Hereditas (Beijing) (遗传) 2010/32:7 PP.685-693
In the present study, a high-resolute method for cloning and sequencing genomic full-length HLA-A and -B using 20 Chinese Han individuals was established. We detected 10 HLA-A allele sequences 4.2 kb in length and 6 HLA-B allele sequences 3.7 kb in length, and the sequences included all exons, all introns, 5′promoter, and 3′UTR of the two genes. All sixteen sequences have been submitted to GenBank and IMGT/HLA database. A*1153 is a novel allele, and the introns of B*151101 are firstly reported here. The 5′promoter and 3′UTR sequences of 5 HLA-A alleles and 2 HLA-B alleles are also firstly disclosed, and all other alleles have extended the genomic full length sequences released in IMGT/HLA database. The polymorphic structures of upper 5′promoter and downstream 3′UTR, which were uncovered in IMGT/HLA database, are firstly depicted in Chinese Han individuals. Twenty-six single nucleotide polymorphisms (SNPs) and one 3 bp-insertion/deletion (Indel) were located in the upper 5′promoter and 14 SNPs were located in the 3′UTR of HLA-A. In addition, five SNPs and one 1 bp-indel were located in the upper 5′promoter and 5 SNPs were located in the 3′UTR of HLA-B. Through analyzing the phylogenetic trees of 5′promoter, exons and 3′UTR of the two genes, we found that the evolution history of regulatory regions and exons is different between the two genes. The regulatory regions are tightly linked with exons in most of HLA-A alleles excluding A*24020101. On the contrary, recombinant events may occur frequently between regulatory regions and exons in most HLA-B alleles.
 Hughes AL, Nei M. Pattern of nucleotide substitution at MHC class I loci reveals overdominant selection. Nature, 1988, 335(6186): 167-170.
 Hughes AL, Yeager M. Natural selection at major histo-compatibility complex loci of vertebrates. Annu Rev Genet, 1998, 32: 415-435.
 Gao X, Nelson GW, Karacki P, Martin MP, Phair J, Kaslow R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, O'Brien SJ, Carrington M. Effect of a single amino acid change in MHC class I molecules on the rate of progres-sion to AIDS. N Engl J Med, 2001, 344(22): 1668-1675.
 Vallejo AN, Pease LR. Structure of the MHC A and B lo-cus promoters in hominoids. Insights on the evolution of the class I MHC multigene family. J Immunol, 1995, 154(8): 3912-3921.
 Xu Y, Hu Q, Liu Z, Shen Y, Liu X, Lin B, Wu Y, Chen S, Xu A. Sequence variations in the transcriptional regulatory region and intron1 of HLA-DQB1 gene and their linkage in southern Chinese ethnic groups. Immunogenetics, 2005, 57(7): 465-478.
 Yao Z, Volgger A, Scholz S, Albert E. Polymorphism of the HLA-C promotor region. Immunogenetics, 1997, 45(6): 428-431.
 Tan Z, Shon AM, Ober C. Evidence of balancing selection at the HLA-G promoter region. Hum Mol Genet, 2005, 14(23): 3619-3628.
 Griffioen M, Ouwerkerk IJ, Harten V, Schrier PI. HLA-B locus-specific downregulation in human melanoma re-quires enhancer A as well as a sequence element located downstream of the transcription initiation site. Immuno-genetics, 2000, 52(1-2): 121-128.
 Thomas R, Apps R, Qi Y, Gao X, Male V, O'hUigin C, O'Connor G, Ge D, Fellay J, Martin JN, Margolick J, Goedert JJ, Buchbinder S, Kirk GD, Martin MP, Telenti A, Deeks SG, Walker BD, Goldstein D, McVicar DW, Moffett A, Carrington M. HLA-C cell surface expression and con-trol of HIV/AIDS correlate with a variant upstream of HLA-C. Nat Genet, 2009, 41(12): 1290-1294.
 Delfino L, Morabito A, Ferrara GB. HLA-C sequence based typing: nucleotide analysis from exon 1 through exon 8. Identification of a new allele: Cw*0718. Tissue Antigens, 2003, 62(5): 418-425.
 Heinold A, Schaller-Suefling E, Opelz G, Scherer S, Tran TH. Identification of two novel HLA-alleles, HLA- A*02010103 and HLA-B*4455, and characterization of the complete genomic sequence of HLA-A*290201. Tissue Antigens, 2008, 72(4): 397-400.
 Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Hig-gins DG. The CLUSTAL_X windows interface: flexible strategies for multiple sequences alignment aided by quality analysis tools. Nucleic Acids Res, 1997, 25(24): 4876-4882.
 Rozas J, Sánchez-DelBarrio JC, Messeguer X, Rozas R. DNA polymorphism analyses by the coalescent and other methods. Bioinformatics, 2003, 19(18): 2496-2497.
 Kumar S, Tamura K, Nei M. MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform, 2004, 5(2): 150-163.
 Cox ST, McWhinnie AJ, Robinson J, Marsh SGE, Parham P, Madrigal JA, Little AM. Cloning and sequencing full-length HLA-B and -C genes. Tissue Antigens, 2003, 61(1): 20-48.
 Zhu F, He Y, Zhang W, He J, He J, Xu X, Yan L. Analysis of the complete genomic sequence of HLA-A alleles in the Chinese Han population. Int J Immunogenet, 2009, 36(6): 351-360.
 Van den Elsen PJ, Gobin SJ, Van Eggermond MC, Pei-jnenburg A. Regulation of MHC class I and II gene tran-scription: differences and similarities. Immunogenetics, 1998, 48(3): 208-221.
 Snyder SR, Waring JF, Zhu SZ, Kaplan S, Schultz J, Ginder GD. A 3'-transcribed region of the HLA-A2 gene mediates posttranscriptional stimulation by IFN-gamma. J Immunol, 2001, 166(6): 3966-3974.
 Decker CJ, Parker R. Diversity of cytoplasmic functions for the 3’untranslated region of eukaryotic transcripts. Curr Opin Cell Biol, 1995, 7(3): 386-392.
 盛熙晖, 杜立新. MicroRNA及其在人和动物上的研究进展. 遗传, 2007, 29(6): 651-658.
 孟详人, 郭军, 赵倩君, 马月辉, 关伟军, 刘娣, 狄冉, 乔海云, 那日苏. 11个绵羊品种MSTN基因非翻译区的变异. 遗传, 2008, 30(12): 1585-1590.
 Masuda K, Hiraki A, Fujii N, Watanabe T, Tanaka M, Matsue K, Ogama Y, Ouchida M, Shimizu K, Ikeda K, Tanimoto M. Loss or down-regulation of HLA class I ex-pression at the allelic level in freshly isolated leukemic blasts. Cancer Sci, 2007, 98(1): 102-108.
 Liu H, Fu J, Bouvier M. Allele- and locus-specific recog-nition of class I MHC molecules by the immunomodula-tory E3-19K protein from adenovirus. J Immunol, 2007, 178(7): 4567-4575.