Publications by authors named "Alejandro Blanco-Verea"

21 Publications

  • Page 1 of 1

Sudden infant death as the most severe phenotype caused by genetic modulation in a family with atrial fibrillation.

Forensic Sci Int Genet 2019 11 31;43:102159. Epub 2019 Aug 31.

Xenética Cardiovascular, Instituto de Investigación Sanitaria de Santiago de Compostela, Spain; Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Spain; Red de Enfermedades Cardiovasculares (CIBERCV), Spain.

Aims: To assess the functional impact of two combined KCNH2 variants involved in atrial fibrillation, syncope and sudden infant death syndrome.

Methods And Results: Genetic testing of a 4-month old SIDS victim identified a rare missense heterozygous in KCNH2 variant (V483I) and a missense homozygous polymorphism (K897T) which is often described as a genetic modifier. Electrophysiological characterisation of heterologous HERG channels representing two different KCNH2 genotypes within the family, showed significant differences in both voltage and time dependence of activation and inactivation with a global gain-of-function effect of mutant versus wild type channels and, also, differences between both types of recombinant channels.

Conclusions: The rare variant V483I in combination with K897T produces a gain-of-function effect that represents a pathological substrate for atrial fibrillation, syncope and sudden infant death syndrome events in this family. Ascertaining the genotype-phenotype correlation of genetic variants is imperative for the correct assessment of genetic testing and counselling.

Translational Perspective: According to the current guidelines for clinical interpretation of sequence variants, functional studies are an essential tool for the ascertainment of variant pathogenicity. They are especially relevant in the context of sudden infant death syndrome and sudden cardiac death, where individuals cannot be clinically evaluated. The patch-clamp technique is a gold-standard for analysis of the biophysical mechanisms of ion channels.
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http://dx.doi.org/10.1016/j.fsigen.2019.102159DOI Listing
November 2019

Sudden unexpected death in the young - Value of massive parallel sequencing in postmortem genetic analyses.

Forensic Sci Int 2018 Dec 26;293:70-76. Epub 2018 Oct 26.

Institute of Legal Medicine, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.

Cases of sudden cardiac death (SCD) in young and apparently healthy individuals represent a devastating event in affected families. Hereditary arrhythmia syndromes, which include primary electrical heart disorders as well as cardiomyopathies, are known to contribute to a significant number of these sudden death cases. We performed postmortem genetic analyses in young sudden death cases (aged <45years) by means of a defined gene panel using massive parallel sequencing (MPS). The data were evaluated bioinformatically and detected sequence variants were assessed using common databases and applying in silico prediction tools. In this study, we identified variants with likely pathogenic effect in 6 of 9 sudden unexpected death (SUD) cases. Due to the detection of numerous unknown and unclassified variants, interpretation of the results proved to be challenging. However, by means of an appropriate evaluation of the findings, MPS represents an important tool to support the forensic investigation and implies great progress for relatives of young SCD victims facilitating adequate risk stratification and genetic counseling.
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http://dx.doi.org/10.1016/j.forsciint.2018.09.034DOI Listing
December 2018

A Novel Calsequestrin 2 Deletion Causing Catecholaminergic Polymorphic Ventricular Tachycardia and Sudden Cardiac Death.

Rev Esp Cardiol (Engl Ed) 2019 Aug 20;72(8):681-683. Epub 2018 Aug 20.

Xenética Cardiovascular, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain; Servicio de Cardiología, Hospital Clínico Universitario de Santiago de Compostela-SERGAS, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Santiago de Compostela, A Coruña, Spain; Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela -Universidade de Santiago de Compostela- Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, A Coruña, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.rec.2018.07.005DOI Listing
August 2019

Postmortem genetic testing should be recommended in sudden cardiac death cases due to thoracic aortic dissection.

Int J Legal Med 2017 Sep 8;131(5):1211-1219. Epub 2017 Apr 8.

Xenética de Enfermidades Cardiovasculares e Oftalmolóxicas, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain.

