Evaluation of two methods for computational HLA haplotypes inference using a real dataset

Bettencourt, Bruno Filipe; Santos, Margarida Rodrigues; Fialho, Raquel Nunes; Couto, Ana Rita; Peixoto, Maria Manuela; Pinheiro, João Paulo; Spínola, Hélder; Mora, Marian Gantes; Santos, Cristina; Brehm, António; Bruges-Armas, Jácome

doi:10.1186/1471-2105-9-68

Cited by 13 publications

(12 citation statements)

References 25 publications

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“…It should be noted that the presence of B8 and DR3, DQ2 is not absolutely indicative of a complete haplotype since recombined alleles may be inherited from each parent. We tested this by imputing haplotypes using PHASE 2.1.1, which has shown to have superior HLA haplotype reconstruction than the Expectation-Maximization algorithm (Bettencourt et al 2008);(Castelli et al 2010). The frequency of imputed B8, DR3, DQ2 haplotypes was 14.1% in MG, 24.7% in EOMG, 25.3% in IgAD, and 9.7% in a control population (n=672) previously typed (Ferreira et al n.d.).…”

Section: Resultsmentioning

confidence: 99%

Concomitant autoimmunity in myasthenia gravis — Lack of association with IgA deficiency

Ramanujam

Piehl

Pirskanen

et al. 2011

Journal of Neuroimmunology

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A marked increase in concomitant autoimmune diseases has previously been noted in patients with myasthenia gravis (MG). We show that these diseases occur both before and after the onset of MG and that the process is not influenced by thymectomy. IgA deficiency (IgAD), which is strongly associated with the same HLA haplotype as early onset MG, has recently been suggested to be an autoimmune disease. However, there was no increase in the prevalence of IgAD in a large cohort of Swedish MG patients.

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Section: Resultsmentioning

confidence: 99%

Concomitant autoimmunity in myasthenia gravis — Lack of association with IgA deficiency

Ramanujam

Piehl

Pirskanen

et al. 2011

Journal of Neuroimmunology

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“…The Markov chain approximation was used with 100000 steps and 1000 dememorization steps definition. The distribution of HLA-DQ-DR haplotypes was analyzed in all patients and controls, using pseudo-Bayesian based ELB approach [17]. The software Arlequin 3.1 was run by using the following settings: ε = 1e−7; 5 significant digits for output 50 starting points for ELB algorithm and a maximum of 1000 iterations.…”

Section: Methodsmentioning

confidence: 99%

HLA-DRB1 Shared Epitope-Dependent DR-DQ Haplotypes Are Associated with Both Anti-CCP–Positive and –Negative Rheumatoid Arthritis in Chinese Han

et al. 2013

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The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant RA association (P = 1.35×10−6). The grouped DRB1 SE alleles showed great association with RA (P = 3.88×10−13). The DRB1 DRRAA alleles displayed significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71×10−13) and -negative RA (P = 3.89×10−5). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA.

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“…Accuracy was measured by the mean squared error (MSE). The MSE reflects the overall difference in haplotype frequencies between the estimated and true frequency values: , where h is the total number of haplotypes considering the real and estimated haplotypes, and P est and P real are the estimated and real haplotype frequencies for haplotype k (22).…”

Section: Samples and Methodsmentioning

confidence: 99%

“…Taking into account the high number of alleles at each HLA locus, the number of haplotypes observed in several populations is smaller than the expected one under the hypothesis of absence of LD, indicating that some HLA alleles probably segregate as a single genetic block. In a recent study, Bettencourt and colleagues have addressed this issue in a dataset of Portuguese individuals (22), who are supposed to be more homogeneous than Brazilians (23). Because Brazilians represent one of the most heterogeneous populations in the world as the result of five centuries of interethnic crosses of people from three continents (European colonizers mainly represented by the Portuguese, the African slaves and the autochthonous Amerindians (24)), one may expect an excess of low‐frequency alleles across the genome (25), which would yield a larger number of possible haplotypes.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of computational methods for the reconstruction of HLA haplotypes

et al. 2010

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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.

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Evaluation of two methods for computational HLA haplotypes inference using a real dataset

Cited by 13 publications

References 25 publications

Concomitant autoimmunity in myasthenia gravis — Lack of association with IgA deficiency

Concomitant autoimmunity in myasthenia gravis — Lack of association with IgA deficiency

HLA-DRB1 Shared Epitope-Dependent DR-DQ Haplotypes Are Associated with Both Anti-CCP–Positive and –Negative Rheumatoid Arthritis in Chinese Han

Evaluation of computational methods for the reconstruction of HLA haplotypes

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