Genetic epidemiology studies have established that the natural variation of gene expression profiles is heritable and has genetic bases. A number of proximal and remote DNA variations, known as expression quantitative trait loci (eQTLs), that are associated with the expression phenotypes have been identified, first in Epstein-Barr virus-transformed lymphoblastoid cell lines and later expanded to other cell and tissue types. Integration of the eQTL information and the network analysis of transcription modules may lead to a better understanding of gene expression regulation. As these network modules have relevance to biological or disease pathways, these findings may be useful in predicting disease susceptibility.
Cell Line ; Disease Susceptibility ; DNA ; Gene Expression Regulation ; Metagenomics ; Molecular Epidemiology ; Phenotype ; Quantitative Trait Loci ; Transcriptome

Waardenburg syndrome (WS) is a clinically and genetically heterogeneous hereditary auditory pigmentary disorder characterized by congenital sensorineural hearing loss and iris discoloration. Many genes have been linked to WS, including PAX3, MITF, SNAI2, EDNRB, EDN3, and SOX10, and many additional genes have been associated with disorders with phenotypic overlap with WS. To screen all possible genes associated with WS and congenital deafness simultaneously, we performed diagnostic exome sequencing (DES) in a male patient with clinical features consistent with WS. Using DES, we identified a novel missense variant (c.220C>G; p.Arg74Gly) in exon 2 of the PAX3 gene in the patient. Further analysis by Sanger sequencing of the patient and his parents revealed a de novo occurrence of the variant. Our findings show that DES can be a useful tool for the identification of pathogenic gene variants in WS patients and for differentiation between WS and similar disorders. To the best of our knowledge, this is the first report of genetically confirmed WS in Korea.
Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group/genetics ; Base Sequence ; DNA/chemistry/genetics/metabolism ; Exons ; Humans ; Male ; Mutation, Missense ; PAX3 Transcription Factor/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Republic of Korea ; Sequence Analysis, DNA ; Waardenburg Syndrome/*diagnosis/genetics

Chromosomal loss in trisomy (trisomy rescue) to generate a disomic fetus can cause confined placental mosaicism and/or feto/placental mosaicism. After trisomy rescue event, there is a risk of fetal uniparental disomy (UPD). Noninvasive prenatal test (NIPT) reflects the genomic constitution of the placenta, not of the fetus itself. Feto-placental discrepancy can therefore cause false-positive (trisomy) NIPT results. These discordant NIPT results can serve as important clues to find UPD associated with confined placental mosaicism. We report a case with maternal UPD of chromosome 20, detected by NIPT of 1,000 high-risk pregnancies, carried out for detecting chromosomal abnormalities in Koreans.
Chromosome Aberrations ; Chromosomes, Human, Pair 20* ; Constitution and Bylaws ; Fetus ; Mosaicism ; Placenta ; Pregnancy, High-Risk* ; Trisomy ; Uniparental Disomy*

Purpose: This study explored the potential feasibility of cell-free DNA (cfDNA) in monitoring treatment response through the measurement of chromosomal instabilities using I-scores in the context of radiation therapy (RT) for other solid tumors. Materials and Methods: This study enrolled 23 patients treated with RT for lung, esophageal, and head and neck cancer. Serial cfDNA monitoring was performed before RT, 1 week after RT, and 1 month after RT. Low-depth whole-genome sequencing was done using Nano kit and NextSeq 500 (Illumina Inc.). To measure the extent of genome-wide copy number instability, I-score was calculated. Results: Pretreatment I-score was elevated to more than 5.09 in 17 patients (73.9%). There was a significant positive correlation between the gross tumor volume and the baseline I-score (Spearman rho = 0.419, p = 0.047). The median I-scores at baseline, post-RT 1 week (P1W), and post-RT 1 month (P1M) were 5.27, 5.13, and 4.79, respectively. The I-score at P1M was significantly lower than that at baseline (p = 0.002), while the difference between baseline and P1W was not significant (p = 0.244). Conclusion We have shown the feasibility of cfDNA I-score to detect minimal residual disease after RT in patients with lung cancer, esophageal cancer, and head and neck cancer. Additional studies are ongoing to optimize the measurement and analysis of I-scores to predict the radiation response in cancer patients.