Background: Acute thoracic aortic dissections and ruptures, the main life-threatening complications of the corresponding aneurysms, are an important cause of sudden cardiac death. Despite the usefulness of the molecular diagnosis of these conditions in the clinical setting, the corresponding forensic field remains largely unexplored. The main goal of this study was to explore and validate a new massive parallel sequencing candidate gene​ assay as a diagnostic tool for acute thoracic aortic dissection autopsy cases.

Materials And Methods: Massive parallel sequencing of 22 thoracic aortic disease candidate genes performed in 17 cases of thoracic aortic dissection using AmpliSeq and Ion Proton technologies. Genetic variants were filtered by location, type, and frequency at the Exome Aggregation Consortium and an internal database and further classified based on the American College of Medical Genetics and Genomics (ACMG) recommendations published in 2015. All prioritized results were confirmed by traditional sequencing.

Results: From the total of 10 potentially pathogenic genetic variants identified in 7 out of the 17 initial samples, 2 of them were further classified as pathogenic, 2 as likely pathogenic, 1 as possibly benign, and the remaining 5 as variants of uncertain significance, reaching a molecular autopsy yield of 23%, approximately.

Conclusions: This massive parallel sequencing candidate gene approach proved useful for the molecular autopsy of aortic dissection sudden cardiac death cases and should therefore be progressively incorporated into the forensic field, being especially beneficial for the anticipated diagnosis and risk stratification of any other family member at risk of developing the same condition.
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http://dx.doi.org/10.1007/s00414-017-1583-9DOI Listing
September 2017

PRKG1 and genetic diagnosis of early-onset thoracic aortic disease.

Eur J Clin Invest 2016 Sep 18;46(9):787-94. Epub 2016 Aug 18.

Xenética de Enfermidades Cardiovasculares e Oftalmolóxicas, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain.

Background: The 20% of thoracic aortic aneurysms and dissections independent from the main connective tissue syndromes and expected to be familial has gained importance over the past years. The more frequent pattern of inheritance of these nonsyndromic cases is autosomal dominant with incomplete penetrance and variable expression. Although many candidate genes exist, unresolved familial cases suggest still unravelled genetic variation. The main purpose of this study was to establish the genetic diagnosis of one of those.

Materials And Methods: To begin with, we applied a candidate gene approach based on both traditional and a customized massive parallel sequencing panel, followed by Illumina HiSeq 2000 whole exome sequencing of four family members affected by early-onset thoracic aortic disease and two unaffected relatives. We prioritized whole exome sequencing results based on variant location, type and frequency in general population databases and performed segregation analysis in 14 family members using traditional sequencing.

Results: After the negative results we obtained with candidate gene approaches, the analysis and prioritization of whole exome sequencing results brought out the heterozygote c.530G>A:p.Arg177Gln PRKG1 variant (NM_001098512), located in one of the aortic smooth muscle cell contractile apparatus genes. This candidate variant segregated with thoracic aortic disease, as it was present in seven affected and absent in five unaffected family members, further supporting its causality.

Conclusions: This was the second time PRKG1 was associated with thoracic aortic disease, highlighting and reaffirming it as a strong candidate for gene-based diagnosis of nonsyndromic early-onset cases.
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http://dx.doi.org/10.1111/eci.12662DOI Listing
September 2016

Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood.

Arch Dis Child 2015 Oct 13;100(10):952-6. Epub 2015 Aug 13.

Xenética de Enfermidades Cardiovasculares, Instituto de Investigación Sanitaria de Santiago, Red de Investigación Cardiovascular (RIC), Santiago De Compostela, Spain Grupo de Medicina Xenómica, University of Santiago de Compostela, Santiago de Compostela, Spain Fundación Pública Galega de Medicina Xenómica, SERGAS, Santiago de Compostela, Spain.

Objectives: Sudden unexplained death in children is a tragic and traumatic event, often worsened when the cause of death cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of cardiomyopathy, channelopathy and aortic disease associated genes that may have increased these children's vulnerability to sudden cardiac death.

