2007
DOI: 10.1111/j.2007.0018-0661.01994.x
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Haplotype inference from diploid sequence data: evaluating performance using non-neutral MHC sequences

Abstract: The direct sequencing of PCR products from diploid organisms is problematic because of ambiguities associated with phase inference in multi-site heterozygotes. Several molecular methods such as cloning, SSCP, and DGGE have been developed to empirically reduce diploid sequences to their constitutive haploid components, but in theory these empirical approaches can be supplanted by analytical treatment of diploid sequences. Analytical approaches are more desirable than molecular methods because of the added time … Show more

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Cited by 26 publications
(37 citation statements)
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“…We then used PHASE (Stephens et al 2001) to determine phase-ordered genotypes analytically. As a quality control measure, some individuals from 2002 and 2003 were also directly sequenced and analyzed with PHASE, then confirmed with the cloning data (Bos et al 2007). Any individuals that contained unique alleles were subsequently cloned and sequenced as described earlier.…”
Section: Major Histocompatibility Genotypingmentioning
confidence: 99%
See 1 more Smart Citation
“…We then used PHASE (Stephens et al 2001) to determine phase-ordered genotypes analytically. As a quality control measure, some individuals from 2002 and 2003 were also directly sequenced and analyzed with PHASE, then confirmed with the cloning data (Bos et al 2007). Any individuals that contained unique alleles were subsequently cloned and sequenced as described earlier.…”
Section: Major Histocompatibility Genotypingmentioning
confidence: 99%
“…An additional 47 individuals were genotyped analytically via direct sequencing of PCR products followed by PHASE analysis (Stephens et al 2001;Bos et al 2007). The MH amplicon consisted of 254 nucleotides, 41 (16%) of which were variable.…”
Section: Major Histocompatibilitymentioning
confidence: 99%
“…The present work, together with two recent papers [23,24], extends these assessments to non-coding anonymous or intronic nDNA from other organisms. The consistently good performance suggests that PHASE is robust to some violations of the underlying neutral coalescent model (e.g., selection, kin clustering, population structure [53]).…”
Section: Discussionmentioning
confidence: 99%
“…Indeed, Bos et al . 's [53] recommendation for ground-truthing a sub-sample of the haplotypes inferred by PHASE is well justified.…”
Section: Discussionmentioning
confidence: 99%
“…PHASE uses a Bayesian algorithm to infer haplotypes from diploid genotypic data while incorporating recombination and the decay of linkage disequilibrium (LD) with genetic distance, and it is as effective or better than cloning for resolving highly polymorphic sequences [44], [45]. We first analyzed each composite sequence, the consensus of both alleles, using the default software settings (100 main iterations, 1 thinning interval, 100 burn-in) followed by 1,000 main iterations and 1,000 burn-in (-X10 option) for the final iteration.…”
Section: Methodsmentioning
confidence: 99%