We conclude that to generate high-resolution maps for relating MHC haplotypes to disease susceptibility, both SNP and MHC allele analysis must be conducted as complementary techniques.
authors: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA. Viviana_romero@dfci.harvard.edu <Viviana_romero@dfci.harvard.edu>
authors: Viviana
authors: V
authors: Romero
authors: Charles E
authors: CE
authors: Larsen
authors: Jonathan S
authors: JS
authors: Duke-Cohan
authors: Edward A
authors: EA
authors: Fox
authors: Tatiana
authors: T
authors: Romero
authors: Olga P
authors: OP
authors: Clavijo
authors: Dolores A
authors: DA
authors: Fici
authors: Zaheed
authors: Z
authors: Husain
authors: Ingrid
authors: I
authors: Almeciga
authors: Dennis R
authors: DR
authors: Alford
authors: Zuheir L
authors: ZL
authors: Awdeh
authors: Joaquin
authors: J
authors: Zuñiga
authors: Lama
authors: L
authors: El-Dahdah
authors: Chester A
authors: CA
authors: Alper
authors: Edmond J
authors: EJ
authors: Yunis
mesh_terms: D000483:Alleles; D002460:Cell Line; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D005787:Gene Frequency; D005805:Genes, MHC Class I; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D000097625:HLA-E Antigens
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens