Deniz Taştemir

Chromosome aberrations in a schizophrenia population

Cytogenetic abnormalities with schizophrenia may provide a valuable clue to the identification of target loci and successful search for major genes. We have performed chromosomal examinations by using the GTG banding technique on 134 schizophrenics. In 43 patients (32%), random numerical and structural aberrations were detected. Structural aberrations predominated and usually consisted of deletions and inversion of various chromosomes. Numerical changes were present in one or two cells in 14 cases including trizomy 21, marker and acentric chromosomes, and 47,XXY. The seven cases with pericentric inversion and enlargement of the heterochromatin region of chromosome 9 (inv(9); 9qh+) were observed in the study. The incidence (5.2%) of inv(9) and 9qh+ in our schizophrenic patients were found higher than the general population, suggesting that a susceptibility locus for schizophrenia may be located at pericentromeric region of chromosome 9. Our study have detected 1q21, 7q23, inv(9), 9qh+, 11q23, 21q22, 22q11-13 and Xp11-q13 suggested that these chromosomal lesions are prevalent in schizophrenics. The reason for this might be that these anomalies increase risk for schizophrenia in a relatively nonspecific way, such as contributing to disruption of normal embryogenesis of the nervous system.

Chromosomal fragile sites in schizophrenic patients

Schizophrenia is a common and complex mental disorder. Cytogenetic and molecular studies have shown that genetic factors play an important role in the etiology of schizophrenia. As a preliminary step in the search for chromosomal location of a susceptible gene predisposing to schizophrenia, cytogenetic screening of patients might be useful. Therefore, this report is aimed at studying the relationship between chromosomal fragile sites (FS) (gaps, breaks, triradial figures, and several rearrangements) and the etiology of schizophrenia. Because of this, we compared the frequencies of folate-sensitive FS from schizophrenic patients and normal individuals in short-term whole-blood cultures. The rate of FS expression in the patients was considerably higher than in the controls. We determined 15 common FS (cFS) (1q21, 1q32, 2q21, 2q31, 3p14, 4q31, 5q31, 6q21, 6q26, 7q22, 7q32, 10q22, 13q32, Xp22, and Xq22), six rare FS (rFS) (6p21, 8q22, 11q23, 12q24, 16q22, and Xq26), and two previously unknown FS (3p25 and 5q22). Among these expressed FS, there was a significantly higher frequency of 12 FS at 2q31, 3p25, 3p14, 5q31, 6q21, 7q22, 7q32, 10q22, 11q23, 12q24, Xq22, and Xq26 in patient group than in controls by x2-test (P between 0.0001 to 0.036). Sites 3p14, 5q31, and 7q22 were also the most frequently observed cFS. Males exhibited twice as many FS as females, but no age effects were observed. The potential relationship between increased FS frequency and the occurrence of schizophrenia in these patients is discussed.

Cytogenetic effects of ethanol on chronic alcohol users.

AIM Alcoholism is a significant public health problem that is also associated with a complex genetic trait. Fragile sites (FS) are potentially informative endpoints for the study of clinical disorders. We aimed to find chromosomal damages in chronic alcohol users for the purpose of finding the correlation between alcohol and chromosomal anomalies. METHODS The potential roles/effects of ethanol on chromosome(s) were assessed in this study by investigating its cytotoxic effects in lymphocyte cultures from chronic alcoholics and controls. RESULTS Alcoholics revealed a significantly higher frequency of FS and chromosomal aberrations (CA), and the FS clusters in specific chromosomal regions: 1q12, 1q21, 1q32, 2p13, 2q21, 2q31, 3p14, 3p25, 3q21, 4q21, 4q31, 5q31, 6p21, 7q22, 7q32, 9q13, 9q22, 10q22, 11q23, and 12q13. We also observed a significantly greater number of numerical and structural CA in alcoholics. The most frequent exchange types were deletions and polymorphic variations. CA could be due to the cumulative effect of both alcohol and smoking. The loci 1q12, 3p25, 4q31, 6p21, and 12q13 were not reported previously in alcoholics and may be hot spots for alcoholism. The overall FS frequencies were not statistically different between smoker and non-smoker controls, but smoking significantly increased the expression of 1p36, 3q21, and 5p15 sites. These sites have important clinical significance. CONCLUSIONS Chronic alcohol abuse and the smoking habit can lead to chromosome damages that are especially influential on oncogenic regions, which may persist for a long time, and constitute a relevant factor of risk for the development of neoplasias.

Cytogenetic study of recurrent miscarriages and their parents.

There is substantial evidence that genetic alterations are contributing factors to the risk for recurrent miscarriages. This study was conducted to determine the frequency and contribution of chromosomal abnormalities in miscarriages and in couples with recurrent miscarriages. We studied a total of 41 miscarriages and their parents with a history of 2–11 recurrent miscarriages. Chromosomal analysis from chorionic villus sampling (CVS) and fetal tissues were performed according to standard cytogenetic methods using G-banding technique. Major chromosomal aberrations and polymorphic variants were found in 51 and 4.8%, respectively. The chromosomal abnormalities were structural (34.4%) and numerical (65.1%) of which 26.1, 21.7, 8.7 and 8.7% were fetal sex aneuploid, triploid, mosaics and trisomic, respectively. Unbalanced and balanced rearrangements were found in 17.2 and 8.6% of all abnormalities, respectively. Major chromosomal abnormalities in couples were seen in 4.9%. The chromosomal abnormalities associated with pregnancy losses and recurrent miscarriages are mostly numerical ones. The incidence of balanced translocations found here is 4.9% which is near to the mode (about 3–6%) observed in the previous studies. Those frequencies are greater than in the general population (0.3%). This indicates that balanced translocations, seen in parents, have some importance in causing miscarriage. The major parental chromosomal aberrations are significantly associated with fetal wastage. Mosaicism should be taken into account for cytogenetic analyses of pregnancy losses. Thus, cytogenetic analyses should be recommended in couples with recurrent miscarriages, when clinical data fail to clarify the cause.

Chromosomal fragile site expression in Turkish psychiatric patients

Chromosomal aberrations associated with psychiatric disorders may suggest regions in which to focus a search for genes predisposing to psychosis by a linkage strategy. Identification of these may be especially important given the unknown pathophysiology and the probable genetic heterogeneity of psychiatric disorders. In this study, the frequencies of folate sensitive fragile sites (FS) were compared among psychiatric disorders (e.g., schizophrenia, bipolar disorder, and other psychosis) and normal individuals. The rate of FS expression in the patients was considerably higher than in the controls. Sites 1p22, 1q21, 1q32, 2q31, 3p14, 3p25, 5q22, 5q31, 6p21, 6q21, 6q25, 7q22, 7q32, 8q22, 10q21, 11q23, 12q24, 13q32, 14q24, 16q22, 17q21, Xp22 and Xq26 were expressed more frequently in the patients. Thirty possible relevant chromosomal sites were identified in schizophrenia: 1q21, 1q32, 2p13, 2q21, 3p14, 3p25, 3q21, 5q22, 5q31, 6p21, 6q25, 6q26, 7q21, 7q22, 7q32, 8q22, 9q21, 10q21, 11q23, 12q24, 13q32, 14q24, 16q22, 17q21, Xp22, Xq22, and Xq26. Possible relevant sites were also identified in bipolar disorder: sites 1p36, 1q21, 1q32, 3p14, 3p25, 5q31, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22, and Xq26. Sites in the other psychosis group were: 1p22, 1p32, 1p36, 1q21, 1q32, 2q31, 3p14, 3p25, 5q31, 6p21, 6q21, 6q25, 6q26, 7q22, 7q32, 8q22, 10q21, 11q23, 12q13, 12q24, 13q32, 16q22, 16q24, 17q21 and Xq26. Among patient groups, there were significant differences in bands 1p32, 2p13, 2q21, 2q31, 3p14, 3p25, 5q31, 6q21, 6q26, 7q22, 7q32, 9q21, 11qq23, 12q13, 12q24, 16q24, and Xq22 between schizophrenic and bipolar patients. These regions were more frequently expressed in schizophrenic patients than in bipolar patients. The 1p22, 1p32, and 16q24 regions were significantly more frequently expressed in the other psychosis group than in the bipolar group. These interesting regions, which may harbor important genes for psychosis, have produced strong support for linkage in the majority of genome scan projects.

The expression of folate sensitive fragile sites in patients with bipolar disorder.

Purpose Genetic factors are known to be important in the etiology of bipolar disorder (BD). The fragile sites (FSs) are a very interesting subject for the study of clinical disorders. The aim of this study was to evaluate fragile sites seen in patients with bipolar disorder and find a correlation between some fragile sites and bipolar disorder. Patients and Methods The frequencies of folate sensitive FSs were compared in short-term whole blood cultures from bipolar patients and from normal individuals. Results The rate of FS expression in the patients was considerably higher than in the controls (p < 0.001). Several chromosome regions including 1p36, 1q21, 1q32, 3p25, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22 and Xq26 were represented considerably more often in the patients than in the controls (p value between 0.001 to 0.036). Among these FSs, the sites 1p36, 1q21, 3p25, 7q22, 7q32, and 14q24 were not observed in other studies. Conclusion These regions can be the most active of hot spots in the genomes of bipolar patients, and may harbor important genes associated with BD.

Detection of Parental Origin and Cell Stage Errors of a Double Nondisjunction in a Fetus by QF-PCR

AIM To investigate parental origins and cell stage errors of a double nondisjunction in a fetus. METHOD For the determination of the most common chromosome anomalies, quantitative fluorescent polymerase chain reaction method using short tandem repeat (STR) DNA markers was applied to a fetus with abnormal ultrasonographic findings. Parental origin and cell stage errors of the trisomies were inferred by comparing the inherited STR alleles. Conventional cytogenetic technique was also applied for the confirmation of the aneuploidies. RESULTS A double nondisjunction including chromosomes 21 and X (48,XXX,+21) was detected prenatally in the fetus. The origin of both chromosomes was maternal, and the errors were in meiosis I for 21 and meiosis II for X. Molecular results were concordant with cytogenetic results. CONCLUSION Molecular techniques could be useful for the pre- and postnatal diagnosis of the common aneuploidies and determining its parental origin. This kind of study will improve knowledge about the mechanisms of nondisjunction and enable appropriate and rapid genetic counseling.

The Reliability of Maternal Serum Triple Test in Prenatal Diagnosis of Fetal Chromosomal Abnormalities of Pregnant Turkish Women

AIM The purpose of this article was to evaluate the reliability of maternal serum triple marker screening of alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol for the prenatal diagnosis of fetal chromosomal abnormalities in Turkish pregnant women. METHOD Medical records were used to analyze indications of amniocentesis and quantitative fluorescent-polymerase chain reaction. Anomaly screening was performed for all patients between 13 and 22 weeks of pregnancy. A total of 1725 pregnancies with chromosomal abnormality risk according to triple test screening were accepted for fetal chromosome analysis and quantitative fluorescent-polymerase chain reaction. RESULTS Chromosomal aberrations were observed in 56 (3.2%) cases. About 44.6% of the abnormalities detected were numerical aberrations; however, 55.3% of the abnormalities were structural aberrations. Abnormalities detected were inversion of chromosome 9 in 20 cases, trisomy 21 in 14 cases, 46,XX/47,XX, +21 in 1 case, trisomy 18 in 2 cases, trisomy 13 in 1 case, 47,XXY, in 1 case, 45,X, in 1 case, structural abnormalities in 12 cases, and mosaic or tetraploidy in 6 cases. CONCLUSION Second trimester triple test is an effective screening tool for detecting fetal Down syndrome in Turkish women.

Çukurova Populasyonunda Gebelik Zamanı ve Maternal Yaşın Fetal Cinsiyet Oranı Üzerine Olan Etkisi

Amac: Bu calismanin amaci, cukurova ve cevresindeki populasyonda konsepsiyon ayi, ebeveynlerin yaslari, mevsimsel degisimler, ebeveynlerin alkol ve sigara kullanim durumlari gibi cevresel degiskenlerin fetal cinsiyet oranini etkileyip etkilemediklerini tespit etmektir. Materyal ve Metod: Bu calismada, 2005-2007 yillari arasinda amniyosentez maksadiyla prenatal tani laboratuvarimiza yonlendirilen hastalarin verilerini analiz ettik. Istatistiksel analiz icin ki-kare, Fishers exact ve T testlerini uyguladik. Bulgular: Konsepsiyon zamani ile primer cinsiyet orani arasinda bir iliski tespit edilemedi. Aylara gore primer cinsiyet oranindaki degisimlerin istatistiksel olarak anlamli olmadigi gozlendi. Istisna olarak eylul ayindaki degisim kaydedildi. Eylul ayinda istatistiksel olarak anlamli bir sekilde cinsiyet oraninin erkege dogru degistigi saptandi (erkek:kadin orani=1.8). Sonuc: Yaz/sonbahar fotoperiyodunda bulunan eylul ayindaki iklimsel degisimin, cinsiyet oranindaki bu farklilasmayi etkiledigini dusunmekteyiz.