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Angel Carracedo

Publications and source records attributed to Angel Carracedo.

At least 55 records · Page 3Linked to original sources
PubMed2004

mtDNA mutations in tumors of the central nervous system reflect the neutral evolution of mtDNA in populations.

Mitochondrial DNA (mtDNA) instability has been observed in different types of cancer, including colorectal, breast, and gastric cancer. The relationship between the occurrence of such alteration and the nuclear microsatellite instability (nMI) status of the neoplastic cells remains controversial. In an attempt to clarify this issue, we sequenced the first and second mtDNA hypervariable regions, and typed the mitochondrial (CA)(n) dinucleotide polymorphism in 69 patients with primary tumors of the central nervous system (CNS), previously screened for nMI. Tumor samples showed 27 D-loop sequence changes (39.1%) compared to the corresponding blood samples. Microsatellite homoplasmic allele mutations were detected in four cases (5.8%). We did not find significant associations of the mtDNA instability status with clinicopathological parameters including sex, age, tumor size, and duration of clinical course. Neither did we find any association between mtDNA and nuclear instabilities, indicating that, at least in CNS tumors, they respond to different DNA repair mechanisms. We have also compiled the mtDNA instabilities previously reported by other authors for several types of tumors, comparing them to mtDNA polymorphisms in human populations. Most of the tumor-associated changes are common human polymorphisms and mutational hotspots. To explain the molecular behavior of mtDNA instability in tumors, we propose a model also common to other biological situations.

Central Nervous System Neoplasms↗
PubMed2004

The African diaspora: mitochondrial DNA and the Atlantic slave trade.

Between the 15th and 19th centuries ad, the Atlantic slave trade resulted in the forced movement of approximately 13 million people from Africa, mainly to the Americas. Only approximately 11 million survived the passage, and many more died in the early years of captivity. We have studied 481 mitochondrial DNAs (mtDNAs) of recent African ancestry in the Americas and in Eurasia, in an attempt to trace them back to particular regions of Africa. Our results show that mtDNAs in America and Eurasia can, in many cases, be traced to broad geographical regions within Africa, largely in accordance with historical evidence, and raise the possibility that a greater resolution may be possible in the future. However, they also indicate that, at least for the moment, considerable caution is warranted when assessing claims to be able to trace the ancestry of particular lineages to a particular locality within modern-day Africa.

Black People↗
PubMed2004

The EDNAP mitochondrial DNA population database (EMPOP) collaborative exercises: organisation, results and perspectives.

This paper presents an overview of the organisation and the results of the collaborative exercises (CE) of the European DNA Profiling (EDNAP) Group's mitochondrial DNA population database project (EMPOP). The aim of the collaborative exercises was to determine whether uniformity of mtDNA sequencing results could be achieved among different laboratories. These were asked to sequence either the complete mtDNA control region or the two hypervariable regions HVI (16024-16365) and HVII (73-340) from DNA extracts, buccal swabs or bloodstains, proceeding in accordance with the protocol and strategies used in each individual laboratory. The results of the collaborative exercises were employed to identify possible sources of errors that could arise during the analysis and interpretation of mtDNA profiles. These findings were taken as a basis to tentatively make suitable arrangements for the construction of a high quality mtDNA database. One hundred fifty mtDNA profiles were submitted to the evaluating laboratory, and disaccording profiles were classified into four groups corresponding to the source of error: clerical errors, sample mix-ups, contaminations and discrepancies with respect to the mtDNA nomenclature. Overall, 14 disaccording haplotypes (16 individual errors) were observed. The errors included 10 clerical errors, 3 interpretation problems, 2 cases of sample mix-up and 1 case of point heteroplasmic mixture, where the 2 sequencing reactions brought inconsistent base calls. This corresponds to an error rate of 10.7% in a virtual mtDNA database consisting of the collaborative exercise results. However, this estimate is still conservative compared to conclusions drawn by authors of meanwhile numerous publications critically reviewing published mtDNA population databases. Our results and earlier published concerns strongly emphasize the need for appropriate safety regulations when mtDNA profiles are compiled for database purposes in order to accomplish the high standard required for mtDNA databases that are used in the forensic context.

Clinical Laboratory Techniques↗
PubMed2004

Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects.

