Rosario Calderón

Anthropology of the apolipoprotein E (apo E) gene: low frequency of apo E4 allele in Basques and in tribal (Baiga) populations of India

The distribution of apolipoprotein E (apo E) polymorphism was examined in 11 population groups not previously studied for this system. There is a marked difference in phenotype and gene frequency between the populations of England and Spain. The south European populations of Basques and Spanish non-Basques showed greater similarity to the populations of South Asia. The study clearly indicates that the distribution of apo E alleles does match with regions showing a high mortality rate of coronary heart disease. The data presented also indicate that authochthon groups such as Basques in Europe and tribals in India may throw better light on the role of apolipoproteins in the regulation of lipid levels in disease.

Opportunity for Natural Selection in a Basque Population and Its Secular Trend: Evolutionary Implications of Epidemic Mortality

Analysis of the interaction between mortality patterns and opportunity for natural selection could help to elucidate potential evolutionary implications of epidemic mortality. In this paper secular trends are studied in relation to Crows index (It) and its components of mortality (Im) and fertility (If), using parish records for family reconstitution in a Basque population. A principal components analysis (91% of the variance accounted for) showed marked quantitative and qualitative variations of Im and If depending on the stage of demographic transition of the population analyzed: In pretransitional societies the opportunity for natural selection is determined mainly by differential prereproductive mortality, whereas in posttransitional societies selection resulting from differential fertility plays a key role. The highest values for the mortality component (range 0.81-1.26) and for the relative contribution of Im to It (range 47.1-57.2%) were observed in periods with a high incidence of infectious diseases and when the most severe mortality crises were detected (1830-1859, 1860-1889, and 1890-1919). A differential incidence of epidemic mortality was also found at prereproductive ages (before 16 years) and at reproductive ages (16-45 years), which provides strong support for the idea of the long-term genetic consequences of mortality crises.

A genome-wide association study identifies multiple loci for variation in human ear morphology

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.

Microsatellite DNA markers from HLA region (D6S105, D6S265 and TNFa) in autochthonous Basques from Northern Navarre (Spain).

Background : The extent of the genetic polymorphism of the HLA complex is becoming well characterized in Basque population and their subpopulations. This level of knowledge mainly concerns HLA class I loci. However, Basque population surveys dealing with HLA class II genes and/or microsatellites in the HLA region are still very scarce. Aim : The population genetics of three highly polymorphic short tandem repeat (STR) loci, D6S105, D6S265 and TNFa, from HLA region has been analysed in autochthonous (indigenous) Basques from Northern Navarre (Spain). The same blood samples have been typed for HLA class II genes from DQ/DR/DP regions and some findings from that information can be found therein. Subjects and methods : Blood samples were taken from 107 unrelated autochthonous Basques from Northern Navarre. The criterion used to define Northern Navarrese identity was that of three generations of Basque surnames and birthplaces. Results : The main features observed in Navarrese Basques were the rather high frequencies of alleles D6S105*4 and D6S265*7. A novel allele has been detected at the D6S265 locus (13: 145 bp). The most frequent haplotype was D6S105*8-D6S265*4 with a highly significant linkage disequilibrium being presented. The high frequency of allele TNFa*1 in Basques is noteworthy and this characteristic is not shared by other European populations, where TNFa*1 is absent or shows negligible values. The multidimensional scaling analysis (MDS) for TNFa allele frequencies has shown a high variability among populations and that alleles TNFa*1 ( F ST = 0.0615) and TNFa*12 ( F ST = 0.0424) seem to have significant influence over the spatial population configuration. TNFa*2 showed the lowest FST value (0.0077) because of its conspicuous homogeneous distribution all over the European populations. Conclusions : Findings shown here on HLA microsatellites and their relationships with other HLA class I and class II genes in Basques can be helpful for those studies mainly addressed at detecting associations between HLA genes and diseases in the Basque area as a whole, and particularly in its autochthonous population, settled there since remote times.

Human maternal heritage in Andalusia (Spain): its composition reveals high internal complexity and distinctive influences of mtDNA haplogroups U6 and L in the western and eastern side of region

