Integration of targeted sequencing and pseudo-tetraploid genotyping into clinically assisted decision support for ß-thalassemia invasive prenatal diagnosis.

BACKGROUND: The high prevalence of ß-thalassemia indicates the severe medical burden in Guangxi province in China. Millions of thousands of prenatal women with healthy or thalassemia-carrying fetuses received an unnecessary prenatal diagnosis. We designed a prospective single-center proof-of-concept study to evaluate the utility of a noninvasive prenatal screening method in the stratification of beta-thalassemia patients before invasive procedures. METHODS: Next-generation and optimized pseudo-tetraploid genotyping-based methods were utilized in preceding invasive diagnosis stratification to predict the mater-fetus genotype combinations in cell-free DNA, which is from maternal peripheral blood. Populational linkage disequilibrium information with additional neighboring loci to infer the possible fetal genotype. The concordance of the pseudo-tetraploid genotyping with the gold standard invasive molecular diagnosis was used to evaluate the effectiveness of this method. RESULTS: 127 ß-thalassemia carrier parents were consecutively recruited. The total genotype concordance rate is 95.71%. The Kappa value was 0.8248 for genotype combinations and 0.9118 for individual alleles. CONCLUSION: This study offers a new approach to picking out the health or carrier fetus before invasive procedures. It provides valuable novel insight into patient stratification management on ß-thalassemia prenatal diagnosis.

Design and theoretical analysis of a resonant sensor for liquid density measurement.

In order to increase the accuracy of on-line liquid density measurements, a sensor equipped with a tuning fork as the resonant sensitive component is designed in this paper. It is a quasi-digital sensor with simple structure and high precision. The sensor is based on resonance theory and composed of a sensitive unit and a closed-loop control unit, where the sensitive unit consists of the actuator, the resonant tuning fork and the detector and the closed-loop control unit comprises precondition circuit, digital signal processing and control unit, analog-to-digital converter and digital-to-analog converter. An approximate parameters model of the tuning fork is established and the impact of liquid density, position of the tuning fork, temperature and structural parameters on the natural frequency of the tuning fork are also analyzed. On this basis, a tuning fork liquid density measurement sensor is developed. In addition, experimental testing on the sensor has been carried out on standard calibration facilities under constant 20 °C, and the sensor coefficients are calibrated. The experimental results show that the repeatability error is about 0.03% and the accuracy is about 0.4 kg/m(3). The results also confirm that the method to increase the accuracy of liquid density measurement is feasible.