OBJECTIVE: The A allele of the PD1.3 single-nucleotide polymorphism (SNP) on the programmed cell death gene PDCD1 was markedly more frequent in patients with systemic lupus erythematosus (SLE) than in unaffected controls in a recent study involving large sets of Swedish, European American, and Mexican families. This study sought to determine the role of PDCD1 in susceptibility to SLE in the Spanish population. METHODS: Seven PDCD1 SNPs were studied in 518 SLE patients and 800 healthy control subjects who had been recruited in 5 distant towns spanning continental Spain. Patients and controls were of Spanish ancestry. The diagnosis of SLE was in accordance with the American College of Rheumatology updated classification criteria. RESULTS: The A allele of the PD1.3 polymorphism was significantly less frequent in Spanish female patients with SLE than in Spanish female controls (9.0% versus 13.0%, odds ratio 0.67, 95% confidence interval 0.50-0.89). This difference was consistent across the 5 sets of samples grouped by town of recruitment. The other PDCD1 SNPs were not associated with SLE susceptibility. The haplotype structure of PDCD1 in the Spanish controls was different from that reported in other healthy control populations. CONCLUSION: Our results confirm the association of PDCD1 with susceptibility to SLE, but the findings show a lack of involvement of the PD1.3 SNP, which is contrary to the role of the PD1.3 A allele observed previously. These contradictory results probably reflect population differences in the haplotype structure of the PDCD1 locus. More research focusing on new polymorphisms and identifying associations in other populations will be needed to clarify the role of PDCD1 in SLE susceptibility.

Alleles↗
PubMed2003

Y-chromosome STR haplotypes in Córdoba (Argentina).

Eight Y-chromosome STRs were investigated in a male population sample from Córdoba region (Argentina). Complete Y-chromosomal STRs haplotypes were obtained in 100 individuals, among which 91 different haplotypes were observed. The most common haplotype was shared by 4% of the sample, while 86 haplotypes were unique. The gene diversity was 0.9875 and the discrimination capacity was 0.8600. The combined polymorphism provides a powerful discrimination tool for routine forensic applications.

Argentina↗
PubMed2003

Analysis of the CODIS autosomal STR loci in four main Colombian regions.

Genotype polymorphism studies at the 13 loci STRs included in the combined DNA index system [CODIS and PCR-based short tandem repeat loci, in: Proceedings of the Second European Symposium on Human Identification, Promega Corporation, Madison, WI, 1998, pp. 73-88; J. Forensic Sci. 46 (2001) 453] (CODIS: D3S1358, HUMvWA31, HUMFGA, D8S1179 D21S11, D18S51, D5S818, D13S317, D7S820, HUMTH01, HUMTPOX, HUMCSF1PO and D16S539) were carried out in a sample of 1429 unrelated Colombian individuals belonging to 25 different departments. As many other countries in Latino-America, Colombia shows an important admixture component, basically integrated by Amerindians, European-descendants and African-descendants. Due to the fact that only partial population analyses have been carried out in the country, the main aim of the present analysis is to establish a database of forensic interest based on the widely used CODIS systems covering the main Colombian regions.

Colombia↗
PubMed2003

Testing for kinship in a subdivided population.

The effect of population subdivision on the determination of kinship of any two persons is investigated in this paper. Expressions of the joint genotype probabilities and likelihood ratios on kinship testing are reported. Two real cases are analysed using the Hong Kong Chinese population data and the Spanish data. Various kinds of relationships are investigated for illustration.

Child↗
PubMed2003

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.

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.

Chromosomes, Human, Y↗
PubMed2003

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).

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.

Alleles↗
PubMed2003

Spanish population data and forensic usefulness of a novel Y-STR set (DYS437, DYS438, DYS439, DYS460, DYS461, GATA A10, GATA C4, GATA H4).

DNA typing of 8 recently described STRs on the Y chromosome was carried out by means of 2 multiplex amplification reactions for 134 unrelated males from Cantabria, a region in northern Spain. Multiplex 1 included loci DYS460 (GATA A7.1), GATA A10, GATA H4 and DYS439; multiplex 2 included DYS461 (GATA A7.2), GATA C4, DYS437 and DYS438. Haplotype diversity was found to be 99.36%, similar to that obtained with the standard 9-STR set ("minimal haplotype") of the European Y-user group (99.35%). The 13-locus haplotype resulting from the combination of the standard minimal haplotype and the 4-locus multiplex 1 showed a 99.89% diversity. Further inclusion of the 4 loci in multiplex 2 resulted in a haplotype diversity of 99.93%. The combination of the "minimal haplotype" and the multiplex 1 in the present study may be an efficient way of increasing the power of discrimination in forensic cases.

Alleles↗
PubMed2003

Significance of micro-geographical population structure in forensic cases: a bayesian exploration.

We studied the influence of population structure at the microgeographical level on the analysis of forensic cases. A total of nine autosomal STRs and seven Y-STRs were analyzed in the general mixed population and in two relatively isolated valleys of Cantabria, a region in Northern Spain. Statistically significant differences existed in the frequency distribution of four autosomal STRs, with an overall Fst value of 0.3%. A simulation of virtual trio cases revealed that it did not have a practical influence on the analysis of paternity disputes. Significant differences also existed in most Y-STRs, with an overall Fst value of 3%. Thus, using the general database instead of the specific valley database resulted in 5-fold or higher overestimation of the likelihood ratio of matching in up to 30% of cases. A bayesian analysis revealed that this had a significant impact on the estimation of the probability of identity in scenarios of low "a priori" odds of suspicion.

