Publications by authors named "Martín R Whittle"

9 Publications

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Noninvasive prenatal paternity determination using microhaplotypes: a pilot study.

BMC Med Genomics 2020 10 23;13(1):157. Epub 2020 Oct 23.

Department of Clinical Toxicological Analyzes, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

Background: The use of noninvasive techniques to determine paternity prenatally is increasing because it reduces the risks associated with invasive procedures. Current methods, based on SNPs, use the analysis of at least 148 markers, on average.

Methods: To reduce the number of regions, we used microhaplotypes, which are chromosomal segments smaller than 200 bp containing two or more SNPs. Our method employs massively parallel sequencing and analysis of microhaplotypes as genetic markers. We tested 20 microhaplotypes and ascertained that 19 obey Hardy-Weinberg equilibrium and are independent, and data from the 1000 Genomes Project were used for population frequency and simulations.

Results: We performed simulations of true and false paternity, using the 1000 Genomes Project data, to confirm if the microhaplotypes could be used as genetic markers. We observed that at least 13 microhaplotypes should be used to decrease the chances of false positives. Then, we applied the method in 31 trios, and it was able to correctly assign the fatherhood in cases where the alleged father was the real father, excluding the inconclusive results. We also cross evaluated the mother-plasma duos with the alleged fathers for false inclusions within our data, and we observed that the use of at least 15 microhaplotypes in real data also decreases the false inclusions.

Conclusions: In this work, we demonstrated that microhaplotypes can be used to determine prenatal paternity by using only 15 regions and with admixtures of DNA.
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http://dx.doi.org/10.1186/s12920-020-00806-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584091PMC
October 2020

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.

Authors:
Josephine Purps Sabine Siegert Sascha Willuweit Marion Nagy Cíntia Alves Renato Salazar Sheila M T Angustia Lorna H Santos Katja Anslinger Birgit Bayer Qasim Ayub Wei Wei Yali Xue Chris Tyler-Smith Miriam Baeta Bafalluy Begoña Martínez-Jarreta Balazs Egyed Beate Balitzki Sibylle Tschumi David Ballard Denise Syndercombe Court Xinia Barrantes Gerhard Bäßler Tina Wiest Burkhard Berger Harald Niederstätter Walther Parson Carey Davis Bruce Budowle Helen Burri Urs Borer Christoph Koller Elizeu F Carvalho Patricia M Domingues Wafaa Takash Chamoun Michael D Coble Carolyn R Hill Daniel Corach Mariela Caputo Maria E D'Amato Sean Davison Ronny Decorte Maarten H D Larmuseau Claudio Ottoni Olga Rickards Di Lu Chengtao Jiang Tadeusz Dobosz Anna Jonkisz William E Frank Ivana Furac Christian Gehrig Vincent Castella Branka Grskovic Cordula Haas Jana Wobst Gavrilo Hadzic Katja Drobnic Katsuya Honda Yiping Hou Di Zhou Yan Li Shengping Hu Shenglan Chen Uta-Dorothee Immel Rüdiger Lessig Zlatko Jakovski Tanja Ilievska Anja E Klann Cristina Cano García Peter de Knijff Thirsa Kraaijenbrink Aikaterini Kondili Penelope Miniati Maria Vouropoulou Lejla Kovacevic Damir Marjanovic Iris Lindner Issam Mansour Mouayyad Al-Azem Ansar El Andari Miguel Marino Sandra Furfuro Laura Locarno Pablo Martín Gracia M Luque Antonio Alonso Luís Souto Miranda Helena Moreira Natsuko Mizuno Yasuki Iwashima Rodrigo S Moura Neto Tatiana L S Nogueira Rosane Silva Marina Nastainczyk-Wulf Jeanett Edelmann Michael Kohl Shengjie Nie Xianping Wang Baowen Cheng Carolina Núñez Marian Martínez de Pancorbo Jill K Olofsson Niels Morling Valerio Onofri Adriano Tagliabracci Horolma Pamjav Antonia Volgyi Gusztav Barany Ryszard Pawlowski Agnieszka Maciejewska Susi Pelotti Witold Pepinski Monica Abreu-Glowacka Christopher Phillips Jorge Cárdenas Danel Rey-Gonzalez Antonio Salas Francesca Brisighelli Cristian Capelli Ulises Toscanini Andrea Piccinini Marilidia Piglionica Stefania L Baldassarra Rafal Ploski Magdalena Konarzewska Emila Jastrzebska Carlo Robino Antti Sajantila Jukka U Palo Evelyn Guevara Jazelyn Salvador Maria Corazon De Ungria Jae Joseph Russell Rodriguez Ulrike Schmidt Nicola Schlauderer Pekka Saukko Peter M Schneider Miriam Sirker Kyoung-Jin Shin Yu Na Oh Iulia Skitsa Alexandra Ampati Tobi-Gail Smith Lina Solis de Calvit Vlastimil Stenzl Thomas Capal Andreas Tillmar Helena Nilsson Stefania Turrina Domenico De Leo Andrea Verzeletti Venusia Cortellini Jon H Wetton Gareth M Gwynne Mark A Jobling Martin R Whittle Denilce R Sumita Paulina Wolańska-Nowak Rita Y Y Yong Michael Krawczak Michael Nothnagel Lutz Roewer