Design: We performed molecular autopsy of 41 cases of sudden unexplained death in infants and children through massive parallel sequencing of up to 86 sudden cardiac death-related genes. Multiple in silico analyses were conducted together with a thorough review of the literature in order to prioritise the putative pathogenic variants.

Results: A total of 63 variants in 35 cases were validated. The largest proportion of these variants is located within cardiomyopathy genes although this would have been more expected of channelopathy gene variants. Subtle microscopic features of heart tissue may indicate the presence of an early onset cardiomyopathy as a predisposing condition to sudden unexpected death in some individuals.

Conclusions: Next-generation sequencing technologies reveal the existence of a wide spectrum of rare and novel genetic variants in sarcomere genes, compared with that of cardiac ion channels, in sudden unexplained death in infants and children. Our findings encourage further investigation of the role of early onset inherited cardiomyopathies and other diseases involving myocardial dysfunction in these deaths. Early detection of variants in these individuals could help to unmask subtle forms of disease within their relatives, who would eventually benefit from better counselling about their genetic history.
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http://dx.doi.org/10.1136/archdischild-2015-308200DOI Listing
October 2015

The relationship between surname frequency and Y chromosome variation in Spain.

Eur J Hum Genet 2016 Jan 22;24(1):120-8. Epub 2015 Apr 22.

Human Evolutionary Genetics Group, Department of Zoology, University of Oxford, Oxford, UK.

In most societies, surnames are passed down from fathers to sons, just like the Y chromosome. It follows that, theoretically, men sharing the same surnames would also be expected to share related Y chromosomes. Previous investigations have explored such relationships, but so far, the only detailed studies that have been conducted are on samples from the British Isles. In order to provide additional insights into the correlation between surnames and Y chromosomes, we focused on the Spanish population by analysing Y chromosomes from 2121 male volunteers representing 37 surnames. The results suggest that the degree of coancestry within Spanish surnames is highly dependent on surname frequency, in overall agreement with British but not Irish surname studies. Furthermore, a reanalysis of comparative data for all three populations showed that Irish surnames have much greater and older surname descent clusters than Spanish and British ones, suggesting that Irish surnames may have considerably earlier origins than Spanish or British ones. Overall, despite closer geographical ties between Ireland and Britain, our analysis points to substantial similarities in surname origin and development between Britain and Spain, while possibly hinting at unique demographic or social events shaping Irish surname foundation and development.
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http://dx.doi.org/10.1038/ejhg.2015.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795233PMC
January 2016

Whole exome sequencing for the identification of a new mutation in TGFB2 involved in a familial case of non-syndromic aortic disease.

Clin Chim Acta 2014 Nov 19;437:88-92. Epub 2014 Jul 19.

Xenética de enfermidades cardiovasculares e oftalmolóxicas, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, A Coruña, Spain; Grupo de Medicina Xenómica IDIS-USC, Fundación Pública Galega de Medicina Xenómica, 15706 Santiago de Compostela, A Coruña, Spain. Electronic address:

Background: Non-syndromic aortic disease (NSAD) is a frequently asymptomatic but potentially lethal disease characterised by familial cases of thoracic aortic aneurysms and dissections. This monogenic but genetically heterogeneous condition is primarily inherited as an autosomal dominant disorder with low penetrance and variable expression. Mutations in ACTA2, TGFBR1, TGFBR2, MYH11, SMAD3, MYLK, and FBN1 genes have been described but still, there are many unresolved familial cases.

Methods: The whole exome of two distantly related and affected members of a Spanish family with multiple cases of NSAD was analysed through 5500 SOLiD(™) System for the identification of shared and putative pathogenic variants.

Results: A new mutation termed c.C1042T:p.R348C (NM_001135599.2) was identified in TGFB2, a gene located in an evolutionary highly conserved region (Chr1: 218,519,577-218,617,961) that has been recently connected to this disease. The analysis of other family members using capillary sequencing confirmed cosegregation of the mutation with the disease and its incomplete penetrance.

