Analysis of full intronic sequences of HLA-A alleles / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
; (6): 638-643, 2011.
Article
en Zh
| WPRIM
| ID: wpr-295564
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the full intronic sequences of human leukocyte antigen (HLA)-A alleles in Han Chinese.</p><p><b>METHODS</b>The full-length HLA-A alleles, including 8 exons and 7 introns, were amplified with a long-template PCR system from 165 donors from the Chinese Marrow Donor Program (CMDP). The products were cloned into a PGEM-T Vector System and sequenced from both directions. Genetic analysis was performed using a MEGA4.0 software. All sequences were aligned with a ClustalW algorithm. Phylogenetic trees were constructed with a neighbor-joining method. Genetic distances were estimated based on p-distance, and a bootstrap analysis was applied for assessing the confidence limits of the trees.</p><p><b>RESULTS</b>A total of thirty-three full-length sequences of HLA-A alleles, containing 2902-2918 nucleotides, were derived. A total of 138 point mutations and 9 insertions or deletions were found among the 7 introns, which showed remarkable group specificity. Intron 1 appeared to be most polymorphic with the highest average GC content and evolutionary distances. Eight phylogenetic trees were constructed respectively with the derived full-length sequences as well as each of the 7 introns sequences. Based on full-length sequences, sequences of the HLA-A locus were classified into five groups: group I consisted of A*01/03/11/30; group II consisted of A*23/24(A9); group III consisted of A*02/68/69(A2/28); group IV consisted of A*26/34(A10); and group V consisted of A*29/31/32/33/74(A19). The five groups were derived from two ancient lineages, one including groups I and II, and another including groups III, IV and V. No substantial difference was detected between the trees constructed with the 7 intronic sequences, except that group II belonged to different lineages based on introns 2-5 and introns 1 and 7. The A*30 variant cluster was close to group I (A*01/03/11/30) and differed from group V (A19).</p><p><b>CONCLUSION</b>The full-length sequences of 18 alleles have been submitted to GenBank and accepted by the international ImMunoGeneTics database (IMGT). Polymorphisms identified within the introns of HLA-A alleles showed remarkable group specificity. Such sequences seem to have substantially contributed to the recombination of the HLA-A alleles. The A*30 may represent an atypical group in which the rates of gene conversion and mutation have been unusually high.</p>
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Filogenia
/
Datos de Secuencia Molecular
/
Intrones
/
Antígenos HLA-A
/
Análisis de Secuencia de ADN
/
Polimorfismo de Nucleótido Simple
/
Alelos
/
Genética
Límite:
Humans
Idioma:
Zh
Revista:
Chinese Journal of Medical Genetics
Año:
2011
Tipo del documento:
Article