Investigation of G72 (DAOA) expression in the human brain

<p>Abstract</p> <p>Background</p> <p>Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO), supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions.</p> <p>Methods</p> <p>The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth <it>in silico </it>analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability.</p> <p>Results</p> <p>Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis) human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala), spinal cord or testis. A detailed <it>in silico </it>analysis provides several lines of evidence that support the apparent low or absent expression of G72.</p> <p>Conclusion</p> <p>Our results suggest that native G72 protein is not normally present in the tissues that we analysed in this study. We also conclude that the lack of demonstrable G72 expression in relevant brain regions does not support a role for G72 in modulation of DAO activity and the pathology of schizophrenia via a DAO-mediated mechanism. <it>In silico </it>analysis suggests that G72 is not robustly expressed and that the transcript is potentially labile. Further studies are required to understand the significance of the G72/30 locus to schizophrenia.</p

Comparative and evolutionary genomics and proteomics Multi-SNP ANALYSIS OF CCR5-CCR2 GENES IN ETHIOPIAN JEWS: MICRO-EVOLUTION AND HIV-RESISTANCE IMPLICATIONS

SUMMARY Motivation: This is the first report concerning CR5 SNPs in the Ethiopian Jewish population. CCR5 and CCR2 genes have been implicated in HIV disease progression, resistance or non-progressive infection. To determine the influence of host genetics on HIV infection, we examined 29 HIV-seronegative individuals of Ethiopian descent for polymorphisms in the CCR5-CCR2 gene region and compared the results with those of 13 exposed but uninfected individuals. Multi-SNP analysis was used for sample comparisons and for population relationship estimates. Results: Using multi-SNP analysis, no significant differences in the genotypes frequencies between the studied groups was found (

Morpho-Physiological Features of Human Populations in the Context of Climatic – Geographical Conditions

This paper is based on the data obtained in the course of population studies conducted in 33 geographical regions of the former USSR territory by the faculty of the Anuchin Research Institute and Museum of Anthropology, Lomonosov Moscow State University, between 1961 and 1991. The data resulting from study of 4386 male and 4626 female subjects aged 17 to 99 include head and body morphology, bone mineral density, blood oxygen saturation and blood biochemistry. We aimed at studying the link between the traits of a population and the climatic conditions of the area inhabited by this population. Individual characteristics of the subjects were normalized by age and sex, and factor analysis was used to reduce the number of cross-correlating features. As a result, several integral characteristics (factors) were identified: five body morphology-related factors, two headmorphology-related factors, one bone mineral density-related factor, one blood oxygen saturation-related factor and three blood biochemistry-related factors. These factors explained 79.3%, 78.38%, 63.51%, 74.4% and 66.77% of the trait groups’ variability, respectively. The correlation analysis between these factors and climatic indicators demonstrated that chest dimensions were the least tolerant to the climatic conditions among the morphological characteristics studied. Hemoglobin-protein ratios, as well as the factor that includes total cholesterol, were the most climate-dependent among the biochemical parameters. As far as our data show, blood serum oxygen saturation – the key factor determining the performance of the cardiovascular and respiratory systems – is also climate-dependent

Discrete optimization for some TSP-like genome mapping problems

Several problems in modern genome mapping analysis belong to the field of discrete optimization on a set of all possible orders. In this paper we propose formulations, mathematical models and algorithms for genetic/genomic mapping problem, that can be formulated in TSP-like terms. These include: ordering of marker loci (or genes) in multilocus genetic mapping (MGM), multilocus consensus mapping (MCGM), and physical mapping problem (PMP). All these problems are considered as computationally challenging because of noisy marker scores, large-size data sets, specific constraints on certain classes of orders, and other complications. The presence of specific constrains on ordering of some elements in these problems does not allow applying effectively the well-known powerful discrete optimization algorithms like Cutting-plane, Genetic algorithm with EAX crossover and famous Lin-Kernighan. In the paper we demonstrate that developed by us Guided Evolution Strategy algorithms successfully solves this class of discrete constrained optimization problems. The efficiency of the proposed algorithm is demonstrated on standard TSP problems and on three genetic/genomic problems with up to 2,500 points

Novel ANKH amino terminus mutation (pro5ser) associated with early-onset calcium pyrophosphate disease with associated phosphaturia

This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband’s DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband’s father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband’s father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband’s father