Improving global and regional resolution of male lineage differentiation by simple single-copy Y-chromosomal short tandem repeat polymorphisms

Abstract

We analyzed 67 short tandem repeat polymorphisms from the non-recombining part of the Y-chromosome (Y-STRs), including 49 rarely studied simple single-copy (ss)Y-STRs and 18 widely used Y-STRs, in 590 males from 51 populations belonging to 8 worldwide regions (HGDP-CEPH panel). Although autosomal DNA profiling provided no evidence for close relationship, we found 18 Y-STR haplotypes (defined by 67 Y-STRs) that were shared by two to five men in 13 worldwide populations, revealing high and widespread levels of cryptic male relatedness. Maximal (95.9%) haplotype resolution was achieved with the best 25 out of 67 Y-STRs in the global dataset, and with the best 3-16 markers in regional datasets (89.6-100% resolution). From the 49 rarely studied ssY-STRs, the 25 most informative markers were sufficient to reach the highest possible male lineage differentiation in the global (92.2% resolution), and 3-15 markers in the regional datasets (85.4-100%). Considerably lower haplotype resolutions were obtained with the three commonly used Y-STR sets (Minimal Haplotype, PowerPlex Y, and AmpFlSTR Yfiler. Six ssY-STRs (DYS481, DYS533, DYS549, DYS570, DYS576 and DYS643) were most informative to supplement the existing Y-STR kits for increasing haplotype resolution, or - together with additional ssY-STRs - as a new set for maximizing male lineage differentiation. Mutation rates of the 49 ssY-STRs were estimated from 403 meiotic transfers in deep-rooted pedigrees, and ranged from approximately 4.8 x 10(-4) for 31 ssY-STRs with no mutations observed to 1.3 x 10(-2) and 1.5 x 10(-2) for DYS570 and DYS576, respectively, the latter representing the highest mutation rates reported for human Y-STRs so far. Our findings thus demonstrate that ssY-STRs are useful for maximizing global and regional resolution of male lineages, either as a new set, or when added to commonly used Y-STR sets, and support their application to forensic, genealogical and anthropological studies.

Figure 1

Maximal Y-STR haplotype resolution in global and regional analyses using males from the H952 set of the worldwide HGDP-CEPH samples considering i) 67 Y-STRs, ii) 49 simple single copy Y-STRs, iii) 17 Y-STRs included in the AmpFlSTR® Yfiler® PCR Amplification Kit (Applied Biosystems), iv) 12 Y-STRs included in the PowerPlex Y® System (Promega), and v) 9 Y-STRs comprising the Minimal Haplotype.

Figure 2

Minimal number of markers needed to reach the maximum Y-STR haplotype resolution in global and regional analyses using males from the H952 set of the worldwide HGDP-CEPH samples considering i) 67 Y-STRs, ii) 49 simple single copy Y-STRs, iii) 17 Y-STRs included in the AmpFlSTR® Yfiler® PCR Amplification Kit (Applied Biosystems), iv) 12 Y-STRs included in the PowerPlex Y® System (Promega), and v) 9 Y-STRs comprising the Minimal Haplotype.

Figure 3

Loss of haplotype resolution in global and regional analyses using males from the H952 set of the worldwide HGDP-CEPH samples in relation to the maximal haplotype resolution from analyzing 67 Y-STRs considering i) 49 simple single copy Y-STRs, ii) 17 Y-STRs included in the AmpFlSTR® Yfiler® PCR Amplification Kit (Applied Biosystems), iii) 12 Y-STRs included in the PowerPlex Y® System (Promega), and iv) 9 Y-STRs comprising the Minimal Haplotype.

Figure 4

Gain of haplotype resolution obtained with simple single copy Y-STRs when supplementing commonly-used Y-STR sets in global and regional analyses using males from the H952 set of the worldwide HGDP-CEPH samples relative to the resolution provided by the initial analysis of commonly-used Y-STR sets: i) 17 Y-STRs included in the AmpFlSTR® Yfiler® PCR Amplification Kit (Applied Biosystems), ii) 12 Y-STRs included in the PowerPlex Y® System (Promega), and iii) 9 Y-STRs comprising the Minimal Haplotype.

Figure 5

Minimal number of simple single copy Y-STRs needed to reach the maximum haplotype resolution when supplementing commonly-used Y-STR sets in global and regional analyses using males from the H952 set of the worldwide HGDP-CEPH samples: i) 17 Y-STRs included in the AmpFlSTR® Yfiler® PCR Amplification Kit (Applied Biosystems), ii) 12 Y-STRs included in the PowerPlex Y® System (Promega), and iii) 9 Y-STRs comprising the Minimal Haplotype.