Forensic Sci Int Genet 2014 Sep 28;12:12-23. Epub 2014 Apr 28.

Department of Forensic Genetics, Institute of Legal Medicine and Forensic Sciences, Charité-Universitätsmedizin, Berlin, Germany. Electronic address:

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.
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http://dx.doi.org/10.1016/j.fsigen.2014.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127773PMC
September 2014

Comparison of southern Chinese Han and Brazilian Caucasian mutation rates at autosomal short tandem repeat loci used in human forensic genetics.

Int J Legal Med 2014 Jan 3;128(1):1-9. Epub 2013 Apr 3.

Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of Justice, Shanghai, People's Republic of China.

The short tandem repeat (STR) loci used in human genetic studies are characterized by having relatively high mutation rates. In particular, to ensure an appropriate evaluation of genetic evidence in parentage and forensic analyses, it is essential to have accurate estimates of the mutation rates associated with the commonly used autosomal and sex chromosome STR loci. Differences in STR mutation rates between different ethnic groups should also be determined. Mutation data from two laboratories working with different ethnic groups were extracted from many meiotic transmissions ascertained for 15 autosomal STR loci currently used in forensic routine. Forty-five thousand and eighty-five trios were checked for the biological consistency of maternity and paternity through the analysis of a minimum of 15 loci. Mutations were scored as paternal, maternal, or ambiguous according to the most parsimonious explanation for the inconsistency, using always the least requiring hypothesis in terms of number of repeat differences. The main findings are: (a) the overall mutation rate across the 15 loci was 9.78 × 10(-4) per gamete per generation (95% CI = 9.30 × 10(-4)-1.03 × 10(-3)), and with just 48 (out of 1,587) exceptions, all of the mutations were single-step; (b) repeat gains were more frequent than losses; (c) longer alleles were found to be more mutable; and (d) the mutation rates differ at some loci between the two ethnic groups. Large worldwide meiotic transmission datasets are still needed to measure allele-specific mutation rates at the STR loci consensually used in forensic genetics.
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http://dx.doi.org/10.1007/s00414-013-0847-2DOI Listing
January 2014

Use of X-linked short tandem repeat loci in routine parentage casework.

Transfusion 2007 Jun;47(6):1050-3

Genomic Engenharia Molecular, São Paulo, SP, Brazil.

Background: Dealing with genetic inconsistencies in parentage testing, especially in motherless cases, remains a continual difficulty.

Study Design And Methods: Four difficult cases, comprising two trios and two duos, were selected from routine parentage testing casework. In these, relatively low combined paternity indices were observed as a result of few discrepant loci that were treated as being due to paternal mutations. An additional eight short tandem repeat (STR) loci along the X chromosome were studied in the alleged father and female child to try and help resolve these cases.

Results: In all four cases, the X chromosome haplotypes in the alleged father were different from those in the child, showing decisively that the alleged father could be excluded from being the biologic father of the child.

Conclusion: In recent times the study of X chromosome haplotypes has been shown to be useful in parentage testing where the alleged father is absent and where only his close relatives are available for testing. This work demonstrates that such studies can also prove valuable in the testing of standard trios and duos in cases where there only a few genetic inconsistencies amongst the loci tested, making it difficult to distinguish between paternal mutations and a close relative of the alleged father being the biologic father.
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http://dx.doi.org/10.1111/j.1537-2995.2007.01238.xDOI Listing
June 2007

Results of the 2003-2004 GEP-ISFG collaborative study on mitochondrial DNA: focus on the mtDNA profile of a mixed semen-saliva stain.

