• Journal of Genetic Medicine
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• v.12 no.2
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• pp.72-78
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• 2015

Recently, noninvasive prenatal test (NIPT) has been adopted as a primary screening tool for fetal chromosomal aneuploidy. The principle of NIPT lies in isolating the fetal fraction of cell-free DNA in maternal plasma and analyzing it with bioinformatic tools to measure the amount of gene from the target chromosome, such as chromosomes 21, 18, and 13. NIPT will contribute to decreasing the need for unnecessary invasive procedures, including amniocentesis and chorionic villi sampling, for confirming fetal aneuploidy because of its higher positive predictive value than that of the conventional prenatal screening method. However, its greater cost than that of the current antenatal screening protocol may be an obstacle to the adoption of this innovative technique in clinical practice. Digital polymerase chain reaction (dPCR) is a novel approach for detecting and quantifying nucleic acid. dPCR provides real-time diagnostic advantages with higher sensitivity, accuracy, and absolute quantification than conventional quantitative PCR. Since the groundbreaking discovery that fetal cell-free nucleic acid exists in maternal plasma was reported, dPCR has been used for the quantification of fetal DNA and for screening for fetal aneuploidy. It has been suggested that dPCR will decrease the cost by targeting specific sequences in the target chromosome, and dPCR-based noninvasive testing will facilitate progress toward the implementation of a noninvasive approach for screening for trisomy 21, 18, and 13. In this review, we highlight the principle of dPCR and discuss its future implications in clinical practice.

• Korean Journal of Environmental Biology
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• v.26 no.3
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• pp.264-269
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• 2008

This study was intended to test the feasibility of genetic analysis of wintering population of geese using their feces samples. This noninvasive approach is quite significant and effective because we do not need to capture or harm geese to obtain the samples. We collected the feces from two different populations of wintering geese in Korea in 2007. Finally thirty two feces were analyzed through a molecular genetic method. As a result, 14 haplotypes were identified and classified into two groups, white-fronted geese (Anser albifrons) and bean geese (Anser fabalis). We established the method to make molecular genetic experiment more efficient using the feces. This study has a significance as the first genetic result on wintering population of geese in Korea using noninvasive sampling method.

• Journal of Genetic Medicine
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• v.11 no.2
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• pp.43-48
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• 2014

Chorionic villus sampling has gained importance as a tool for early cytogenetic diagnosis with a shift toward first trimester screening. First trimester screening using nuchal translucency and biomarkers is effective for screening. Chorionic villus sampling generally is performed at 10-12 weeks by either the transcervical or transabdominal approach. There are two methods of analysis; the direct method and the culture method. While the direct method may prevent maternal cell contamination, the culture method may be more representative of the true fetal karyotype. There is a concern for mosaicism which occurs in approximately 1% of cases, and mosaic results require genetic counseling and follow-up amniocentesis or fetal blood sampling. In terms of complications, procedure-related pregnancy loss rates may be the same as those for amniocentesis when undertaken in experienced centers. When the procedure is performed after 9 weeks gestation, the risk of limb reduction is not greater than the risk in the general population. At present, chorionic villus sampling is the gold standard method for early fetal karyotyping; however, we anticipate that improvements in noninvasive prenatal testing methods, such as cell free fetal DNA testing, will reduce the need for invasive procedures in the near future.

• Journal of Gastric Cancer
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• v.22 no.4
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• pp.306-318
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• 2022

Gastric cancer (GC) is associated with high morbidity and mortality rates. Thus, early diagnosis is important to improve disease prognosis. Endoscopic assessment represents the most reliable imaging method for GC diagnosis; however, it is semi-invasive and costly and heavily depends on the skills of the endoscopist, which limit its clinical applicability. Therefore, the search for new sensitive biomarkers for the early detection of GC using noninvasive sampling collection methods has attracted much attention among scientists. Urine is considered an ideal biofluid, as it is readily accessible, less complex, and relatively stable than plasma and serum. Over the years, substantial progress has been made in screening for potential urinary biomarkers for GC. This review explores the possible applications and limitations of urinary biomarkers in GC detection and diagnosis.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.11-15
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• 2020

Purpose: The objective of this study was to analyze the results of several noninvasive prenatal tests (NIPTs) from a single center and confirm their efficacy and reliability. In addition, we aimed to confirm the changes in the number of invasive tests performed after introducing NIPT. Materials and Methods: NIPT data from a large single center from March 2014 to November 2018 were analyzed. Karyotyping was confirmed based on chorionic villus sampling, amniocentesis, or postnatal cord/peripheral blood sampling. Data on maternal age, gestational age, fetal fraction, and ultrasonographic results were analyzed. As the secondary outcome, the number of amniocentesis cases before and after the introduction of NIPT was compared. Results: Overall, 1,591 single pregnancy cases that underwent NIPT were enrolled. The mean maternal age was 36.05 (22-45) years. The average gestational age and fetal fraction were 12⁺¹ (9⁺³ to 27⁺¹) weeks and 10.95% (3.6% to 31.3%), respectively. A total of 1,544 cases (97.0%) were reported to have negative NIPT results and 40 (2.5%) had positive NIPT results. The sensitivity and specificity of the overall abnormalities in NIPT were 96.29% and 99.36%, respectively. The positive predictive value (PPV) and negative predictive value were 72.22% and 99.93% respectively. The mean number of amniocentesis cases were 21.7 per month (21.7±3.9), which significantly decreased from 31.5 per month (31.5±4.8) before conducting NIPT as a screening test. Conclusion: NIPT is currently a useful, powerful, and safe screening test. In particular, trisomy 21 is highly specific due to its high PPV. NIPT can reduce the potential risks of procedure-related miscarriages during invasive testing.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.100-108
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• 2015

Purpose: Conventional methods for the prenatal detection of fetal RhD status involve invasive procedures such as fetal blood sampling and amniocentesis. The identification of cell-free fetal DNA (cffDNA) in maternal plasma creates the possibility of determining fetal RhD status by analyzing maternal plasma DNA. However, some technical problems still exist, especially the lack of a positive control marker for the presence of fetal DNA. Therefore, we assessed the feasibility and accuracy of fetal RHD genotyping incorporating the RASSF1A epigenetic fetal DNA marker from cffDNA in the maternal plasma of RhD-negative pregnant women in Korea. Materials and Methods: We analyzed maternal plasma from 41 pregnant women identified as RhD-negative by serological testing. Multiplex real-time PCR was performed by amplifying RHD exons 5 and 7 and the SRY gene, with RASSF1A being used as a gender-independent fetal epigenetic marker. The results were compared with those obtained by postnatal serological analysis of cord blood and gender identification. Results: Among the 41 fetuses, 37 were RhD-positive and 4 were RhD-negative according to the serological analysis of cord blood. There was 100% concordance between fetal RHD genotyping and serological cord blood results. Detection of the RASSF1A gene verified the presence of cffDNA, and the fetal SRY status was correctly detected in all 41 cases. Conclusion: Noninvasive fetal RHD genotyping with cffDNA incorporating RASSF1A is a feasible, reliable, and accurate method of determining fetal RhD status. It is an alternative to amniocentesis for the management of RhD-negative women and reduces the need for unnecessary RhIG prophylaxis.

• Journal of Genetic Medicine
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• v.8 no.1
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• pp.1-16
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• 2011

Owing to the risk of fetal loss associated with prenatal diagnostic procedures (amniocentesis, chorionic villus sampling), noninvasive prenatal diagnosis (NIPD) is ultimate goal of prenatal diagnosis. The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma in 1997 has opened up new probabilities for NIPD by Dr. Lo et al. The last decade has seen great development in NIPD. Fetal sex and fetal RhD status determination by cffDNA analysis is already in clinical use in certain countries. For routine use, this test is limited by the amount of cell-free maternal DNA in blood sample, the lack of universal fetal markers, and appropriate reference materials. To improve the accuracy of detection of fetal specific sequences in maternal plasma, internal positive controls to confirm to presence of fetal DNA should be analyzed. We have developed strategies for noninvasive determination of fetal gender, and fetal RhD genotyping using cffDNA in maternal plasma, using real-time quantitative polymerase chain reaction (RT-PCR) including RASSF1A epigenetic fetal DNA marker (gender-independent) as internal positive controls, which is to be first successful study of this kind in Korea. In our study, accurate detection of fetal gender through gestational age, and fetal RhD genotyping in RhD-negative pregnant women was achieved. In this assay, we show that the assay is sensitive, easy, fast, and reliable. These developments improve the reliability of the applications of circulating fetal DNA when used in clinical practice to manage sex-linked disorders (e.g., hemophilia, Duchenne muscular dystrophy), congenital adrenal hyperplasia (CAH), RhD incompatibility, and the other noninvasive pregnant diagnostic tests on the coming soon. The study was the first successful case in Korea using cffDNA in maternal plasma, which has created a new avenue for clinical applications of NIPD.

• Child Health Nursing Research
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• v.15 no.3
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• pp.299-305
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• 2009

Purpose: Multiple studies have documented that high resting levels of cardiac vagal tone suggest higher levels of self-regulation. The aim of this study was to evaluate cardiac vagal tone as an indicator of autonomic nervous function in healthy newborn and premature infants. Methods: This study was conducted using a descriptive comparison design and a convenience sampling strategy. The participants were 72 healthy and 62 premature infants delivered in a university hospital. Continuous heart rate data recordings from the infant's ECG were analyzed and Mxedit software was used to calculate mean heart period and an index of cardiac vagal tone. Results: The healthy infants had significantly higher cardiac vagal tone than the premature infants, when the influence of gestational age was removed using analysis of covariance. However, there were no significant differences in heart rate and heart period between the two groups when the influence of gestational age was removed using analysis of covariance. Conclusion: The results of this study show that cardiac vagal tone may be used as an index for determining infant's autonomic nervous function. Nursing staff in pediatric departments can use cardiac vagal tone with ease, as this index can be calculated in a noninvasive method from the ECG.

• Current Optics and Photonics
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• v.4 no.4
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• pp.368-372
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• 2020

We report the terahertz time-domain spectroscopy (THz-TDS) of transdermal drug delivery in human skin. The time evolution of transdermal nicotine delivery in nicotine patches was assessed by detecting the transmission coefficient of sub-picosecond THz pulses and using a semi-analytic model based on the single-layer effective medium approximation. Using commercial nicotine patches (Nicoderm CQ^®, 7 mg/24 h), THz transmission coefficients were measured to quantitatively analyze the cumulative amounts of nicotine released from the patches in the absence of their detailed specifications, including multilayer structures and optical properties at THz frequencies. The results agreed well with measurements by conventional in vitro and in vivo methods, using a diffusion cell with high-performance liquid chromatography and blood sampling respectively. Our study revealed the ability of the THz-TDS method to be an effective alternative to existing methods for noninvasive and label-free assessments of transdermal drug delivery, showing its high promise for biomedical, pharmaceutical, and cosmetic applications.

• Journal of Genetic Medicine
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• v.17 no.2
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• pp.68-72
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• 2020

Purpose: Trisomy 21, the cause of Down syndrome (DS) with various medical problems, is the most common aneuploidy during the fetal period. For diagnosis, a non-invasive screening test using maternal blood, which cannot be confirmed and invasive confirmation test with a risk of miscarriage, may be performed. The trophoblast retrieval and isolation of the cervix (TRIC) have been proposed by some researchers as an alternative to overcome the limitations of current tests. We experimented using TRIC to identify the possibility of trisomy 21 for the first time in Asia. Materials and Methods: Three cases of DS were analyzed confirmed by invasive tests (chorionic villus sampling, amniocentesis). All samples of trophoblasts immediately were immersed in phosphate-buffered saline and processed with formalin for fixation. The trophoblasts were isolated using an anti-human leukocyte antigen-G antibody coupled to magnetic nanoparticles. β-human chorionic gonadotropin (hCG)-expressing cells were considered as trophoblast cells, and the detection rate calculated. DS was confirmed by fluorescence in situ hybridization (FISH). Results: The mean trophoblast detection rate using β-hCG was 78.1%, and the detection rate using FISH was 22.2%. In all cases, the trisomy of chromosome 21 was identified. Conclusion: Trophoblast can be obtained from the five weeks of gestation and has a high detection rate, so it is noted that it can replace the current prenatal genetic test. To realize the clinical application as a prenatal genetic test, we will need additional efforts to identify trisomy 21 as well as other chromosomal abnormalities in future large-scale studies.