Alleles↗
PubMed2003

Bimodal allele frequency distribution at Y-STR loci DYS392 and DYS438: no evidence for a deviation from the stepwise mutation model.

A deviation from the stepwise mutation model (SMM) has been suggested for the trinucleotide Y-STR locus DYS392, based upon its bimodal allele frequency distribution in various populations. The same type of distribution is also observed for the pentanucleotide Y-STR DYS438. In order to verify whether a departure from an SMM is likely for these two loci, we studied a large number of Portuguese male DNA samples typed for the two loci and in addition, for the Y-STR loci DYS19, DYS389I/II, DYS390, DYS391 and DYS393. The compatibility of the observed allele frequency spectrum with an SMM was assessed by an apportionment of the molecular variance among, and consideration of the molecular distances between, haplotype groups defined according to their allelic state at each of the two markers of interest. For haplotypes carrying either modal alleles 11 or 13 of DYS392, 18.6% of the molecular variance of the remaining Y-STR background could be attributed to variation between the two groups. When all pairwise Phi(st) values between haplotype groups were compared, group 12 was found to be closer to 11 than to 13, and group 14 was much closer to 13 than to 12 and 11. It may therefore be concluded that DYS392 allele 13 represents an evolutionary lineage with little or no relationship to 11 and 12. Furthermore, allele 14 is a one-step neighbour of 13 and is therefore likely to represent an offshoot from group 13. For haplotypes carrying either modal allele 10 or modal allele 12 of DYS438, 27.7% of the molecular variance of the Y-STR background was found to be due to variation between the two groups. Comparison of the other pairwise Phi(st) values indicated that group 10 was closer to 9 and 11 than to 12, and that group 12 was closer to 11 and 13 than to 10. The lineages defined by the two modal alleles of DYS438 therefore also seem to be phylogenetically distant. When the two loci were analysed in combination, using the standardised linkage disequilibrium measure (D'), a strong association was noted between alleles DYS392*11 and DYS438*10 (D'=0.70) and between DYS392*13 and DYS438*12 (D'=0.72). Taken together, these results show that the bimodal allele frequency distributions of DYS392 and DYS438 are explicable in terms of (probably the same) historical and demographic causes, rather than a mutational mechanism other than SMM. The loci do therefore not appear to warrant any special attention when applied in population genetic or forensic studies.

Chromosomes, Human, Y↗
PubMed2003

Grouping of Y-STR haplotypes discloses European geographic clines.

Y-STR haplotypes are widely studied in Europe and an extensive databasing effort has been conducted (http://www.ystr.org). The distribution of these haplotypes has been considered to present no evidence for substructure at central and southern European level. This picture contrasts with the one that results from Y haplogroups defined by binary markers. This paradox has been solved by admitting that the high STR mutation rate and corresponding recurrence has erased geographic structuration. This explanation prompted us to reanalyse Y-STR haplotypes distribution bearing in mind the commonly admitted model for the generation of diversity in these markers, namely the stepwise mutation model (SMM) and, thus, taking the molecular distance between haplotypes into consideration. Accordingly, we have studied the European distribution of the two most frequent haplotypes in the Iberian Peninsula and their one step neighbours using the European samples deposited in the Y STR database (http://www.ystr.org). For the first group we found a clear-cut decreasing W-E gradient, while for the second the highest frequencies were found in the Iberian Peninsula (3.98% in Portugal and 3.85% in Spain), dropping to 2.88% in France and showing a less well defined SW-NW gradient. Furthermore, we have tested the agreement between haplotype groups and binary markers haplogroups in a random sample of 292 individuals from Northern Portugal. Our results demonstrate that (a) Y-STR haplotype data can be used for wide-scale anthropological approaches disclosing information that has been considered only available through binary markers and (b) forensic use of continental databases needs careful refinement, due to the macro-geographic pattern now evidenced.

Chromosomes, Human, Y↗
PubMed2003

DNA mixtures in forensic casework: a 4-year retrospective study.

Occasionally interpretation guidelines from validation studies are difficult to apply to real forensic casework, especially in the case of mixed samples. Exogenous contamination, an unknown number of contributors or unbalanced proportion of each one in the sample and a varied degree of degradation of the biological materials, contribute to the difficulties in the interpretation of sample profiles. In this paper we have reviewed all the mixed genetic STR profiles encountered in our laboratory over 4 years (1997-2000) and evaluated the problems in the interpretation of the results. From 1547 criminal cases with 2424 samples typed, 163 showed a mixed profile (6.7%). We have observed that occasionally, a mixture appeared in the same sample with one multiplex amplification kit (e.g. Blue) and not with another (e.g. Green). From our results, it can be suggested that technical characteristics of the different fluorochrome groups in the multiplexes override the molecular characteristics of each STR in their capacity to detect mixtures.

DNA Fingerprinting↗