Forensic Sci Int 2006 Jul 21;160(2-3):157-67. Epub 2005 Oct 21.

Instituto Nacional de Toxicología y Ciencias Forenses, Servicio de Biología, Barcelona, Spain.

We report here a review of the seventh mitochondrial DNA (mtDNA) exercise undertaken by the Spanish and Portuguese working group (GEP) of the International Society for Forensic Genetics (ISFG) corresponding to the period 2003-2004. Five reference bloodstains from five donors (M1-M5), a mixed stain of saliva and semen (M6), and a hair sample (M7) were submitted to each participating laboratory for nuclear DNA (nDNA; autosomal STR and Y-STR) and mtDNA analysis. Laboratories were asked to investigate the contributors of samples M6 and M7 among the reference donors (M1-M5). A total of 34 laboratories reported total or partial mtDNA sequence data from both, the reference bloodstains (M1-M5) and the hair sample (M7) concluding a match between mtDNA profiles of M5 and M7. Autosomal STR and Y-STR profiling was the preferred strategy to investigate the contributors of the semen/saliva mixture (M6). Nuclear DNA profiles were consistent with a mixture of saliva from the donor (female) of M4 and semen from donor M5, being the semen (XY) profile the dominant component of the mixture. Strikingly, and in contradiction to the nuclear DNA analysis, mtDNA sequencing results yield a more simple result: only the saliva contribution (M4) was detected, either after preferential lysis or after complete DNA digestion. Some labs provided with several explanations for this finding and carried out additional experiments to explain this apparent contradictory result. The results pointed to the existence of different relative amounts of nuclear and mtDNAs in saliva and semen. We conclude that this circumstance could strongly influence the interpretation of the mtDNA evidence in unbalanced mixtures and in consequence lead to false exclusions. During the GEP-ISFG annual conference a validation study was planned to progress in the interpretation of mtDNA from different mixtures.
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http://dx.doi.org/10.1016/j.forsciint.2005.09.005DOI Listing
July 2006

Mitochondrial DNA error prophylaxis: assessing the causes of errors in the GEP'02-03 proficiency testing trial.

Forensic Sci Int 2005 Mar;148(2-3):191-8

Unidad de Genética, Facultad de Medicina de la Universidad de Santiago de Compostela, Instituto de Medicina Legal, A Coruña, Galicia-Spain.

We report the results of the Spanish and Portuguese working group (GEP) of the International Society for Forensic Genetics (ISFG) Collaborative Exercise 2002-2003 on mitochondrial DNA (mtDNA) analysis. Six different samples were submitted to the participating laboratories: four blood stains (M1-M2-M3-M4), one mixture blood sample (M5), and two hair shaft fragments (M6). Most of the labs reported consensus results for the blood stains, slightly improving the results of previous collaborative exercises. Although hair shaft analysis is still carried out by a small number of laboratories, this analysis yielded a high rate of success. On the contrary, the analysis of the mixture blood stain (M5) yielded a lower rate of success; in spite of this, the whole results on M5 typing demonstrated the suitability of mtDNA analysis in mixture samples. We have found that edition errors are among the most common mistakes reported by the different labs. In addition, we have detected contamination events as well as other minor problems, i.e. lack of standarization in nomenclature for punctual and length heteroplasmies, and indels. In the present edition of the GEP-ISFG exercise we have paid special attention to the visual phylogenetic inspection for detecting common sequencing errors.
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http://dx.doi.org/10.1016/j.forsciint.2004.06.008DOI Listing
March 2005

Results of the GEP-ISFG collaborative study on two Y-STRs tetraplexes: GEPY I (DYS461, GATA C4, DYS437 and DYS438) and GEPY II (DYS460, GATA A10, GATA H4 and DYS439).

Forensic Sci Int 2003 Aug;135(2):158-62

Institute of Legal Medicine, University of Santiago de Compostela, Compostela, Spain.

