Direct-to-consumer (DTC) genetic testing is a controversial issue although Korean Government is considering to expand DTC genetic testing. Preventing the exaggeration and abusing of DTC genetic testing is an important task considering the early history of DTC genetic testing in Korea. And the DTC genetic testing performance or method has been rarely reported to the scientific and/or medical community and reliability of DTC genetic testing needs to be assessed. Law enforcement needs to improve these issues. Also principle of transparency needs to be applied.
Genetic Testing ; Korea ; Law Enforcement ; Methods

Essential hypertension (EH) is a complex multifactorial disorder with genetic and environmental factors contributing to its prevalence. The genetic features have been revealed from the significant familial aggregation and the consistency among twins. Therefore, identification of EH susceptibility genes will be helpful to understand the pathophysiology of the disease, identify populations with potential risks of developing the disease, and select antihypertensive drugs. The present article introduces the search strategies of EH susceptibility genes and some genetic variants related to EH; meanwhile, it tries to analyze the difficulties and the role for samples in identifying susceptibility genes to EH.
Genetic Predisposition to Disease ; genetics ; Genetic Testing ; methods ; Genetic Variation ; Humans ; Hypertension ; genetics ; Polymorphism, Genetic ; Research Design

OBJECTIVE: To assess the value of preimplantation genetic test (PGT) based on next generation sequencing (NGS) for achieving pregnancy for 71 couples with one partner carrying a reciprocal or Robertsonian translocation. METHODS: Following blastocyst biopsy, whole genome of single cell was amplified, and PGT was performed by NGS. The subjects included 60 couples with one partner carrying a reciprocal translocation and 11 with one partner carrying a Robertsonian translocation. The results of PGT, implantation and prenatal diagnosis for all of the couples were analyzed. RESULTS: In total 301 embryos were obtained for the 71 couples through 92 ovulation cycles, 287 (95.3%) of which were successfully diagnosed by NGS. Eighty-five euploidy embryos were identified for the reciprocal translocation carrier group. In 18 cycles, no euploid embryo was obtained. Cancellation rate for the cycles was 19.5%. For reciprocal translocation carrier group and Robertsonian translocation carrier group, the rates for implantation, early abortion, and clinical pregnancy were 89.3% (42/47), 25.5% (12/47), 63.8% (30/47), and 88.8% (8/9), 22.2% (2/9), and 66.6% (6/9), respectively. The result of prenatal diagnosis was consistent with the that of PGT. CONCLUSION PGT based on NGS can effectively identify euploid embryos and reduce recurrent abortions and termination of pregnancies, achieving a satisfactory rate for clinical pregnancy.
Female ; Fertilization in Vitro ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Pregnancy ; Preimplantation Diagnosis ; methods ; Translocation, Genetic

OBJECTIVETo investigate the efficiency of multi-round fluorescence in situ hybridization (FISH) and its influencing factors in preimplantation genetic diagnosis (PGD).

METHODSA total of 48 couples accepted PGD because of various reasons: 24 with Robertsonian translocations, 16 with reciprocal translocations, 2 with pericentric inversions, one with advanced maternal age who had a previous liveborn of Down syndrome, 3 suffered from sex chromosome abnormalities and 2 repeated spontaneous miscarriages. After 72 retrieval cycles, 432 cleavage stage embryos with more than six cells were biopsied on day three. Only intact nuclei (396) were hybridized in order to verify the chromosomal status of the individual embryos. If previous FISH has failed to give conclusive results while the nuclei remained undamaged, the nuclei were hybridized once again. A total of 870 times of hybridization were conducted to 396 nuclei. Signal identification rates of each round as well as the influence of different probes to the hybridization efficiency were compared. Factors leading to inconclusive FISH results were analyzed as well.

