CD209 in inflammatory bowel disease: a case-control study in the Spanish population

BACKGROUND The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The CD209 gene is located in a region linked previously to IBD and a CD209 functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this CD209 variant in IBD susceptibility. METHODS We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the CD209 single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using chi2 tests. RESULTS No association between CD209 and UC or CD was observed initially. However, stratification of UC patients by HLA-DR3 status, a strong protective allele, showed that carriage of the CD209_G allele could increase susceptibility in the subgroup of HLA-DR3-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04-3.02, vs. controls). CONCLUSION A functional variant in the CD209 gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in HLA-DR3-positive individuals but further studies are necessary.

'Greek' and 'Roman' in Latin Medical Texts. Studies in Cultural Change and Exchange in Ancient Medicine : [Proceedings of the 10th International Conference "Ancient Latin Medical Texts", Lausanne, 2010, November 3rd-6th November]

Latin medical texts transmit medical theories and practices that originated mainly in Greece. This interaction took place through juxtaposition, assimilation and transformation of ideas. 'Greek' and 'Roman' in Latin Medical Texts studies the ways in which this cultural interaction influenced the development of the medical profession and the growth of knowledge of human and animal bodies, and especially how it provided the foundations for innovations in the areas of anatomy, pathology and pharmacology, from the earliest Latin medical texts until well into the medieval world.

Association study of genetic variants of pro-inflammatory chemokine and cytokine genes in systemic lupus erythematosus

BACKGROUND. Several lines of evidence suggest that chemokines and cytokines play an important role in the inflammatory development and progression of systemic lupus erythematosus. The aim of this study was to evaluate the relevance of functional genetic variations of RANTES, IL-8, IL-1alpha, and MCP-1 for systemic lupus erythematosus. METHODS. The study was conducted on 500 SLE patients and 481 ethnically matched healthy controls. Genotyping of polymorphisms in the RANTES, IL-8, IL-1alpha, and MCP-1 genes were performed using a real-time polymerase chain reaction (PCR) system with pre-developed TaqMan allelic discrimination assay. RESULTS. No significant differences between SLE patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the RANTES, IL-8, IL-1alpha, and MCP-1 polymorphisms. In addition, no evidence for association with clinical sub-features of SLE was found. CONCLUSION. These results suggest that the tested functional variation of RANTES, IL-8, IL-1alpha, and MCP-1 genes do not confer a relevant role in the susceptibility or severity of SLE in the Spanish population.

On the use of principal components in contemporany population genetics: a case study

In human Population Genetics, routine applications of principal component techniques are oftenrequired. Population biologists make widespread use of certain discrete classifications of humansamples into haplotypes, the monophyletic units of phylogenetic trees constructed from severalsingle nucleotide bimorphisms hierarchically ordered. Compositional frequencies of the haplotypesare recorded within the different samples. Principal component techniques are then required as adimension-reducing strategy to bring the dimension of the problem to a manageable level, say two,to allow for graphical analysis.Population biologists at large are not aware of the special features of compositional data and normally make use of the crude covariance of compositional relative frequencies to construct principalcomponents. In this short note we present our experience with using traditional linear principalcomponents or compositional principal components based on logratios, with reference to a specificdataset

CA88, a nuclear repetitive DNA sequence identified in Schistosoma mansoni, aids in the genotyping of nine Schistosoma species of medical and veterinary importance

CA88 is the first long nuclear repetitive DNA sequence identified in the blood fluke, Schistosoma mansoni. The assembled S. mansoni sequence, which contains the CA88 repeat, has 8,887 nucleotides and at least three repeat units of approximately 360 bp. In addition, CA88 also possesses an internal CA microsatellite, identified as SmBr18. Both PCR and BLAST analysis have been used to analyse and confirm the CA88 sequence in other S. mansoni sequences in the public database. PCR-acquired nuclear repetitive DNA sequence profiles from nine Schistosoma species were used to classify this organism into four genotypes. Included among the nine species analysed were five sequences of both African and Asian lineages that are known to infect humans. Within these genotypes, three of them refer to recognised species groups. A panel of four microsatellite loci, including SmBr18 and three previously published loci, has been used to characterise the nine Schistosoma species. Each species has been identified and classified based on its CA88 DNA fingerprint profile. Furthermore, microsatellite sequences and intra-specific variation have also been observed within the nine Schistosoma species sequences. Taken together, these results support the use of these markers in studying the population dynamics of Schistosoma isolates from endemic areas and also provide new methods for investigating the relationships between different populations of parasites. In addition, these data also indicate that Schistosoma magrebowiei is not a sister taxon to Schistosoma mattheei, prompting a new designation to a basal clade.

