Minimal Haplotype Tagging

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 17; pp. 9900 - 9905
• Main Authors: Sebastiani, Paola, Lazarus, Ross, Weiss, Scott T., Kunkel, Louis M., Kohane, Isaac S., Ramoni, Marco F.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 19-08-2003; National Acad Sciences
• Subjects: African Americans; Algorithms; Alleles; Biological Sciences; Black or African American; Black People - genetics; Disease; Evolution, Molecular; Female; Genetic Variation; Genetics; Genomes; Genomics; Haplotypes; Haplotypes - genetics; Human genetics; Humans; Male; Mathematical functions; Medical genetics; Medical schools; Models, Genetic; Polymorphism; Polymorphism, Single Nucleotide; Proportions; White People - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1633613100

The high frequency of single-nucleotide polymorphisms (SNPs) in the human genome presents an unparalleled opportunity to track down the genetic basis of common diseases. At the same time, the sheer number of SNPs also makes unfeasible genomewide disease association studies. The haplotypic nature of the human genome, however, lends itself to the selection of a parsimonious set of SNPs, called haplotype tagging SNPs (htSNPs), able to distinguish the haplotypic variations in a population. Current approaches rely on statistical analysis of transmission rates to identify htSNPs. In contrast to these approximate methods, this contribution describes an exact, analytical, and lossless method, called BEST (Best Enumeration of SNP Tags), able to identify the minimum set of SNPs tagging an arbitrary set of haplotypes from either pedigree or independent samples. Our results confirm that a small proportion of SNPs is sufficient to capture the haplotypic variations in a population and that this proportion decreases exponentially as the haplotype length increases. We used BEST to tag the haplotypes of 105 genes in an African-American and a European-American sample. An interesting finding of this analysis is that the vast majority (95%) of the htSNPs in the European-American sample is a subset of the htSNPs of the African-American sample. This result seems to provide further evidence that a severe bottleneck occurred during the founding of Europe and the conjectured "Out of Africa" event.