BackgroundThe archeology and history of the ancient Mediterranean have shown that this sea has been a permeable obstacle to human migration. Multiple cultural exchanges around the Mediterranean have taken place with presumably population admixtures. A gravitational territory of those migrations has been the Iberian Peninsula. Here we present a comprehensive analysis of the maternal gene pool, by means of control region sequencing and PCR-RFLP typing, of autochthonous Andalusians originating from the coastal provinces of Huelva and Granada, located respectively in the west and the east of the region.ResultsThe mtDNA haplogroup composition of these two southern Spanish populations has revealed a wide spectrum of haplogroups from different geographical origins. The registered frequencies of Eurasian markers, together with the high incidence and diversification of African maternal lineages (15% of the total mitochondrial variability) among Huelva Andalusians when compared to its eastwards relatives of Granada and other Iberian populations, constitute relevant findings unknown up-to-date on the characteristics of mtDNA within Andalusia that testifies a female population substructure. Therefore, Andalusia must not be considered a single, unique population.ConclusionsThe maternal legacy among Andalusians reflects distinctive local histories, pointing out the role of the westernmost territory of Peninsular Spain as a noticeable recipient of multiple and diverse human migrations. The obtained results underline the necessity of further research on genetic relationships in both sides of the western Mediterranean, using carefully collected samples from autochthonous individuals. Many studies have focused on recent North African gene flow towards Iberia, yet scientific attention should be now directed to thoroughly study the introduction of European genes in northwest Africa across the sea, in order to determine its magnitude, timescale and methods, and to compare them to those terrestrial movements from eastern Africa and southwestern Asia.

HLA frequencies in Basques in Spain and in neighbouring populations

HLA antigen and gene frequencies at the A, B, and C loci are examined in a sample of 181 Basques and 102 non-Basques in Bilbao, Spain. The most common associations of genes at the A and B loci are as in western Europe generally. The results are compared with gene frequencies in other Basque and non-Basque samples in Spain and France. There is clear distinction in gene frequency between Basques and non-Basques, to which the greatest contribution is made by A1 and B35, followed by B7, B8 and B12; and a difference between Basques in France and in Spain, notably in A28, 29, 30 and 31 and B17 and 18.

Analyzing the genetic structure of the Tepehua in relation to other neighbouring Mesoamerican populations. A study based on allele frequencies of STR markers.

We report data on the genetic variation of the Tepehua population based on 15 autosomal microsatellites. The Tepehua, whose language belongs to the Totonac family, are settled throughout the Sierra Madre Oriental in Mexico and constitute a group in demographic decline. The results suggest that the Tepehua population remained isolated throughout a large part of its history. Phylogenetic analyses performed with other indigenous and admixed populations of Mesoamerica allow us to address their biological history. The results suggest a genetic affinity between the Tepehua and the Huastecos due to their previous shared history, and a certain degree of differentiation from the Otomões groups and the Choles (who are of Mayan origin). A clear genetic differentiation is also apparent between native and admixed populations within the greater region of Mesoamerica. It is currently accepted that the genetic composition of the American populations fits a trihybrid model of admixture. The genetic structure based on comparison of 34 populations throughout the continent (9 indigenous and 23 admixed) using hierarchical cluster analysis with an explained variance of 61.17% suggests the existence of four large groups distinguished according to the degree of admixture between Amerindians, Europeans, and Africans. Am. J. Hum. Biol., 2008.

Time trends and determinants of completed family size in a rural community from the Basque area of Spain (1800-1969).

The focus of this work is the analysis of changes in completed family size and possible determinants of that size over time, in an attempt to characterize the evolution of reproductive patterns during the demographic transition. With this purpose in mind, time trends are studied in relation to the mean number of live births per family (as an indirect measure of fertility), using family reconstitution techniques to trace the reproductive history of each married woman. The population surveyed is a Spanish rural community called Lanciego, located at the southern end of the province of Alava (Basque Country). A total of 24,510 parish records of baptisms, marriages and burials made between 1800 and 1969 were examined to obtain the demographic data set. For each reconstituted family, the variables included in the study were the number of live births per family or family size (FAMS), year of marriage (YEAR), age at marriage of both partners (AMAN, AWOM), wifes age at the end of marriage (WEND), duration of marriage (MARD), age at first maternity (A1CH), length of reproductive span (REPS) and number of children dying before their first anniversary (MINF). Through a principal component analysis, three factors were found that explained more than 75% of the total variance. Association of variables in factors I and III was particularly useful in characterizing the variability of mean family size in pre-transitional, transitional and post-transitional cohorts. During demographic transition, a decreasing trend is observed in the variables FAMS, REPS and MINF, while variables AWOM, AMAN, WEND and A1CH show a tendency to increase over the 20th century. Results obtained by multiple regression analysis confirm that the best predictors of family size (dependent variable) were REPS and MINF, which between them explained over 85% of the total variation in FAMS (R2 = 0.853). In Lanciego, birth control seems to be present on the evidence of an increase in age at first maternity and a decrease in age at last parturition, indicating that the beginning of the reproductive span is delayed and its end is brought forward. Interaction between family size and infant mortality is discussed in the light of various hypotheses, including replacement of descendants, the so-called biological effect and the theory of r and k selection.

