Common ABCA4 mutations in South Africans: frequencies, pathogenicity and genotype-phenotype correlations

Stargardt disease (STGD), a juvenile-onset form of macular dystrophy resulting in a severe reduction of central vision, may be inherited in either an autosomal recessive or autosomal dominant manner. To date the only gene found to be involved with the autosomal recessive form is ABCA4. Mutations in this gene are associated not only with STGD, but with other autosomal recessive retinal diseases. Due to the numerous mutations detected in ABCA4 and their associated phenotypic heterogeneity, a genotype-phenotype model has been proposed based on the amount of ABCA4 protein activity. Research in the Division of Human Genetics at the University of Cape Town (UCT) has suggested possible ABCA4 founder mutations underlying STGD in the South African Caucasian Afrikaner population and has identified seven (C1490Y, R602W, IVS38-10T>C, L2027F, V256V, G863A, and R152X) common mutations. In a cohort of patients affected with an ABCA4-associated retinopathy (AAR) a total of 36% were identified as having various bi-allelic combinations of the seven mutations.In the current study, SNaPshot PCR, allele-specific PCR (AS-PCR) and denaturing high performance liquid chromatography (dHPLC) analysis were used to screen for the seven mutations in a patient cohort and a control cohort. A high detection rate of bi-allelic disease-causing mutations in total of 28/72 patients (i.e. 38.89% were fully characterised) confirmed the designed assay to be a viable screening tool, which could be employed in a diagnostic setting. The detection of 12 heterozygotes in the Caucasian control samples (n = 269; 169 of which were specifically Afrikaner) resulted in an estimated background frequency of 4.46 per 100 individuals. This could be used by counsellors to discuss carrier risks with patients and their family members. Bioinformatic tools (PolyPhen, SIFT, PMUT, PANTHER PSEC, ESEfinder, and the BDGP Splice Site Prediction programme) revealed the predicted pathogenicity of the seven mutations to be as follows (in order of decreasing pathogenicity): C1490Y, R602W, V256V, R152X, G863A, L2027F, and IVS38-10T>C. Statistical analysis (using the Kruskal-Wallis test and the Wilcoxon Rank Sum test) showed no significant12effect of mutation combination on phenotype (i.e. AOO/severity as a measure of clinical outcome).To improve the understanding of the genotype-phenotype correlation a larger cohort of South African STGD patients with the same common mutations in various combinations and the availability of sufficient clinical data, is required. Further investigations into the genotype-phenotype correlation, combined with the information on the pathogenicity of the mutations, could result in increased understanding regarding the impact of each mutation, thus enhancing the clinical utility of identifying ABCA4 mutations

Full dynamic resolution low lower DA-Converters for flat panel displays

It has been shown that stepwise charging can reduce the power dissipated in the source drivers of a flat panel display. However the solution presented only provided a dynamic resolution of 3 bits which is not sufficient for obtaining a full color resolution display. In this work a further development of the basic idea is presented. The stepwise charging is increased to 4 bits and supplemented by a current source to provide an output signal which represents an 8 bit value with sufficient accuracy. Within this work the application is an AM-OLED flat panel display, but the concept can easily be applied to other display technologies like TFT-LCD as well

Near-field MIMO communication links

A procedure to achieve near-field multiple input multiple output (MIMO) communication with equally strong channels is demonstrated in this paper. This has applications in near-field wireless communications, such as Chip-to-Chip (C2C) communication or wireless links between printed circuit boards. Designing the architecture of these wireless C2C networks is, however, based on standard engineering design tools. To attain this goal, a network optimization procedure is proposed, which introduces decoupling and matching networks. As a demonstration, this optimization procedure is applied to a 2-by-2 MIMO with dipole antennas. The potential benefits and design trade-offs are discussed for implementation of wireless radio-frequency interconnects in chip-to-chip or device-to-device communication such as in an Internet-of-Things scenario

