Esther Martínez-Espín

High-activity variants of the uMAOA polymorphism increase the risk for depression in a large primary care sample

Studies on the association between the functional uMAOA polymorphism and depression have yielded non‐conclusive results up till now. One thousand two hundred twenty eight consecutive Spanish primary care attendees, participating in the PREDICT study, agreed to take part in this genetic PREDICT‐Gene study. We explored the association between depression and either high‐activity uMAOA alleles or genotypes. Depression was diagnosed using the Composite International Diagnostic Interview (CIDI) to establish three different depressive outcomes (ICD‐10 Depressive Episode (DE), ICD‐10 Severe Depressive Episode (SDE) and DSM‐IV Major Depression (MD)). uMAOA genetic variation was determined by PCR amplification and subsequent electrophoresis. Crude and adjusted (gender and/or age) odds ratios, with 95% confidence intervals, were calculated for the associations between allele or genotype frequencies and all three depressive outcomes. We found associations between all three depressive phenotypes and either high‐activity alleles or high‐activity genotypes in both sexes. The associations were statistically significant for females but not for males. Testing the same associations on the entire sample (males and females) also yielded significant associations between depression and either high‐activity alleles or high‐activity genotype distribution that were independent of age and/or gender (ICD‐10 DE: OR = 1.98; 95% CI: 1.42–1.77; P = 0.00002; ICD‐10‐SDE: OR = 2.05; 95% CI: 1.38–3.05; P = 0.0002; DSM‐IV MD: OR = 1.91; 95% CI: (1.26–2.91); P = 0.0014). Our results provide fairly consistent evidence that high‐activity variants of the MAOA promoter polymorphism confer a modestly higher risk for depression.

Genetic Identification of Western Mediterranean Sturgeons and its Implication for Conservation

To date, the only native sturgeon species in Western Europe was believed to be Acipenser sturio. However, this species is currently restricted to the Gironde River (Southern France), and it poses serious difficulties for rearing in captivity and for using in recovery programme. Furthermore, it has been questioned whether A. sturio is in fact the only species within the rivers of Western Europe, as A. naccarii, a species previously considered endemic of the Adriatic region, has been reported from the Iberian Peninsula in recent years. Here, we have used forensic techniques to obtain DNA from several museum specimens of sturgeons caught in the Spanish Guadalquivir River and in other European rivers. We analysed DNA sequences from these specimens for five genetic markers (three nuclear and two mitochondrial regions), which were subsequently compared with sequences obtained from A. sturioand A. naccarii. Our study demonstrates that A. naccarii coexists withA. sturio, from the Adriatic Sea to the Iberian Peninsula, a finding that could be taken into account in future sturgeon recovery programmes in Western Europe.

Estudio genetico en el sindrome de QT largo en nuestro medio

Congenital long QT syndrome is mainly caused by mutations in the KCNQ1, KCNH2 and SCN5A genes. The aim of this study was to investigate the prevalence of mutations in these three genes in patients with long QT syndrome or idiopathic ventricular fibrillation seen at our center. The study included nine patients with long QT syndrome and four with idiopathic ventricular fibrillation. The first-degree relatives of genotype-positive probands were also investigated. Missense mutations were found in seven patients with long QT syndrome and two with idiopathic ventricular fibrillation. Overall, 71.4% of mutations were in KCNH2 and 28.6% were in SCN5A. No mutations in KCNQ1 were found. Only two mutations had been previously observed. Mutations were also found in six of the 19 relatives studied. In conclusion, our initial experience shows that genetic testing had a high sensitivity for diagnosing long QT syndrome. Mutations were found most frequently in the KCNH2 gene.

Functional effects of a missense mutation in HERG associated with type 2 long QT syndrome

BACKGROUND Long QT syndrome (LQTS) is characterized by a prolonged QT interval that can lead to severe ventricular arrhythmias (torsades de pointes) and sudden death. Congenital LQTS type 2 (LQT2) is due to loss-of-function mutations in the KCNH2 gene encoding Kv11.1 channels responsible for the rapid component of the delayed rectifier current. OBJECTIVE The purpose of this study was to determine the functional properties of the LQT2-associated mutation p.E637G found in a Spanish family. METHODS Wild-type (WT) and p.E637G Kv11.1 channels were transiently transfected in Chinese hamster ovary cells, and currents were recorded using the patch-clamp technique. RESULTS The p.E637G channels lost inward rectification and K(+) selectivity, generating small but measurable slowly activating, noninactivating currents. These important alterations were corrected neither by cotransfection with WT channels nor by incubation at low temperatures or with pharmacological chaperones. As a consequence of its effects on channel gating, the mutation significantly reduced the outward repolarizing current during the action potential (AP), resulting in a marked lengthening of the duration of a simulated human ventricular AP. CONCLUSION We have identified and characterized an LQT2-associated mutation that through removal of C-type inactivation and reduction of K(+) selectivity causes the QT prolongation observed in the patients carrying the mutation. Moreover, the results obtained demonstrate the importance of the glutamic acid at position 637 for the inactivation process and K(+) selectivity of Kv11.1 channels.