The Andalusian population from Huelva reveals a high diversification of Y-DNA paternal lineages from haplogroup E: Identifying human male movements within the Mediterranean space

Abstract Background: Gene flow among human populations is generally interpreted in terms of complex patterns, with the observed gene frequencies being the consequence of the entire genetic and demographic histories of the population. Aims: This study performs a high-resolution analysis of the Y-chromosome haplogroup E in Western Andalusians (Huelva province). The genetic information presented here provides new insights into migration processes that took place throughout the Mediterranean space and tries to evaluate its impact on the current genetic composition of the most southwestern population of Spain. Subjects and methods: 167 unrelated males were previously typed for the presence/absence of the Y-chromosome Alu polymorphism (YAP). The group of YAP (+) Andalusians was genotyped for 16 Y-SNPs and also characterized for 16 Y-STR loci. Results: The distribution of E-M81 haplogroup, a Berber marker, was found at a frequency of 3% in our sample. The distribution of M81 frequencies in Iberia seems to be not concordant with the regions where Islamic rule was most intense and long-lasting. The study also showed that most of M78 derived allele (6.6%) led to the V13* subhaplogroup. We also found the most basal and rare paragroup M78* and others with V12 and V65 mutations. The lineage defined by M34 mutation, which is quite frequent in Jews, was detected as well. Conclusions: The haplogroup E among Western Andalusians revealed a complex admixture of genetic markers from the Mediterranean space, with interesting signatures of populations from the Middle East and the Balkan Peninsula and a surprisingly low influence by Berber populations compared to other areas of the Iberian Peninsula.

Pneumocystis jiroveci (carinii) pneumonia following a second infusion of infliximab in a patient with ulcerative colitis

To the Editor: The anti–tumor necrosis factor– (TNF ) antibody infliximab is an effective therapy for patients with moderately severe ulcerative colitis who fail to respond to conventional therapy.1 Adverse effects related to infection are a major concern with the use of infliximab. Pneumocystis jiroveci (carinii) pneumonia is an uncommonly reported complication of infliximab-treated patients with inflammatory bowel disease. There have been a few case reports of Pneumocystis pneumonia occurring during infliximab therapy for Crohn’s disease.2–6 This is the first report of Pneumocystis pneumonia complicating therapy of infliximab in a patient with ulcerative colitis. A 45-year-old man with ulcerative colitis was admitted to the hospital in June 2006 because of a moderately severe exacerbation of ulcerative colitis. He had been taking corticosteroids and azathioprine since the initial diagnosis of the disease, which was established elsewhere in 2005. Treatment at the time of admission included azathioprine 100 mg/day, prednisone 16 mg/day, and mesalazine 3 g/day. He received 1 infusion of infliximab (Remicade, ScheringPlough, Madrid, Spain) 5 mg/kg intravenously, followed by a second infusion 15 days later. HIV, HBV, and HCV serologies were negative before infliximab therapy. Tuberculin skin testing was also negative. A positive clinical response was seen after the initial administration. However, 1 week after the second infusion of infliximab, he was admitted to the hospital because of fever of 39°C, fatigue, and headache. The white blood cell count was 3800/mm, the lymphocyte count 1300/mm, hemoglobin 10.7 g/dL, hematocrit 30.3%, serum albumin 2.5 g/dL, and C-reactive protein level 47 mg/L. Physical examination was unrevealing, but the chest X-ray showed a right basal infiltrate consistent with pneumonia. After discontinuation of azathioprine and reduction of the dose of prednisone to 8 mg/ day, intravenous empiric antibiotics was started (imipenem 500 mg every 6 hours, ciprofloxacin 400 mg every 12 hours, and metronidazole 500 mg every 8 hours). He did not improve during the next 48 hours and was admitted to the intensive care unit because of severe respiratory failure, with arterial oxygen saturation 85% despite 3 L/min oxygen therapy. Chest X-ray findings deteriorated (Fig. 1). Treatment with intravenous trimethoprim-salfamethoxazole (1600 mg every 8 hours) was started based on clinical suspicion of opportunistic infection caused by Pneumocystis jiroveci. Bronchoscopy with bronchoalveolar lavage confirmed the presence of P. jiroveci. The CD4 lymphocyte count was 180 cells/mm. Intravenous trimethoprim-salfamethoxazole was given for 2 weeks, followed by oral therapy. Follow-up laboratory tests and chest Xray showed complete resolution. When last seen, in October 2007, he had no complaints, and nothing abnormal could be found on examination or chest radiographs. Given the temporal relationship between infliximab and the onset of symptoms, we suspected that TNF therapy was related to P. jiroveci infection. To our knowledge no previous cases of P. jiroveci pneumonia have been reported associated with the use of infliximab in patients with ulcerative colitis. In agreement with previous reports of Pneumocystis pneumonia complicating therapy of infliximab in patients with Crohn’s disease,2–5 there was concurrent immunosuppression with corticosteroids and/or azathioprine. Bronchoalveolar lavage must be rapidly performed in patients with inflammatory bowel disease presenting with fever, pulmonary infiltrates, lymphopenia, and hypoxemia. Pneumocystis pneumonia remains a serious cause of morbidity and mortality in immunocompromised