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Mozaik trizomi 17 nadir görülen otozomal trizomilerden olup literatürde sadece 30 olguda bildirilmiştir. Olguların büyük çoğunluğu “chorionic villus sampling” (CVS) ve amniyosentez materyallerinden yapılan prenatal genetik analizlerde saptanmış olup klinik bulgular son derece değişkendir. Burada sunduğumuz olgunun prenatal dönemde ultrasonografik takibinde lateral ventriküllerde sınırda ventrikülomegali saptandı ve amniyosentez yapıldı. Sitogenetik analiz ile karyotip 47,XX,+17[5]/46,XX[35] olarak saptandı. Yapılan FISH analizi ile mozaik trizomi 17 karyotip bulgusu doğrulandı (nuc ish(RARA×3,PML×2)[30/100], (TP53×3)[35/100]). Termde spontan vajinal yolla doğan olgunun fizik muayenesinde ve transfontanel ultrasonografisinde herhangi bir dismorfik bulgu ya da konjenital anomali saptanmadı. Periferik kandan postnatal olarak yapılan kromozom analizinde karyotip 46,XX olarak saptandı. Periferik kandan ve yanak mukozasından lokus spesifik problar ile yapılan FISH analizinde de mozaisizm saptanmadı (nuc ish(RARA,PML)×2[200],(TP53×2)[200]). Prenatal tanıda nadir görülen mozaik trizomi 17 saptanan olgumuz, ileride karşılaşılabilecek benzer olgularda ailelere verilecek genetik danışmanlık açısından katkı sağlayacaktır., Mosaic trisomy 17 is rarely observed and about 30 cases have been reported so far. Most of the cases have been identified by genetic diag-nostic analysis of chorionic villus sampling (CVS) and amniotic fluid in the prenatal period. Clinical manifestations are extremely variable. In the case presented here, due to the size of lateral ventricles was seen at the upper limit of normal range in the prenatal ultrasonographic investigation, amniocynthesis was performed and the karyotype was found as 47,XX,+17[5]/46,XX[35]. This mosaicism was confirmed by FISH analysis also (nuc ish(RARA×3,PML×2)[30/100],(TP53×3)[35/100]). The baby was born by spontaneous vaginal delivery at term. No dysmorphic feature or congenital anomaly has been observed in the physical examination or in trans-fontanel ultrasonographic examination. Peripheral blood karyotype was found 46,XX. The mosaicism was not diagnosed in FISH analysis of peripheral blood and buccal mucosa samples using spesific probes, too (nuc ish(RARA,PML)×2[200],(TP53×2)[200]). This case report demonstrating uncommon mosaic tri-somy 17 would be useful to give genetic counseling to the families having similar cases in the future.

Oxidative stress plays an important role in the development of type 1 diabetes(T1D) and its complications. Glutathione-S-Transferases (GST) is one of the defense systems against the harmful effects of oxidative stress. In our study, we aimed to investigate the relationship between GSTT1 and GSTM1 gene polymorphisms and Turkish patients with T1D. In our study, 71 patients were diagnosed with T1D and 62 control subjects were included. GSTM1 and GSTT1 gene polymorphisms were used to evaluate the multiplex PCR method.In statistical analysis, the level of significance was set at p0.05). These results show that GSTT1 and GSTM1-negative (null) genotypes may not contribute to the development of T1D and its complications but more studies with larger sample size are needed., Oksidatif stres, tip 1 diyabet (T1D) ve komplikasyonlarının gelişiminde önemli bir rol oynamaktadır Oksidatif stresin zararlı etkilerine karşı savunma sistemlerinden biri de Glutatyon-S-Transferaz (GST)'dır. Çalışmamızda, GSTT1 ve GSTM1 gen polimorfizmleri ile T1D'li Türk hastalar arasındaki ilişkiyi araştırmayı amaçladık. Çalışmamıza, T1D tanısı konmuş 71 hasta ile 62 kontrol birey dahil edildi. GSTM1 ve GSTT1 gen polimorfizmini değerlendirmek için multiplex PCR yöntemi kullanıldı. İstatistiksel analizde anlamlılık düzeyi p 0.05). Bu sonuçlar GSTT1 ve GSTM1 negatif(null) genotiplerinin T1D ve komplikasyonların gelişimi için katkısının olmadığını göstermektedir fakat daha geniş olgu sayılı çalışmalara ihtiyaç vardır.

