title: Robustness of inference of haplotype block structure.
abstract: In this report, we examine the validity of the haplotype block concept by comparing block decompositions derived from public data sets by variants of several leading methods of block detection. We first develop a statistical method for assessing the concordance of two block decompositions. We then assess the robustness of inferred haplotype blocks to the specific detection method chosen, to arbitrary choices made in the block-detection algorithms, and to the sample analyzed. Although the block decompositions show levels of concordance that are very unlikely by chance, the absolute magnitude of the concordance may be low enough to limit the utility of the inference. For purposes of SNP selection, it seems likely that methods that do not arbitrarily impose block boundaries among correlated SNPs might perform better than block-based methods.
authors.affiliation: Celera Genomics Research, Rockville, MD 20850, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Schwartz
authors.forename: Bjarni V
authors.initials: BV
authors.lastname: Halldórsson
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
authors.forename: Sorin
authors.initials: S
authors.lastname: Istrail
mesh_terms: D000465:Algorithms; D030541:Databases, Genetic; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*