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A phylogenetic framework facilitates Y-STR variant discovery and classification via massively parallel sequencing.
Forensic Sci Int Genet. 2018 07; 35:97-106.FS

Abstract

Short tandem repeats on the male-specific region of the Y chromosome (Y-STRs) are permanently linked as haplotypes, and therefore Y-STR sequence diversity can be considered within the robust framework of a phylogeny of haplogroups defined by single nucleotide polymorphisms (SNPs). Here we use massively parallel sequencing (MPS) to analyse the 23 Y-STRs in Promega's prototype PowerSeq™ Auto/Mito/Y System kit (containing the markers of the PowerPlex® Y23 [PPY23] System) in a set of 100 diverse Y chromosomes whose phylogenetic relationships are known from previous megabase-scale resequencing. Including allele duplications and alleles resulting from likely somatic mutation, we characterised 2311 alleles, demonstrating 99.83% concordance with capillary electrophoresis (CE) data on the same sample set. The set contains 267 distinct sequence-based alleles (an increase of 58% compared to the 169 detectable by CE), including 60 novel Y-STR variants phased with their flanking sequences which have not been reported previously to our knowledge. Variation includes 46 distinct alleles containing non-reference variants of SNPs/indels in both repeat and flanking regions, and 145 distinct alleles containing repeat pattern variants (RPV). For DYS385a,b, DYS481 and DYS390 we observed repeat count variation in short flanking segments previously considered invariable, and suggest new MPS-based structural designations based on these. We considered the observed variation in the context of the Y phylogeny: several specific haplogroup associations were observed for SNPs and indels, reflecting the low mutation rates of such variant types; however, RPVs showed less phylogenetic coherence and more recurrence, reflecting their relatively high mutation rates. In conclusion, our study reveals considerable additional diversity at the Y-STRs of the PPY23 set via MPS analysis, demonstrates high concordance with CE data, facilitates nomenclature standardisation, and places Y-STR sequence variants in their phylogenetic context.

Authors+Show Affiliations

Department of Genetics & Genome Biology, University of Leicester, University Road, Leicester LE1 7RH, UK.Department of Genetics & Genome Biology, University of Leicester, University Road, Leicester LE1 7RH, UK. Electronic address: maj4@le.ac.uk.Department of Genetics & Genome Biology, University of Leicester, University Road, Leicester LE1 7RH, UK. Electronic address: jw418@le.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29679929

Citation

Huszar, Tunde I., et al. "A Phylogenetic Framework Facilitates Y-STR Variant Discovery and Classification Via Massively Parallel Sequencing." Forensic Science International. Genetics, vol. 35, 2018, pp. 97-106.
Huszar TI, Jobling MA, Wetton JH. A phylogenetic framework facilitates Y-STR variant discovery and classification via massively parallel sequencing. Forensic Sci Int Genet. 2018;35:97-106.
Huszar, T. I., Jobling, M. A., & Wetton, J. H. (2018). A phylogenetic framework facilitates Y-STR variant discovery and classification via massively parallel sequencing. Forensic Science International. Genetics, 35, 97-106. https://doi.org/10.1016/j.fsigen.2018.03.012
Huszar TI, Jobling MA, Wetton JH. A Phylogenetic Framework Facilitates Y-STR Variant Discovery and Classification Via Massively Parallel Sequencing. Forensic Sci Int Genet. 2018;35:97-106. PubMed PMID: 29679929.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A phylogenetic framework facilitates Y-STR variant discovery and classification via massively parallel sequencing. AU - Huszar,Tunde I, AU - Jobling,Mark A, AU - Wetton,Jon H, Y1 - 2018/04/12/ PY - 2018/01/19/received PY - 2018/03/14/revised PY - 2018/03/28/accepted PY - 2018/4/22/pubmed PY - 2018/12/12/medline PY - 2018/4/22/entrez KW - Massively parallel sequencing KW - PPY23 KW - PowerSeq system KW - Repeat pattern variation (RPV) KW - Single nucleotide polymorphism (SNP) KW - Y-STRs SP - 97 EP - 106 JF - Forensic science international. Genetics JO - Forensic Sci Int Genet VL - 35 N2 - Short tandem repeats on the male-specific region of the Y chromosome (Y-STRs) are permanently linked as haplotypes, and therefore Y-STR sequence diversity can be considered within the robust framework of a phylogeny of haplogroups defined by single nucleotide polymorphisms (SNPs). Here we use massively parallel sequencing (MPS) to analyse the 23 Y-STRs in Promega's prototype PowerSeq™ Auto/Mito/Y System kit (containing the markers of the PowerPlex® Y23 [PPY23] System) in a set of 100 diverse Y chromosomes whose phylogenetic relationships are known from previous megabase-scale resequencing. Including allele duplications and alleles resulting from likely somatic mutation, we characterised 2311 alleles, demonstrating 99.83% concordance with capillary electrophoresis (CE) data on the same sample set. The set contains 267 distinct sequence-based alleles (an increase of 58% compared to the 169 detectable by CE), including 60 novel Y-STR variants phased with their flanking sequences which have not been reported previously to our knowledge. Variation includes 46 distinct alleles containing non-reference variants of SNPs/indels in both repeat and flanking regions, and 145 distinct alleles containing repeat pattern variants (RPV). For DYS385a,b, DYS481 and DYS390 we observed repeat count variation in short flanking segments previously considered invariable, and suggest new MPS-based structural designations based on these. We considered the observed variation in the context of the Y phylogeny: several specific haplogroup associations were observed for SNPs and indels, reflecting the low mutation rates of such variant types; however, RPVs showed less phylogenetic coherence and more recurrence, reflecting their relatively high mutation rates. In conclusion, our study reveals considerable additional diversity at the Y-STRs of the PPY23 set via MPS analysis, demonstrates high concordance with CE data, facilitates nomenclature standardisation, and places Y-STR sequence variants in their phylogenetic context. SN - 1878-0326 UR - https://www.unboundmedicine.com/medline/citation/29679929/A_phylogenetic_framework_facilitates_Y_STR_variant_discovery_and_classification_via_massively_parallel_sequencing_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1872-4973(18)30027-9 DB - PRIME DP - Unbound Medicine ER -