RESULTSFive hundred and thirty five out of 870 hybridizations gave identifiable signals (61.5%). The second and third round FISH showed the best signals with an identification rate of 71.8% and 77.4%, respectively, which were significantly higher than those of the first round (52.8%, P < 0.01), the fourth round (55.8%, P < 0.05, P < 0.01), the fifth round (54.5%, P < 0.05) and the sixth round (27.3%, P < 0.01). The identification rate of centromere specific probe signals (CEP group) was 80.3% and the former three rounds in this group got the best quality of signals with an identification rate of 85.7%, 85.1% and 88.0%, respectively, which was significantly higher than that of the latter three rounds. The identification rate of other probe was much lower than with the CEP probe (55.2% vs. 80.3%, P < 0.01) and the best quality of signal in this group was achieved in the fifth round (72.7%), followed by the second round (66.1%) and the third round (63.8%). The identification rate of the first round (50.3%) and the sixth round (22.2%) were significantly lower compared with the second round (P < 0.01). During the 6 rounds of FISH, 335 hybridizations did not give conclusion results (38.5%, 335/870). The main cause of unidentification was weak signals (20.9%, 182/870). Other common factors included background interference (7.6%, 66/870) and failed hybridization (6.1%, 53/870). Rare causes included nucleus damage (1.8%, 16/870), nucleus loss (1.1%, 10/870) and signal split/overlap (0.9%, 8/870).

CONCLUSIONMulti-round FISH can improve the utility of single nucleus in PGD and the former three rounds have the highest efficiency. The hybridization effect of CEP is better than other probe. Poor signal quality is the common cause of unidentification results.

Female ; Genetic Testing ; methods ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Male ; Pregnancy ; Preimplantation Diagnosis ; methods ; Prenatal Diagnosis ; Translocation, Genetic

Chromosomal mosaicism (CM) is a common phenomenon in preimplantation genetic testing (PGT). In embryos with CM, genetic contents of trophoblastic ectodermal (TE) cells may be different from that of the inner cell mass (ICM) which will develop into the fetus. Embryos with low mosaic proportion could give rise to healthy live births after transplantation, but are accompanied with high pregnancy risks such as high abortion rate. In order to provide a more comprehensive understanding for CM embryos, this article has systematically summarized the recent progress of research on the definition, mechanism, classification, PGT techniques, self-correction mechanism, transplantation outcome and treatment principles for CM embryos.
Pregnancy ; Female ; Humans ; Preimplantation Diagnosis/methods* ; Mosaicism ; Aneuploidy ; Genetic Testing/methods* ; Blastocyst

OBJECTIVE: To explore the influence of gender of chromosomal translocation carriers on the occurrence of embryonic chromosomal aberrations. METHODS: A retrospective study was carried out. Data were collected from 235 couples carrying reciprocal translocations (1163 blastocysts) and 70 couples carrying Robertsonian translocations (351 blastocysts). The preimplantation genetic testing for structural rearrangement (PGT-SR) analysis of 1514 blastocysts were completed through next generation sequencing (NGS). RESULTS: After adjusting the confounding factors such as female age, AMH, ovarian stimulation regimen, and Gn dosage, the results showed that the risk for blastocyst chromosomal abnormalities was 0.41 [OR(95%CI), 1.41(1.06, 1.87), P < 0.05] times higher in female reciprocal translocation carriers and 1.02 [OR(95%CI), 2.02 (1.20, 3.40), P < 0.01] times higher in female Robertsonian translocation carriers compared with male carriers, respectively. Compared with male carriers, the risk of blastocyst chromosomal abnormalities was increased by 0.67 times [OR(95%CI), 1.67 (1.10, 2.56), P < 0.05] in female reciprocal translocation carriers over 30 years old and 1.06 times [OR(95%CI), 2.06 (1.02, 4.15), P = 0.0434, P < 0.05] in female Robertsonian translocation carriers between 25 and 30 years old. CONCLUSION Compared with male carriers, female carriers of reciprocal or Robertsonian translocations have a higher risk for producing embryos with chromosomal abnormalities, and their age may also be a risk factor.
Adult ; Blastocyst ; Chromosome Aberrations ; Female ; Genetic Testing/methods* ; Humans ; Male ; Pregnancy ; Preimplantation Diagnosis/methods* ; Retrospective Studies ; Translocation, Genetic

OBJECTIVETo detect potential mutation of F8 gene in a family affected with hemophilia type A.

METHODSInverse-shifting PCR (IS-PCR), next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and short tandem repeat (STR) assays were used.

RESULTSIS-PCR showed that no inversion of F8 gene has occurred in the family. NGS detected no point mutation or small InDel in the proband, but suggested that the exon 2 of the F8 gene may be deleted. MLPA also showed that exon 2 of the F8 gene was absent in the proband, while the carriers were heterozygous for the deletion, though STR analysis yielded a paradoxical result.