Conclusions: The repeated implication of TGFB2 in the development of thoracic aortic aneurysms and dissections suggests that this gene should be considered during genetic diagnosis of this disease. An accurate diagnosis of affected individuals and additional family members at risk allows for a personalised and more efficient gene-based follow-up and treatment. Finally, the reiterative presence of common musculoskeletal and craniofacial additional features in patients with TGFB2 mutations suggests the existence of a new yet undefined connective tissue syndrome responsible for not only aortic dilation, but also for the other extracardiac alterations present in the affected patients.
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http://dx.doi.org/10.1016/j.cca.2014.07.016DOI Listing
November 2014

Next generation sequencing challenges in the analysis of cardiac sudden death due to arrhythmogenic disorders.

Electrophoresis 2014 Nov 6;35(21-22):3111-6. Epub 2014 Aug 6.

Grupo de Xenética de enfermidades cardiovasculares e oftalmolóxicas, IDIS, RIC Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, SERGAS, Santiago de Compostela, Spain.

Inherited arrhythmogenic disorders is a relatively common cause of cardiac sudden death in young people. Diagnosis has been difficult so far due to the genetic heterogeneity of the disease. Next generation sequencing (NGS) is offering a new scenario for diagnosis. The purpose of our study was to validate NGS for the analysis of twenty-eight genes known to be associated with inherited arrhythmogenic disorders and therefore with sudden cardiac death. SureSelect hybridization was used to enrich DNA from 53 samples, prior to be sequenced with the SOLID™ System of Life Technologies. Depth of coverage, consistency of coverage across samples, and location of variants identified were assessed. All the samples showed a depth of coverage over 200×, except one of them discarded because of its coverage below 30×. Average percentage of target bp covered at least 20× was 96.45%. In the remaining samples, following a prioritization process 46 possible variants in 31 samples were found, of which 45 were confirmed by Sanger sequencing. After filtering variants according to their minor allele frequency in the Exome Sequencing Project 27 putative pathogenic variants in 20 samples remained. With the use of in silico tools, 13 variants in 11 samples were classified as likely pathogenic. In conclusion, NGS allowed us to accurately detect arrhythmogenic disease causing mutations in a fast and cost-efficient manner that is suitable for daily clinical and forensic practice of genetic testing of this type of disorders.
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http://dx.doi.org/10.1002/elps.201400148DOI Listing
November 2014

Uniparental markers of contemporary Italian population reveals details on its pre-Roman heritage.

PLoS One 2012 10;7(12):e50794. Epub 2012 Dec 10.

Unidade de Xenética, Facultade de Medicina, Instituto de Medicina Legal, Universidade de Santiago de Compostela, Galicia, Spain.

Background: According to archaeological records and historical documentation, Italy has been a melting point for populations of different geographical and ethnic matrices. Although Italy has been a favorite subject for numerous population genetic studies, genetic patterns have never been analyzed comprehensively, including uniparental and autosomal markers throughout the country.

Methods/principal Findings: A total of 583 individuals were sampled from across the Italian Peninsula, from ten distant (if homogeneous by language) ethnic communities--and from two linguistic isolates (Ladins, Grecani Salentini). All samples were first typed for the mitochondrial DNA (mtDNA) control region and selected coding region SNPs (mtSNPs). This data was pooled for analysis with 3,778 mtDNA control-region profiles collected from the literature. Secondly, a set of Y-chromosome SNPs and STRs were also analyzed in 479 individuals together with a panel of autosomal ancestry informative markers (AIMs) from 441 samples. The resulting genetic record reveals clines of genetic frequencies laid according to the latitude slant along continental Italy--probably generated by demographical events dating back to the Neolithic. The Ladins showed distinctive, if more recent structure. The Neolithic contribution was estimated for the Y-chromosome as 14.5% and for mtDNA as 10.5%. Y-chromosome data showed larger differentiation between North, Center and South than mtDNA. AIMs detected a minor sub-Saharan component; this is however higher than for other European non-Mediterranean populations. The same signal of sub-Saharan heritage was also evident in uniparental markers.

Conclusions/significance: Italy shows patterns of molecular variation mirroring other European countries, although some heterogeneity exists based on different analysis and molecular markers. From North to South, Italy shows clinal patterns that were most likely modulated during Neolithic times.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0050794PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519480PMC
June 2013

Sarcomeric gene mutations in sudden infant death syndrome (SIDS).

Forensic Sci Int 2012 Jun 22;219(1-3):278-81. Epub 2012 Feb 22.

Genetics of Cardiovascular and Ophthalmologic Diseases, Hospital-University Complex of Santiago (CHUS), Santiago de Compostela, Spain.

In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS. The presence of a genetic mutation in the sarcomeric protein usually affects the force of contraction of the myocyte, whose weakness is compensated with progressive hypertrophy and disarray. However, it is unclear whether in the most incipient forms, that is, first years of life, the lack of these phenotypes still confers a risk of arrhythmogenesis. The main goal of the present study is to wonder whether genetic defects in the sarcomeric proteins, previously associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS cases for the most common genes implicated in HCM in adults. A total of 680 mutations localised in 16 genes were analysed by semi-automated matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using the Sequenom MassARRAY(®) System. Ten subjects with completely normal hearts showed mutated alleles at nine of the genetic variants analysed, and one additional novel mutation was detected by conventional sequencing. Therefore, a genetic mutation associated with HCM may cause sudden cardiac death in the absence of an identifiable phenotype.
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http://dx.doi.org/10.1016/j.forsciint.2012.01.018DOI Listing
June 2012

Prevalence of HCM and long QT syndrome mutations in young sudden cardiac death-related cases.

Int J Legal Med 2011 Jul 16;125(4):565-72. Epub 2011 Apr 16.

Genetics of Cardiovascular and Ophthalmologic Diseases, Hospital-University Complex of Santiago (CHUS), Santiago de Compostela, Spain.

Cardiomyopathies and channelopathies are major causes of sudden cardiac death. The genetic study of these diseases is difficult because of their heterogenic nature not only in their genetic traits but also in their phenotypic expression. The purpose of the present study is the analysis of a wide spectrum of previously known genetic mutations in key genes related to hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), and Brugada syndrome (BrS) development. The samples studied include cases of sudden cardiac death (SCD) in young adults and their relatives in order to identify the real impact of genetic screening of SCD in forensic cases. Genetic screening of described variation in 16 genes implicated in the development of HCM and three more genes implicated in LQTS and BrS was performed by using MassARRAY technology. In addition, direct sequencing of the two most prevalent genes implicated in the development of SQTL type 1 and 2 was also carried out. Genetic screening allowed us to unmask four possibly pathogenic mutation carriers in the 49 SCD cases considered; carriers of mutation represent 9% (2/23) of the probands with structural anomalies found after autopsy and 7% (1/14) of the probands with structurally normal hearts after in depth autopsy protocol. One mutation was found among 12 of the recovered SCD cases considered. In people with direct family history of sudden cardiac death, but not themselves, 11 additional mutation carriers were found. Three different mutations were found in six of the 19 LQTS patients, representing three families and two different mutations were found among six patients with previous syncope. Genetic analysis in sudden cardiac death cases could help to elucidate the cause of death, but it also can help in the prevention of future deaths in families at risk. The study presented here shows the importance and relevance of genetic screening in patients with signs of cardiac hypertrophy and in family cases with more than one relative affected.
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http://dx.doi.org/10.1007/s00414-011-0572-7DOI Listing
July 2011

Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy.

Ann Clin Lab Sci 2010 ;40(3):285-9

Hospital-University Complex of Santiago, Santiago de Compostela, Spain.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac hypertrophy caused by mutations in sarcomere protein genes. MYBPC3 mutations are reported as a frequent cause of HCM. We aimed to identify the gene mutation underlying HCM in an Italian patient and his family composed of 13 relatives. Mutation screening of 658 known mutations was performed using a rapid and efficient mutation detection system based on semiautomated MALDI-TOF mass spectrometry using the Sequenom MassArray System and iPLEX Gold genotyping chemistry. Subsequently, direct sequencing of the coding exons and flanking intronic regions was performed for the most suitable HCM genes (MYBPC3, MYH7, TNNT2, TNNI3, and TPM1) in the index patient. We found a novel MYBPC3 gene mutation: G13999T (Gln689His). No other sarcomere gene mutation was found in this family. This genetic variant, which changes the last amino acid of MYBPC3 exon 21, affects a highly conserved residue. Furthermore, the Gln689His does not appear in public databases and has never been described as a polymorphism. The potential pathogenic role of this novel mutation was underlined by its absence in a sample of healthy subjects (n = 122) from the general Italian population. In summary, a novel MYBPC3 gene mutation has been identified in a patient affected by HCM, whereas it was absent in 244 reference alleles.
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November 2010

Ancestry analysis in the 11-M Madrid bomb attack investigation.

PLoS One 2009 Aug 11;4(8):e6583. Epub 2009 Aug 11.

Forensic Genetics Unit, Institute of Legal Medicine, University of Santiago de Compostela, Santiago de Compostela, Galicia, Spain.

The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR) profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a critical part of the investigation and was instigated to help refine the search for further suspects. Although mitochondrial DNA (mtDNA) and Y-chromosome markers routinely demonstrate informative geographic differentiation, the populations compared in this analysis were known to show a proportion of shared mtDNA and Y haplotypes as a result of recent gene-flow across the western Mediterranean, while any two loci can be unrepresentative of the ancestry of an individual as a whole. We based our principal analysis on a validated 34plex autosomal ancestry-informative-marker single nucleotide polymorphism (AIM-SNP) assay to make an assignment of ancestry for DNA from seven unmatched case samples including a handprint from a bag containing undetonated explosives together with personal items recovered from various locations in Madrid associated with the suspects. To assess marker informativeness before genotyping, we predicted the probable classification success for the 34plex assay with standard error estimators for a naïve Bayesian classifier using Moroccan and Spanish training sets (each n = 48). Once misclassification error was found to be sufficiently low, genotyping yielded seven near-complete profiles (33 of 34 AIM-SNPs) that in four cases gave probabilities providing a clear assignment of ancestry. One of the suspects predicted to be North African by AIM-SNP analysis of DNA from a toothbrush was identified late in the investigation as Algerian in origin. The results achieved illustrate the benefit of adding specialized marker sets to provide enhanced scope and power to an already highly effective system of DNA analysis for forensic identification.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006583PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719087PMC
August 2009

The genetic male component of two South-Western Colombian populations.

Forensic Sci Int Genet 2009 Mar 8;3(2):e59-61. Epub 2008 Aug 8.

Pediatrics Department, College of Medicine, University of Cauca, Popayán, Colombia.

In the recent history of Colombia, two factors have contributed to change the population structure, the Spanish conquest and the slave trading promoted principally by Portugal, England and Spain. As a consequence the native population of Colombia has been reduced and mixed with the European and African arriving groups. To assess the male ancestry of the Cauca population, we have examined the frequency of the major Y-chromosome lineages by typing 30 Y-SNPs in two populations from this region: 105 Afro-Colombian individuals and 110 Caucasian-Mestizo individuals. Among the 33 haplogroups defined with the SNPs analysed, 15 haplogroups were detected, 10 of them being shared by both populations. In order to investigate how the level of admixture is, and to compare the genetic background with other neighbour populations, other South American samples previously published were used for comparative analysis.
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http://dx.doi.org/10.1016/j.fsigen.2008.06.006DOI Listing
March 2009

Moors and Saracens in Europe: estimating the medieval North African male legacy in southern Europe.

Eur J Hum Genet 2009 Jun 21;17(6):848-52. Epub 2009 Jan 21.

Department of Zoology, University of Oxford, Oxford, UK.

