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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Evaluation of computational methods for the reconstruction of HLA haplotypes

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Autor(es):
Castelli, E. C. [1] ; Mendes-Junior, C. T. [2] ; Veiga-Castelli, L. C. [3] ; Pereira, N. F. [4] ; Petzl-Erler, M. L. [5] ; Donadi, E. A. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, BR-14049900 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, BR-14049900 Ribeirao Preto, SP - Brazil
[4] Univ Fed Parana, Hosp Clin, Immunogenet Lab, BR-80060000 Curitiba, Parana - Brazil
[5] Univ Fed Parana, Dept Genet, Lab Genet Mol Humana, BR-80060000 Curitiba, Parana - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: TISSUE ANTIGENS; v. 76, n. 6, p. 459-466, DEC 2010.
Citações Web of Science: 17
Resumo

Human leukocyte antigen (HLA) haplotypes are frequently evaluated for population history inferences and association studies. However, the available typing techniques for the main HLA loci usually do not allow the determination of the allele phase and the constitution of a haplotype, which may be obtained by a very time-consuming and expensive family-based segregation study. Without the family-based study, computational inference by probabilistic models is necessary to obtain haplotypes. Several authors have used the expectation-maximization (EM) algorithm to determine HLA haplotypes, but high levels of erroneous inferences are expected because of the genetic distance among the main HLA loci and the presence of several recombination hotspots. In order to evaluate the efficiency of computational inference methods, 763 unrelated individuals stratified into three different datasets had their haplotypes manually defined in a family-based study of HLA-A, -B, -DRB1 and -DQB1 segregation, and these haplotypes were compared with the data obtained by the following three methods: the Expectation-Maximization (EM) and Excoffier-Laval-Balding (ELB) algorithms using the arlequin 3.11 software, and the PHASE method. When comparing the methods, we observed that all algorithms showed a poor performance for haplotype reconstruction with distant loci, estimating incorrect haplotypes for 38%-57% of the samples considering all algorithms and datasets. We suggest that computational haplotype inferences involving low-resolution HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 haplotypes should be considered with caution. (AU)

Processo FAPESP: 07/58420-4 - Polimorfismos da região promotora e expressão de HLA-G em pacientes com histórico de carcinoma de células transicionais da bexiga urinária
Beneficiário:Erick da Cruz Castelli
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado