Replication of the Association between Copy Number Variation on 8p23.1 and Autism by Using ASD-specific BAC Array

To discover genetic markers for autism spectrum disorder (ASD), we previously applied genome-wide BAC array comparative genomic hybridization (array-CGH) to 28 autistic patients and 62 normal controls in Korean population, and identified that chromosomal losses on 8p23.1 and on 17p11.2 are significantly associated with autism. In this study, we developed an 8.5K ASD-specific BAC array covering 27 previously reported ASD-associated CNV loci including ours and examined whether the associations would be replicated in 8 ASD patient cell lines of four different ethnic groups and 10 Korean normal controls. As a result, a CNV-loss on 8p23.1 was found to be significantly more frequent in patients regardless of ethnicity (p<0.0001). This CNV region contains two coding genes, DEFA1 and DEFA3, which are members of DEFENSIN gene family. Two other CNVs on 17p11.2 and Xp22.31 were also distributed differently between ASDs and controls, but not significant (p=0.069 and 0.092, respectively). All the other loci did not show significant association. When these evidences are considered, the association between ASD and CNV of DEFENSIN gene seems worthy of further exploration to elucidate the pathogenesis of ASD. Validation studies with a larger sample size will be required to verify its biological implication.

Chromosomal Alterations in Gastric Cancer Cell Lines Detected by Comparative Genomic Hybridization / 대한암학회지

PURPOSE: There are only a few cytogenetic studies in gastric cancer and so far no consistent specific chromosomal abnormalities have been described. In this study, we have used comparative genomic hybridization (CGH), a powerful molecular cytogenetic technique for detecting changes of the copy number throughout the genome, to screen for genetic alterations in gastric cancer cell lines. The CGH results were compared with those derived from G-banding and chromosome painting. MATERIALS AND METHODS: Conventional cytogenetic analysis was performed on five human gastric cancer cell lines, AGS, SNU-1, SNU-16, SNU-620, and SNU-719, by a G-banding staining technique. In CGH, equal amounts of differently labeled DNA from the cell lines and normal reference DNA were hybridized simultaneously to normal metaphase chromosomes. They were visualized by different fluorochromes, and the signal intensities were quantitated separately as gray levels along the single chromosomes. The over- and under- represented DNA segments were determined by computation of ratio images and average ratio profiles. To confirm the CGH results, fluorescence in situ hybridization (FISH) with chromosome specific painting was performed using indirectly labeled chromosome specific paints. RESULTS: Complex unbalanced chromosomal aberrations that could not be identified reliably by conventional cytogenetics in gastric cancer cell lines were successfully resolved by CGH analysis. CGH results were validated by using FISH with chromosome specific probes. In gastric cancer cell lines, gains of DNA copy number were more common than losses. Gains were detected on 1p, 1q, 2p, 3q, 6p, 7q, 10q, 11p, and 19q, and losses were observed on 4p, 4q, 5q, 12p, 12q, and 18q. Interestingly, all the five gastric cancer cell lines tested showed gain of DNA copy number on the chromosome 20, suggesting an existence of oncogene. CONCLUSION: Conventional cytogenetics, CGH, and FISH using painting probes represent complementary approaches that, when employed in combination, could greatly facilitate the comprehensive analysis of chromosomal imbalances in gastric cancer cell lines. Our results suggest the existence of an oncogene or oncogenes on chromosome 20 that play a role in the development and/or the progression of gastric carcinogenesis.

Clinical Analysis of 1,068 Cases of Mid-trimester Genetic Amniocentesis / 대한산부인과학회잡지

OBJECTIVES: The objective of this study is to analyze 1,068 cases of prenatal genetic amniocentesis and to compare the results with reported studies. METHOD: We analyzed 1,068 cases of midtrimester prenatal genetic amniocenteses from September 1994 to February 1999, and investigated the fetal chromosomal abnormality, obstetric outcomes and complications by the indications of genetic amniocentesis and prophylactic antibiotic use at the Department of Obstetrics and Gynecology, Ajou University School of Medicine. RESULTS: Abnormal maternal serum markers were the most common indication of amniocentesis (57.7%) and the most common age distribution was 25-29 years (39.2%). One case of early amniocentesis (14 gestational weeks) was performed. The overall incidence of chromosomal aberration was 5.2% (56/1,068), of which there were 28 cases (50.0%; 28/56) of numerical aberrations and 28 cases (50.0%; 28/56) of structural aberrations. There were 50 cases (4.7%) of autosomal chromosomal aberrations and 6 cases (0.6%) of sex chromosomal aberrations. The pregnancy outcome was full-term delivery in 86.5%, preterm delivery in 7.6%, termination of pregnancy in 4.0%. There were no cases of serious complications including fetal death except for a case of self-limited amniotic fluid leakage(high leakage) in which the pregnancy was maintained. There were no significant differences between prophylactic antibiotics user group and non-user group in obstetric complications and outcomes. CONCLUSION: We could confirm that the trend in the indication of genetic amniocentesis had changed from advanced maternal age(35 year-old) toward abnormal maternal serum marker(triple test), and we recognized the importance of genetic amniocentesis according to the various antenatal screening tests of maternal serum marker, antenatal ultrasound, past history of fetal anomaly or family history of fetal chromosomal anomaly in the younger age groups(< 35 year-old) that are involved in more than half of the chromosomal anomaly. Further study will be needed to elucidate the efficacy of using prophylactic antibiotics in amniocentesis.