Psychosis and relapse in bipolar disorder are related to GRM3, DAOA, and GRIN2B genotype

Objective:  Key Words: Manic-Depressive Psychosis; Glutamate; GRIN2B receptor; mGluR3; G72 protein; HumanDysfunction in glutamate signalling is thought to play a role in the pathophysiology of bipolar disorder (BD). There is evidence of associations between single nucleotide polymorphisms (SNPs) in GRM3, GRIN2B, and DAOA genes and the diagnosis of BD. In this pilot study, we investigated the frequency of SNP variants in these 3 genes within South African population groups, and assessed interactions between genes and phenotypes of BD disease severity. Method: Multiplex SNaPshotTM PCR was used to genotype 191 case and 188 control samples. Cases comprised of 191 individuals in a South African cohort of mixed ancestry and Caucasians, with BD Type 1. Phenotypes of BD disease severity were: age of onset, number of illness episodes, number of hospitalisations for depression or mania and history of psychotic symptoms. Results: There were no significant difference in SNP allele frequencies between cases and controls. In the case-only analysis, the GRM3 rs6465084 heterozygote was associated with a 4-fold increased risk of lifetime history of psychotic symptoms, and the specific variants within the gene pair, DAOA and GRIN2B, had a significant interaction with the number of hospitalisations for mania, with lowest admission rates associated with both pairs of ancestral alleles. Conclusion: In BD, variations in glutamatergic genes may influence phenotypes related to the severity of illness. Speculatively, newly derived genes associated with various evolutionary advantages, may also increase the risk for more severe BD. These preliminary findings deserve validation in a larger cohort

Analysis of a near field MIMO wireless channel using 5.6 GHz dipole antennas

Understanding the impact of interference upon the performance of a multiple input multiple output (MIMO) based device is of paramount importance in ensuring a design is both resilient and robust. In this work the effect of element-element interference in the creation of multiple channels of a wireless link approaching the near-field regime is studied. The elements of the 2-antenna transmit- and receive-arrays are chosen to be identical folded dipole antennas operating at 5.6 GHz. We find that two equally strong channels can be created even if the antennas interact at sub-wavelength distances, thus confirming previous theoretical predictions

Analysis of a near field MIMO wireless channel using 5.6 GHz dipole antennas

Understanding the impact of interference upon the performance of a multiple input multiple output (MIMO) based device is of paramount importance in ensuring a design is both resilient and robust. In this work the effect of element-element interference in the creation of multiple channels of a wireless link approaching the near-field regime is studied. The elements of the 2-antenna transmit- and receive-arrays are chosen to be identical folded dipole antennas operating at 5.6 GHz. We find that two equally strong channels can be created even if the antennas interact at sub-wavelength distances, thus confirming previous theoretical predictions

Analysis of a near field MIMO wireless channel using 5.6 GHz dipole antennas

Understanding the impact of interference upon the performance of a multiple input multiple output (MIMO) based device is of paramount importance in ensuring a design is both resilient and robust. In this work the effect of element-element interference in the creation of multiple channels of a wireless link approaching the near-field regime is studied. The elements of the 2-antenna transmit- and receive-arrays are chosen to be identical folded dipole antennas operating at 5.6 GHz. We find that two equally strong channels can be created even if the antennas interact at sub-wavelength distances, thus confirming previous theoretical predictions

Thermoelectric effect in very thin film Pt∕Au thermocouples

The thickness dependence of the thermoelectric power of Pt films of variable thickness on a reference Au film has been determined for the case when the Pt film thickness, t, is not large compared to the charge carrier mean free path, {ell}, that is, t/{ell}. Pt film thicknesses down to 2.2 nm were investigated. We find that {Delta}S{sub F} = S{sub B}-S{sub F} (where S{sub B} and S{sub F} are the thermopowers of the Pt bulk and film, respectively) does not vary linearly as 1/t as is the case for thin film thermocouples when the film thickness is large compared to the charge carrier mean free path