To investigate the male genetic legacy of the Arab rule in southern Europe during medieval times, we focused on specific Northwest African haplogroups and identified evolutionary close STR-defined haplotypes in Iberia, Sicily and the Italian peninsula. Our results point to a higher recent Northwest African contribution in Iberia and Sicily in agreement with historical data. southern Italian regions known to have experienced long-term Arab presence also show an enrichment of Northwest African types. The forensic and genomic implications of these findings are discussed.
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http://dx.doi.org/10.1038/ejhg.2008.258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947089PMC
June 2009

Phylogenetic evidence for multiple independent duplication events at the DYS19 locus.

Forensic Sci Int Genet 2007 Dec 20;1(3-4):287-90. Epub 2007 Jul 20.

Department of Zoology, University of Oxford, Tinbergen Building, South Parks Road, OX1 3PS Oxford, UK.

Duplication events at Y chromosome STR loci have been repeatedly described in human populations. DYS19 is probably the best known example and it exhibits duplicate state in individuals from all continents. Despite the large amount of available data, evolutionary relationship between DYS19 duplication-bearing chromosomes has not been so far investigated. We address the genealogical correlation among such chromosomes by analysing newly identified DYS19 duplicated Y chromosomes by SNP genotyping and microsatellite-based network analysis. SNP and network analysis show that DYS19 duplicated Y chromosomes associate with different Y chromosome lineages. These results indicate that DYS19 duplication occurred more than once during human evolution.
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http://dx.doi.org/10.1016/j.fsigen.2007.06.001DOI Listing
December 2007

Introduction of an single nucleodite polymorphism-based "Major Y-chromosome haplogroup typing kit" suitable for predicting the geographical origin of male lineages.

Electrophoresis 2005 Dec;26(23):4411-20

Institute of Legal Medicine, National Genotyping Center (CEGEN), University of Santiago de Compostela, Spain.

The European Consortium "High-throughput analysis of single nucleotide polymorphisms for the forensic identification of persons--SNPforID", has performed a selection of candidate Y-chromosome single nucleotide polymorphisms (SNPs) for making inferences on the geographic origin of an unknown sample. From more than 200 SNPs compiled in the phylogenetic tree published by the Y-Chromosome Consortium, and looking at the population studies previously published, a package of 29 SNPs has been selected for the identification of major population haplogroups. A "Major Y-chromosome haplogroup typing kit" has been developed, which allows the multiplex amplification of all 29 SNPs in a single reaction. Allele genotyping was performed with a single base extension reaction (minisequencing) detected by CE. The validation of the multiplex was performed in a total of 1126 unrelated males distributed among 12 worldwide populations. The approach takes advantage of the specific geographic distribution of the Y-chromosome haplogroups and demonstrates the utility of binary polymorphisms to infer the origin of a male lineage.
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http://dx.doi.org/10.1002/elps.200500293DOI Listing
December 2005

Duplications of the Y-chromosome specific loci P25 and 92R7 and forensic implications.

Forensic Sci Int 2004 Mar;140(2-3):241-50

Department of Forensic Genetics, Institute of Forensic Medicine, University of Copenhagen, 11 Frederik V's Vej, DK-2100 Copenhagen, Denmark.

In the present study, we demonstrate that two commonly used Y-chromosome single nucleotide polymorphisms (SNPs), P25 and 92R7, are paralogous sequence variants (PSVs) originating from segmental duplications and that at least one of the sequence variants in each group of loci is polymorphic. Several methodologies were used in order to detect the SNP alleles and the PSVs of the loci. All results obtained with the various typing techniques supported the conclusion. The allele distributions of the binary markers were analysed in more than 600 males with seven different haplogroups. For P25, the ancestral allele C was found in several samples from different haplogroups. The derived allele A was always present with an additional C variant. Haplogroup P was defined by the derived allele A at the 92R7 locus. However, the ancestral allele G was always associated with an A variant due to the duplication.
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http://dx.doi.org/10.1016/j.forsciint.2003.11.035DOI Listing
March 2004