CONCLUSIONNGS analysis has identified a large deletion of exon 2 of the F8 gene in a family affected with hemophilia A. Discretion is required when STR analysis was used for carrier screening and antenatal diagnosis. Combination of multiple methods can improve the accuracy for the detection of F8 gene mutations.

Child ; Exons ; genetics ; Factor VIII ; genetics ; Genetic Testing ; methods ; Hemophilia A ; Humans ; Male ; Pedigree ; Sequence Deletion ; genetics

Biomedical Technology ; Child ; Genetic Testing ; methods ; Humans ; Nervous System Diseases ; diagnosis ; genetics ; therapy ; Pediatrics ; Quality Improvement

OBJECTIVETo explore the feasibility of applying autosomal single nucleotide polymorphisms (SNPs) on parentage testing.

METHODSAll SNP genotyping results of HapMap (r27) were downloaded from the website. With self-made computer programs, SNPs were extracted when their minor allele frequency (MAF) were ≥ 0.30 among all of the 11 HapMap populations. Ninety-six SNPs were chosen and integrated into the Illumina Goldengate bead arrays on the condition that no linkage disequilibrium was found between them. Three father-child-mother trios (9 samples in total) were tested with the arrays. Cumulative paternity index (CPI) was then calculated and compared with genotyping results using 15 short tandem repeats (STRs)(Identifiler(TM)).

RESULTSFamily 1 was found to have nine SNPs or seven STRs that did not conform to the Mendelian laws, Family 2 had 13 such SNPs or seven STRs, and Family 3 only had one such SNP but no STR. For Family 3, when all of the 96 SNPs were used in combine, the CPI was 1207, which had contrasted with the CPI by the 15 STRs, i.e., 355 869.

CONCLUSIONWhen applied to paternity testing, the paternity exclusion (PE) value for a SNP is usually less than 1/3 of that of a STR. The proportion of SNPs not comforming to the Mendelian laws for the tested SNPs may not be as high as that of inconsistent STRs over all tested STRs. Because of the low mutation rate of a SNP, the CPI will be greatly reduced even if one SNP did not conform to the Mendelian laws. Therefore, highly accurate testing methods are required to reduce artificial errors when applying SNPs for paternity testing.

Fathers ; Female ; Genetic Testing ; methods ; Genotype ; HapMap Project ; Humans ; Male ; Mothers ; Paternity ; Polymorphism, Single Nucleotide ; genetics

OBJECTIVETo analyze the clinical features and pathological mutations in 44 families affected with hearing loss from southern Zhejiang, and to provide genetic counseling and prenatal diagnosis for 6 of the families.

METHODSMicroarray was employed to detect c.35delG, c.176del16, c.235delC and c.299-300delAT mutations of the GJB2 gene among 228 patients. For those carrying a single heterozygous mutation, the whole coding region of the GJB2 gene was analyzed by Sanger sequencing. For prenatal diagnosis, maternal DNA contamination was excluded by application of STR analysis.

RESULTSThe microarray assay has detected 49 patients with GJB2 mutations, which included 24 homozygous c.235delC mutations, 5 compound heterozygous c.235delC/c.176del16 mutations, 2 compound heterozygous c.235delC/c.299-300delAT mutations. Respectively, 16, 1 and 1 patients have carried single heterozygous c.235delC, c.176del16, and c.299-300delAT mutation. For the 16 patients, 7, 1, 1, 2, and 3 were detected by Sanger sequencing with a second heterozygous mutation of c.109G>A (2 of which were in conjunction with heterozygous c.176del16 and c.299-300delAT mutations), c.230G>A, c.427C>T, c.508-511 dupAACG, 79G>A+341A>G, respectively. Prenatal diagnosis revealed a compound heterozygous mutation in a fetus, heterozygous mutations in 4 fetuses, and no mutation of the GJB2 gene in 1 fetus.

CONCLUSIONThe proportion of carriers for GJB2 gene mutations in patients with hearing loss from southern Zhejiang has reached 21.5%. The c.235delC, c.176del16, and compound c.299-300delAT and c.109G>A mutations can cause moderate to severe hearing loss. In most affected families, Heterozygous mutations may be identified by sequencing the whole coding region of the GJB2 gene. Genetic analysis and prenatal diagnosis can prevent birth of further affected children.

Connexins ; genetics ; Female ; Genetic Testing ; methods ; Hearing Loss ; genetics ; Heterozygote ; Humans ; Male ; Mutation ; genetics ; Phenotype