title: Identification of the third/extra allele for forensic application in cases with TPOX tri-allelic pattern.
abstract: Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications.
authors.affiliation: PUCRS, Faculdade de Biociências, Laboratório de Genética Humana e Molecular, Av. Ipiranga, 6681, P12C, sala 233, Porto Alegre, RS 90619-900, Brazil.
authors.forename: Juliane Bentes
authors.initials: JB
authors.lastname: Picanço
authors.affiliation: PUCRS, Faculdade de Biociências, Laboratório de Genética Humana e Molecular, Av. Ipiranga, 6681, P12C, sala 233, Porto Alegre, RS 90619-900, Brazil.
authors.forename: Paulo Eduardo
authors.initials: PE
authors.lastname: Raimann
authors.affiliation: Instituto de Medicina Social e de Criminologia de São Paulo - IMESC, Rua Barra Funda, 824, São Paulo, SP 01152-000, Brazil.
authors.forename: Carlos Henrique Ares Silveira da
authors.initials: CHASD
authors.lastname: Motta
authors.affiliation: PUCRS, Faculdade de Biociências, Laboratório de Genética Humana e Molecular, Av. Ipiranga, 6681, P12C, sala 233, Porto Alegre, RS 90619-900, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Rodenbusch
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology, Universidade do Porto, Porto, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Gusmão
authors.affiliation: PUCRS, Faculdade de Biociências, Laboratório de Genética Humana e Molecular, Av. Ipiranga, 6681, P12C, sala 233, Porto Alegre, RS 90619-900, Brazil. Electronic address: csalho@pucrs.br.
authors.forename: Clarice Sampaio
authors.initials: CS
authors.lastname: Alho
mesh_terms: D000328:Adult; D000483:Alleles; D001938:Brazil; D002648:Child; D041321:Chromosomes, Human, X; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D053803:Forensic Genetics / Q000379:methods*; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats
chemical_list: D004247:DNA
keywords: Extra allele; TPOX STR profile; Tri-allelic pattern