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.

Characterization of human control region sequences for Spanish individuals in a forensic mtDNA data set.

Population data on the hypervariable regions of the mitochondrial DNA (mtDNA) genome are used to convey the relative rarity of mtDNA profiles obtained from evidence samples and of profiles used to identify missing persons. In this study, mtDNA profiles of Spanish individuals (n=312) were analyzed to describe haplogroup distributions and to determine relevant single nucleotide polymorphisms (SNPs) of those haplogroups. All nine common European haplogroups were observed in the sample, and these were divided into subgroups when possible. Haplogroup H was the most common haplogroup. The haplogroups U, J, T, and V were the next most frequent groups, each occurring at a frequency of 6.4% or greater. In addition, African and Asian sequences were present though rare in the samples. The data were compared with and found to be similar to other published data sets. There were 109 SNPs observed in the data set, including 10 positions not previously reported. The most variable sites are consistent with other studies.

Intentional mixed buccal cell reference sample in a paternity case.

We report a case where an alleged father (AF) attempted to substitute someone else's saliva sample for his reference sample in a paternity analysis. Buccal cells were collected from the AF and the child, and DNA analysis was performed using an autosomal STR loci (Identifiler). The profile from the AF showed extra peaks in some loci, as well as a much higher "X" allele peak relative to the "Y" allele peak at the amelogenin locus. After conducting reanalysis by another technician with another set of positive and negative controls, it was concluded that the only source of the mixed profile was by intentional introduction by the AF, at the time of sampling, of some foreign human biological material, most likely saliva from a woman. Owing to the inconclusive results, when the AF was called back to the lab and the peculiar results were explained to him, he admitted that he had introduced into his mouth saliva from another person in an attempt to be excluded as the father of the child. Although tampering with DNA reference samples is not common, some individuals may attempt to contaminate or otherwise adulterate specimens before DNA tests. Personnel responsible for sampling should be aware of this possibility and should try to establish procedures to avoid the problem.

Undescribed mutations in FBN1 gene in two family cases of Marfan syndrome.

Marfan syndrome (MFS) is a multisystem autosomal dominant heritable disorder and, although there are over 1700 mutations that have been identified in the fibrillin-1 (FBN1) gene associated with it, there are many variants that remain unknown. Here we report two family cases of MFS with two new undescribed variations (C914S and H2426C) in FBN1 gene. Both variations produce alterations in the structural conformation of the protein resulting in pathogenic events in these patients. Finally, this case report includes both pathogenic mutations that have also been clinically and genetically confirmed to result in MFS. This clinical, genetic, and in silico analysis of potentially harmful variations in unrelated MFS patients provides additional evidence for the suggested causative role of the mutations c.2740T > A (C914S), c.7276_7278delCAT (p.H2426C) in FBN1 gene in MFS. .

Surname and Y chromosome in Southern Europe: a case study with Colom/Colombo.

According to most historians, Christopher Columbus was born in Genoa, Italy. However, based on some key facts in the discoverer's biography, as well as in the linguistic analysis of his texts, some historians and linguists believe that Columbus could have been of Catalan origin. A Ligurian Columbus would have carried the Colombo surname, whereas he would have been called Colom if he were Catalan. In order to test whether it would be possible to discriminate between a Ligurian or a Catalan origin were Columbus' Y-chromosome haplotype to be retrieved, we genotyped 17 Y-chromosome STRs in 238 Spanish (from Catalonia, Valencia, and the Balearic Islands) and French Colom men, and 114 North Italian Colombo (from Liguria, Lombardy, and Piedmont). The Italian samples and, in particular, the Lombard Colombos were genetically as diverse as the general population, and we found little evidence of clusters of haplotypes that could indicate descent from a single founder. Colombo is actually the most frequent surname in Lombardy, where foundlings and orphans used to be given the surname Colombo. By contrast, Y-chromosome diversity was reduced in the Iberian Colom, where most of the men had Y chromosomes belonging to a few lineages. This implies that a positive identification would be more likely if Columbus were of Catalan descent. In this study, we have shown the diverse dynamics of two surnames linked by their etymology, in what is, to the best of our knowledge, the first genetic analysis of a surname in Southern Europe.

Genetic testing of patients with long QT syndrome.

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.