Turner syndrome: evaluation of prenatal diagnosis in 19 European registries.

This study evaluated the prenatal diagnosis of Turner syndrome by ultrasound examination in an unselected population from all over Europe. Data from 19 congenital malformation registries from 11 European countries were analyzed. Turner syndrome was diagnosed in 125 cases (7.2%) in a total of 1,738 chromosome abnormalities. Sixty-seven percent of cases were detected prenatally by ultrasound examination due to the presence of congenital defects. The most frequent anomalies were cystic hygroma (59.5%) and hydrops fetalis (19%). The most frequent karyotype was 45,X (81.6%) followed by different types of mosaicism (16.8%). Significant differences in congenital defects (P = 0.0003) were observed between 45,X karyotypes and 45,X mosaicism cases. Prenatal counseling for 45,X mosaicism should take into account the expectation of a milder phenotype. In 78.6% of cases diagnosed by ultrasound examination due to congenital anomalies, the pregnancy was terminated. Prenatal detection of Turner syndrome by ultrasound examination was high in this unselected population.

Catastrophic medical expenditure risk

Medical expenditure risk can pose a major threat to living standards. We derive decomposable measures of catastrophic medical expenditure risk from reference-dependent utility with loss aversion. We propose a quantile regression based method of estimating risk exposure from cross-section data containing information on the means of financing health payments. We estimate medical expenditure risk in seven Asian countries and find it is highest in Laos and China, and is lowest in Malaysia. Exposure to risk is generally higher for households that have less recourse to self-insurance, lower incomes, wealth and education, and suffer from chronic illness.

Estudio de la influencia de la nutrición y genética maternas sobre la programación del desarrollo del tejido adiposo fetal (Estudio PREOBE).

BACKGROUND. Maternal genetics and feeding before and during pregnancy, different maternal metabolic pathologies, as well as nutrient intakes of newborns in their first months of life may be involved in the obesity aetiology and its long-term consequences. The possible role of these and others factors, the mechanisms and the effects on the metabolism, and the development of this disease need further research. OBJECTIVE. To acquire more knowledge about foetal adipose tissue development and the influence of genetic, dietetic and environmental factors on the risk to suffer from obesity. METHODOLOGY. Four study groups have been established with 30 pregnant women in each one: 1) control group; 2) mothers with glucose intolerance/gestational diabetes; 3) women with low weight gain during pregnancy, and 4) women with overweight/obesity at the beginning of the pregnancy. The magnitudes to be studied are: 1) dietary intake; 2) life-style habits; 3) physical activity; 4) anthropometry and body composition; 5) haematological study; 6) biochemical study (lipid and metabolic biomarkers); 7) immune function profile related to nutritional status; 8) psychological profile; 9) genetic biomarkers, and 10) microbiological markers; all of them in relation to the development of the foetal adipose tissue in the first stages of life and the risk of suffering from obesity in the future. CONCLUSION. This project, coordinated by the Department of Paediatrics of the School of Medicine in the University of Granada, and with the collaboration of well-known and expert research groups, tries to contribute to the knowledge about the obesity aetiology in infancy and its subsequent development in later periods of life.

Medical image registration based on random line sampling

One of the key aspects in 3D-image registration is the computation of the joint intensity histogram. We propose a new approach to compute this histogram using uniformly distributed random lines to sample stochastically the overlapping volume between two 3D-images. The intensity values are captured from the lines at evenly spaced positions, taking an initial random offset different for each line. This method provides us with an accurate, robust and fast mutual information-based registration. The interpolation effects are drastically reduced, due to the stochastic nature of the line generation, and the alignment process is also accelerated. The results obtained show a better performance of the introduced method than the classic computation of the joint histogram

A novel study of copy number variations in Hirschsprung disease using the multiple ligation-dependent probe amplification (MLPA) technique.

BACKGROUND Hirschsprung disease (HSCR) is a congenital malformation of the hindgut produced by a disruption in neural crest cell migration during embryonic development. HSCR has a complex genetic etiology and mutations in several genes, mainly the RET proto-oncogene, have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis. METHODS In this study we have aimed to analyze the presence of CNVs in some HSCR genes (RET, EDN3, GDNF and ZFHX1B) using the Multiple Ligation-dependent Probe Amplification (MLPA) approach. RESULTS Two alterations in the MLPA profiles of RET and EDN3 were detected, but a detailed inspection showed that the decrease in the corresponding dosages were due to point mutations affecting the hybridization probes regions. CONCLUSION Our results indicate that CNVs of the gene coding regions analyzed here are not a common molecular cause of Hirschsprung disease. However, further studies are required to determine the presence of CNVs affecting non-coding regulatory regions, as well as other candidate genes.