Haplotype block: a new type of forensic DNA markers

Abstract

Forensic DNA analysis is currently performed using highly discriminating short tandem repeat (STR) markers. SNPs are being investigated as adjunct tools for human identity testing because of their abundance in the human genome, utility for genotyping degraded DNA samples, and amenability to automation. While SNPs can provide an alternative approach, on a per locus basis they have a lower power of discrimination (PD) than STRs. With the discovery of block structures in the human genome, a novel set of SNP markers are available for further exploration of forensic utility. Several neighboring, tightly linked SNPs are inherited together and form a haplotype block, which as a haploblock has a higher discrimination power than the individual SNPs within the block. Candidate haplotype blocks were selected from three major populations (Caucasian, East Asian, and African) using the following parameters: maximum match probability reduction = 0.85, linkage disequilibrium (LD) r(2) ≥ 0.7, maximum F(st) = 0.06, minimum number of SNPs = 3, minimum heterozygosity = 0.2, and minimum number of haplotypes = 3. From the HapMap Phase II data, 253 haploblocks were identified on the 22 autosomal chromosomes. After removing haploblocks deviating from the Hardy-Weinberg equilibrium (HWE) or in LD with other haploblocks, 24 haploblocks remained as candidates for forensic consideration. The cumulative PD of these blocks can reach 10(-12) in the populations studied. The data support within and between haplotype independence even when they are syntenic. We propose guidelines for evidence interpretation that address the application of haplotype blocks for transfer evidence, mixture, and kinship analyses.

Mini-haplotypes as lineage informative SNPs and ancestry inference SNPs

“…If both r 2 and D' equal 1.0 then only two combinations occur and one of the two SNPs is completely redundant (that is, uninformative). This is apparently the case for the 'haploblocks' identified by Ge et al 3 As seen in Figure 1, and our studies of various genes cited earlier, some requisite recombination events appear to have occurred and the resulting haplotype became common early in human dispersal. These recombinant haplotypes may have persisted as identical by descent (IBD) lineages since their origin.…”

“…We defined and have advocated developing such multi-SNP haplotype systems as one type of forensic DNA marker, lineage informative SNPs, LISNPs (Pakstis et al, 1 Butler et al; 2 see also Ge et al 3 ). The multiple alleles (haplotypes) available in these more complex systems can serve to identify relatives with higher probabilities than simple di-allelic SNPs.…”

“…Based on our interest in haplotypes and their global patterns, we have recently begun pursuing the same objective of finding forensically useful haplotype systems for familial identification as they can have high heterozygosity, the relevant issue for familial identification. Our strategy is very different from that of Ge et al 3 We focus on finding very closely spaced SNPs in a region that is not a 'hot spot' for recombination but also does not show strong linkage disequilibrium (LD). Our criteria are to find regions in which we can (1) clearly see multiple haplotypes that show conservation of evolutionary lineages that have evolved from the ancestral human haplotype and (2) show no evidence of recurring recombination (though there may be some historic recombinants that have drifted to sufficiently high frequency to become common haplotypes).…”

“…Our criteria are to find regions in which we can (1) clearly see multiple haplotypes that show conservation of evolutionary lineages that have evolved from the ancestral human haplotype and (2) show no evidence of recurring recombination (though there may be some historic recombinants that have drifted to sufficiently high frequency to become common haplotypes). Such regions are not necessarily 'LD blocks' or 'haploblocks' , as those terms are usually used 3,4 and are not necessarily in strong LD. This approach of haplotype lineage identification is justified by and illustrated in our recent work on other projects in which we have identified the gene segments with multiple haplotypes (alleles) but that show no evidence of historic recombination or at most a single historic recombinant: ADH7; 5 POLB; 6 SLITRK1; 7 CYP2E1; 8 CYP2C8; 9 ADH1B; 10 OCA2 11 and TAS2R16.…”

Genesis of ancestral haplotypes: RNA modifications and reverse transcription–mediated polymorphisms

“…In our opinion the full implication of this genomic picture are still not fully appreciated by many biomedical scientists despite the common place application of block concepts to GWA analyses for disease or complex trait discovery [18][19][20], to forensics [21,22] and the recognition that the synteny of the haplotype block structure is conserved across mammals [5,23].…”