A collaborative exercise was carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG) in order to evaluate the performance of two Y-chromosome STR PCR tetraplexes, which include the loci DYS461, GATA C4, DYS437 and DYS438 (GEPY I), and DYS460, GATA A10, GATA H4 and DYS439 (GEPY II). The participating laboratories were asked to type three samples for the eight markers, using a specific amplification protocol. In addition, two control samples, with known haplotypes, were provided. The results obtained by the 13 different participating laboratories were identical, except for two laboratories that failed to type correctly the same two samples for GATA C4. By sequence analyses, two different GATA C4 allele structures were found. One control sample (allele 21) and two questioned samples (allele 22, correctly typed by all the laboratories, and allele 25) presented the following repeat structure: (TCTA)4(TGTA)2(TCTA)2(TGTA)2(TCTA)n, but different from the one found for allele 26 in one sample included in this exercise, as well as in the second control sample (allele 23), namely (TCTA)4(TGTA)2(TCTA)2(TGTA)2(TCTA)2(TGTA)2(TCTA)n. The collaborative exercise results proved that both Y-tetraplexes produce good amplification results, with the advantage of being efficiently typed using different separation and detection methodologies. However, since GATA C4 repeat presents a complex structure, with alleles differing in sequence structure, efficient denaturing conditions should be followed in order to avoid typing errors due to sizing problems.
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http://dx.doi.org/10.1016/s0379-0738(03)00200-7DOI Listing
August 2003

Results of the GEP-ISFG collaborative study on the Y chromosome STRs GATA A10, GATA C4, GATA H4, DYS437, DYS438, DYS439, DYS460 and DYS461: population data.

Forensic Sci Int 2003 Aug;135(2):150-7

IPATIMUP, Institute of Pathology and Immunology of University of Porto, Porto, Portugal.

The Spanish and Portuguese ISFG Working Group (GEP-ISFG) carried out a collaborative exercise in order to asses the performance of two Y chromosome STR tetraplexes, which include the loci DYS461, GATA C4, DYS437 and DYS438 (GEPY I), and DYS460, GATA A10, GATA H4 and DYS439 (GEPY II). The groups that reported correct results in all the systems were also asked to analyse a population sample in order to evaluate the informative content of these STRs in different populations. A total of 1020 males out of 13 population samples from Argentina, Brazil, Costa Rica, Macao, Mozambique, Portugal and Spain were analysed for all the loci included in the present study. Haplotype and allele frequencies of these eight Y-STRs were estimated in all samples. The lowest haplotype diversity was found in the Lara (Argentina) population (95.44%) and the highest (99.90%) in Macao (China). Pairwise haplotype analysis showed the relative homogeneity of the Iberian origin samples, in accordance with what was previously found in the European populations for other Y-STR haplotypes (http://www.ystr.org). As expected, the four non-Caucasian samples, Macao (Chinese), Mozambique (Africans), Costa Rica (Africans) and Argentina (Lara, Amerindians), show highly significant Phist values in the pairwise comparisons with all the Caucasian samples.
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http://dx.doi.org/10.1016/s0379-0738(03)00199-3DOI Listing
August 2003

The 2000-2001 GEP-ISFG Collaborative Exercise on mtDNA: assessing the cause of unsuccessful mtDNA PCR amplification of hair shaft samples.

Forensic Sci Int 2003 Jun;134(1):46-53

Comisara General de Policía Científica, Sección de Biología-ADN, Madrid, Spain.

We report the results of Spanish and Portuguese working group (GEP) of International Society of Forensic Genetics (ISFG) Collaborative Exercise 2001-2002 on mitochondrial DNA (mtDNA) analysis. 64 laboratories from Spain, Portugal and several Latin-American countries participated in this quality control exercise. Five samples were sent to the participating laboratories, four blood stains (M1-M4) and a sample (M5) consisting of two hair shaft fragments. M4 was non-human (Felis catus) in origin; therefore, the capacity of the labs to identify the biological source of this sample was an integral part of the exercise. Some labs detected the non-human origin of M4 by carrying out immuno-diffussion techniques using antihuman serum, whereas others identified the specific animal origin by testing the sample against a set of animal antibodies or by means of the analysis of mtDNA regions (Cyt-b, 12S, and 16S genes). The results of the other three human blood stains (M1-M3) improved in relation to the last Collaborative Exercises but those related to hairs yielded a low rate of success which clearly contrasts with previous results. As a consequence of this, some labs performed additional analysis showing that the origin of this low efficiency was not the presence of inhibitors, but the low quantity of DNA present in these specific hair samples and the degradation. As a general conclusion the results emphasize the need of external proficiency testing as part of the accreditation procedure for the labs performing mtDNA analysis in forensic casework.
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http://dx.doi.org/10.1016/s0379-0738(03)00095-1DOI Listing
June 2003