In this study, the genotoxic effects of benzalkonium chloride, widely used as a disinfective and protective agent, were investigated using micronucleus assay. Whole blood lymphocyte cultures, prepared from healthy, non-smoking male donors were used in the study. The cul-tures were treated with 6 different concentrations of benzalkonium chloride (0.04 mg/L, 0.11 mg/L, 0.33 mg/L, 1 mg/L, 3 mg/L, and 9 mg/L) and the effects on micronucleus formation were investigated. Three healthy donors were included in the study and the experiments were done using two cultures for each concentration. Micronuclei were scored examining 1000 binucleated cells for each culture. When compared to negative control, none of the tested concentrations led to a significant increase in micronucleus levels. In conclusion, ben-zalkonium chloride showed no significant genotoxic effects under our experimental conditions., Bu çalışmada, dezenfektan ve koruyucu özelliğinden dolayı çok yaygın olarak kullanılan benzalkonyum klorürün genotoksik etkisi in vitro mikronükleus testi ile araştırıldı. Çalışmada, herhangi bir genotoksik ajana maruz kalma öyküsü bulunmayan ve sigara kullanmayan sağlıklı erkek gönüllülerden hazırlanan tam kan lenfosit kültürleri kullanıldı. Kültürlere 6 farklı konsantrasyonda (0.04 mg/L, 0.11 mg/L, 0.33 mg/L, 1 mg/L, 3 mg/L ve 9 mg/L) benzalkonyum klorür ilave edilerek mikronükleus oluşumuna etkisi araştırıldı. Deneyler üç sağlıklı gönüllü ile ve her konsantrasyon için ikişer kültür hazırlanarak çalışıldı. Her kültürden 1000 binükleer hücre değerlendirilerek mikronükleus analizi yapıldı. Negatif kontrol kültürlerinden elde edilen sonuçlar ile yapılan karşılaştırma sonucunda, çalışılan konsantrasyonların hiçbirinde mikronükleus değerlerinde anlamlı artış gözlenmedi. Sonuç olarak uygulanan in vitro kültür koşullarında benzalkonyum klorürün anlamlı genotoksik etkisi tespit edilmedi.

In this study, the results of conventional cytogenetic and FISH analysis of 200 cases who were admitted for prenatal diagnosis in 2004-2008 were grouped and evaluated according to the indications as abnormal ultrasound findings, triple test risk, advanced maternal age and the others. Subgroups were designated according to the additional indications. In evaluated 200 cases, 52 cases referred for advanced maternal age, 59 cases for abnormal ultrasound findings, 44 cases for triple test risk, 11 cases for other indications. Numerical chromosomal aberration ratio was observed higher in the group with abnormal ultrasound findings than the other groups without abnormal ultrasound findings (p=0.002). In prenatal diagnosis, application of the rapid assays such as FISH is very important and necessary especially in cases who have late amniocentesis and abnormal ultrasound findings because of shortening the result giving time, taking possible termination time earlier, decreasing mother's waiting stress, saving time for additional tests., Bu çalışmada, 2004-2008 yılları arasında prenatal tanı amacı ile gelen 200 hastanın konvansiyonel sitogenetik ve FISH analiz sonuçları sayısal kromozomal anomaliler yönünden endikasyonlarına göre; anormal ultrason bulgusu (AUS), üçlü tarama testi riski (ÜTT), ileri maternal yaş (İMY) ve diğerleri olarak dört ana grupta ve ek endikasyonlara göre de alt gruplarda değerlendirildi. Değerlendirilen 200 vaka içinde, 52 vaka ileri maternal yaş, 59 vaka anormal ultrason bulgusu, 44 vaka üçlü tarama test riski nedeniyle gönderilmişti. Diğer endikasyonlarla gelen vakaların sayısı ise 11 olarak tespit edildi. AUS ile gelen vakalarda sayısal kromozomal anomali oranı AUS içermeyen vakalara göre daha yüksek bulundu (p=0.002). AUS olan ve özellikle geç dönemde amniyosentez yapılan olgularda, konvansiyonel sitogenetik analize ek olarak FISH gibi hızlı sonuç alınan yöntemlerin uygulanmasının sonuç verme süresinin kısaltılabilmesi, olası terminasyonun erkene alınması, annenin bekleme stresinin azaltılması, ilave tetkik yapılacaksa zaman kazanılması gibi önemli yararlar sağlaması nedeniyle oldukça etkili ve gerekli olduğu gözlendi.

