Anaemia among clinically well under-fives attending a community health centre in Venda, Limpopo Province

Background. Anaemia has been reported to affect 20 - 75% of children in South Africa. The range suggests the effects that geography, health, and socio-economic status can have on the observed prevalence of anaemia within a specific community. Our objective was to investigate the prevalence of anaemia in children aged under 5 presenting for well-child examinations at a community health centre in Thohoyandou, Limpopo Province. Design. A cross-sectional observational study was carried out in June and July 2007. Caregivers participated in a brief interview where demographic, health and nutritional information was collected. A blood sample was collected from each child, and haemoglobin levels were assessed with a point-of-care haemoglobin testing system. Anaemia was defined as having a haemoglobin valu

VariVis: a visualisation toolkit for variation databases

<p>Abstract</p> <p>Background</p> <p>With the completion of the Human Genome Project and recent advancements in mutation detection technologies, the volume of data available on genetic variations has risen considerably. These data are stored in online variation databases and provide important clues to the cause of diseases and potential side effects or resistance to drugs. However, the data presentation techniques employed by most of these databases make them difficult to use and understand.</p> <p>Results</p> <p>Here we present a visualisation toolkit that can be employed by online variation databases to generate graphical models of gene sequence with corresponding variations and their consequences. The VariVis software package can run on any web server capable of executing Perl CGI scripts and can interface with numerous Database Management Systems and "flat-file" data files. VariVis produces two easily understandable graphical depictions of any gene sequence and matches these with variant data. While developed with the goal of improving the utility of human variation databases, the VariVis package can be used in any variation database to enhance utilisation of, and access to, critical information.</p

SMN1 dosage analysis in spinal muscular atrophy from India

BACKGROUND: Spinal muscular atrophy (SMA) represents the second most common fatal autosomal recessive disorder after cystic fibrosis. Due to the high carrier frequency, the burden of this genetic disorder is very heavy in developing countries like India. As there is no cure or effective treatment, genetic counseling becomes very important in disease management. SMN1 dosage analysis results can be utilized for identifying carriers before offering prenatal diagnosis in the context of genetic counseling. METHODS: In the present study we analyzed the carrier status of parents and sibs of proven SMA patients. In addition, SMN1 copy number was determined in suspected SMA patients and parents of children with a clinical diagnosis of SMA. RESULTS: wenty nine DNA samples were analyzed by quantitative PCR to determine the number of SMN1 gene copies present, and 17 of these were found to have one SMN1 gene copy. The parents of confirmed SMA patients were found to be obligate carriers of the disease. Dosage analysis was useful in ruling out clinical suspicion of SMA in four patients. In a family with history of a deceased floppy infant and two abortions, both parents were found to be carriers of SMA and prenatal diagnosis could be offered in future pregnancies. CONCLUSION: SMN1 copy number analysis is an important parameter for identification of couples at risk for having a child affected with SMA and reduces unwarranted prenatal diagnosis for SMA. The dosage analysis is also useful for the counseling of clinically suspected SMA with a negative diagnostic SMA test

A Drastic Reduction in the Life Span of Cystatin C L68Q Carriers Due to Life-Style Changes during the Last Two Centuries

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here, we report, based both on linkage disequilibrium and genealogical evidence, that all known copies of this mutation derive from a common ancestor born roughly 18 generations ago. Intriguingly, the genealogies reveal that obligate L68Q carriers born 1825 to 1900 experienced a drastic reduction in life span, from 65 years to the present-day average. At the same time, a parent-of-origin effect emerged, whereby maternal inheritance of the mutation was associated with a 9 year reduction in life span relative to paternal inheritance. As these trends can be observed in several different extended families, many generations after the mutational event, it seems likely that some environmental factor is responsible, perhaps linked to radical changes in the life-style of Icelanders during this period. A mutation with such radically different phenotypic effects in reaction to normal variation in human life-style not only opens the possibility of preventive strategies for HCCAA, but it may also provide novel insights into the complex relationship between genotype and environment in human disease

Mining phenotypes for gene function prediction

<p>Abstract</p> <p>Background</p> <p>Health and disease of organisms are reflected in their phenotypes. Often, a genetic component to a disease is discovered only after clearly defining its phenotype. In the past years, many technologies to systematically generate phenotypes in a high-throughput manner, such as RNA interference or gene knock-out, have been developed and used to decipher functions for genes. However, there have been relatively few efforts to make use of phenotype data beyond the single genotype-phenotype relationships.</p> <p>Results</p> <p>We present results on a study where we use a large set of phenotype data – in textual form – to predict gene annotation. To this end, we use text clustering to group genes based on their phenotype descriptions. We show that these clusters correlate well with several indicators for biological coherence in gene groups, such as functional annotations from the Gene Ontology (GO) and protein-protein interactions. We exploit these clusters for predicting gene function by carrying over annotations from well-annotated genes to other, less-characterized genes in the same cluster. For a subset of groups selected by applying objective criteria, we can predict GO-term annotations from the biological process sub-ontology with up to 72.6% precision and 16.7% recall, as evaluated by cross-validation. We manually verified some of these clusters and found them to exhibit high biological coherence, e.g. a group containing all available antennal Drosophila odorant receptors despite inconsistent GO-annotations.</p> <p>Conclusion</p> <p>The intrinsic nature of phenotypes to visibly reflect genetic activity underlines their usefulness in inferring new gene functions. Thus, systematically analyzing these data on a large scale offers many possibilities for inferring functional annotation of genes. We show that text clustering can play an important role in this process.</p

Phenylketonuria in Portugal: Genotype-Phenotype Correlations Using Molecular, Biochemical, and Haplotypic Analyses

The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease.info:eu-repo/semantics/publishedVersio

Pre-attentive processing in children with early and continuously-treated PKU. Effects of concurrent Phe level and lifetime dietary control

Sixty-four children, aged 7 to 14 years, with early-treated PKU, were compared with control children on visual evoked potential (VEP) amplitudes and latencies and auditory mismatch negativity (MMN) amplitudes. It was further investigated whether indices of dietary control would be associated with these evoked potentials parameters. There were no significant differences between controls and children with PKU in VEP- and MMN-indices. However, higher lifetime Phe levels were, in varying degree and stronger than concurrent Phe level, related to increased N75 amplitudes, suggesting abnormalities in attention, and longer P110 latencies, indicating a reduction in speed of neural processing, possibly due to deficits in myelination or reduced dopamine levels in brain and retina. Similarly, higher lifetime Phe levels and Index of Dietary Control (IDC) were associated with decreased MMN amplitudes, suggesting a reduced ability to respond to stimulus change and poorer triggering of the frontally mediated attention switch. In summary, the present study in children with PKU investigated bottom-up information processing, i.e., triggered by external events, a fundamental prerequisite for the individual’s responsiveness to the outside world. Results provide evidence that quality of dietary control may affect the optimal development of these pre-attentive processes, and suggest the existence of windows of vulnerability to Phe exposure