Paraguayan population data on the fifteen STR loci included in the PowerPlex 16 kit.

Blood samples were obtained by venipuncture from unrelated individuals (n = 168) living in Paraguay.

Analysis of Mitochondrial and Nuclear DNA Markers in Old Museum Sturgeons Yield Insights About the Species Existing in Western Europe: A. sturio, A. naccarii and A. oxyrinchus

Today, with all the sturgeon species almost disappearing all over the world, it is necessary to undertake their recovery under the programs for the conservation of genetic resources. The complete absence of these fish from most rivers increases the difficulties in carrying out such programs, hampering the genetic identification of specimens and their correct species assignment. However, with the development of new and reliable molecular genetic techniques, many studies such as this are yielding insights concerning the sturgeon species that inhabited European rivers in the past. In the last few years, our group has developed forensic techniques to isolate DNA from ancient sturgeon specimens preserved in museums. These DNA samples have been the subject of various analyses conducted on several nuclear and mitochondrial DNA markers. The combined use of both types of markers has provided accurate genetic identification of these specimens and has overcome the problem of misinterpretation caused by hybridization and introgression. Here, we show that, in addition to Acipenser sturio (the only species previously believed to inhabit the rivers of Western Europe), two other species, Acipenser naccarii and Acipenser oxyrinchus lived in these rivers. Thus, we have found evidence for the presence of A. naccarii in the Guadalquivir river in the Iberian Peninsula and in some rivers in Italy from the Tyrrhenian/Ligurian side, as well as for the presence of A. oxyrinchus in the Ebro river in Spain. Our studies clarify the distribution of sturgeon species in the Western Mediterranean and open new perspectives for recovery plans.

Forensic Strategies Used for DNA Extraction of Ancient and Degraded Museum Sturgeon Specimens

The procedure for the successful extraction of nucleic acids depends on the type of sample being extracted and the purpose of the extraction. Protocols for the extraction of high copy number DNA samples vary significantly from those of degraded DNA samples. This study involved the development of a DNA extraction protocol that includes a cleaning procedure designed to remove external contaminants (e.g. biological, environmental, or chemical). This protocol, used to test ancient human bones, was used for testing ancient and degraded DNA samples from sturgeons.

Population data of Ecuador for fifteen STR loci (POWERPLEX 16)

Blood samples were obtained by venipuncture from unrelated individuals (n = 150) living in Ecuador.

Spanish population data for the 15 STRs loci included in Powerflex-16

Short tandem repeat (STR) loci are the most informative PCR-based genetic markers available to date for attempting to individualize biological material. The 16 STR loci: D3S1358, TH01, D21S11, D18S51, PentaE, D5S818, D13S317, D7S820, D16S539, CSF1PO, PentaD, vWA, D8S1179, TPOX, FGA, and the locus amelogenin can be amplified simultaneously using the the PowerPlex16 kit (Promega, Madison, WI, USA). This paper presents allele distribution data in the Spanish population. The data demonstrate that these loci can be useful for providing estimates of the frequency of a DNA profile in forensic identity testing and that a multiple locus profile is extremely rare in all the population. Whole blood was obtained in EDTA vacutainer tubes by venipuncture from unrelated individuals (N=323) residing in Andalucia (Spain). Extracted DNA samples were amplified at the 16 loci using the PowerPlex 16 kit (Promega). Samples were analyzed using the ABI Prismk 310 Genetic Analyzer (PE Biosystems, Foster City, CA) according to the manufacturer’s recommended protocol. All 15 loci are highly polymorphic in the Spanish sample population with the locus TPOX (66.8%) having the lowest observed heterozygosity, and the locus D18S51 (87.5%) displaying the highest heterozygosity. The most discriminating loci were D18S51 (PD=0.969) and PentaE (PD=0.968). The combined probability of exclusion for the 15 STR loci is 0.99999953. There was little evidence for departures from Hardy-Weinberg expectations (HWE) in this sample population. Based on the exact test, the locus that departed significantly from HWE was vWA ( p=0.0488). After employing the Bonferroni correction for the number of loci analyzed, these observations are not likely to be significant. An interclass correlation test analysis was performed to detect any correlations

Response to An Expanding Role of Biomarkers in Acute Aortic Syndromes

concluded that the use of genetic and biochem-ical biomarkers in acute aortic syndromes could be a toolfor optimizing the management of this high-risk groupof patients. They also show the relevant role of geneticbiomarkers in early diagnosis of familial disorders likeMarfan syndrome, aortic thoracic aneurysm/dissection,Ehlers-Danlos, and osteogenesis imperfecta syndrome.We believe these biomarkers will be guides to futureclinical diagnoses and accurate diagnosis and prognosis ofcardiovascular diseases, and for that reason we would liketo mention the relevant role of variants that are classifiedas variants of unknown significance (VUS) in Mendeliandisorders such Marfan syndrome. Genetic testing maybenefit patients, at-risk family members, and individualswith borderline phenotypes, as well as improve geneticcounseling and allow critical differential diagnoses.