Chromosomal numerical aberrations and translocations are often the first or initiating events in childhood leukemias. The specific genetic changes in childhood leukemias are important to diagnose the disease and to monitor the response to the treatment. Furthermore, these kind of genetic alterations form an important indicator for the prognosis of the diseases. Therefore, the detection and the genetic classification of these specific genetic alterations in childhood leukemias would help clinicians for the diagnosis, treatment, and monitoring the prognosis of the disease as well as applying novel therapeutic approaches., Kromozomal sayısal düzensizlikler ve translokasyonlar genelde çocukluk çağı lösemilerinin başlangıcındaki olaylardır, yada hastalığın oluşmasını sağlayan ilk olaylardır. Çocukluk çağı lösemilerine özgü spesifik genetik değişiklikler, hastalığın tanısı ve tedaviye yanıtın izlenmesi açısından oldukça önemlidir. Bu genetik değişiklikler aynı zamanda hastalığın prognozu açısından da önemli bir gösterge oluşturmaktadır. Böylece, bu spesifik genetik değişikliklerin tespiti ve sınıflandırılması klinisyenlere hastalığın tanısı, tedavisi, prognozunun takibi ve yeni terapötik yaklaşımların uygulanması açısından yardımcı olacaktır.

Otozomal resesif osteopetrozis ORO genellikle infant veya çocukluk çağında ölüme yol açan ciddi bir hastalıktır. TNFSF11 geni tarafından kodlanan RANKL ve TNFRSF11A geni tarafından kodlanan RANK proteinleri osteoklast olgunlaşması için önemli olup bu genlerdeki mutasyonların ORO gelişiminde rol oynadığı gösterilmiştir. Bu yazıda aralarında akrabalık bulunan eşlerin 2 çocuğunda da TNFRSF11A geninde c.508 A→G homozigot mutasyonu pArg170Gly saptanmış. Bir sonraki gebelik sırasında CVS materyali üzerinde yapılan mutasyon analizinde, fetusta heterozigot mutasyon saptandı. Gebelik terme kadar devam etti ve sağlıklı bir erkek çocuk doğdu. Prenatal mutasyon analizi, mutasyonu bilinen hastalıklarda ebeveynin anksiyetesini rahatlatmak ve aileye genetik danışma vermek için önemlidir, Autosomal recessive osteoporosis ARO is a severe disease causing death usually at infancy or childhood. RANKL coded by TNFSF11 gene and RANK coded by TNFRSF11A gene are important proteins for osteoclast maturation and it is indicated that mutation on these genes plays an important role for ARO development. It is reported in this article that c.508 A→G homozygote mutation pArg170Gly is observed in TNFRSF11A gene of 2 children of consanguineous couple. Mutation analysis performed on CVS material during the next pregnancy revealed heterozygous mutation in the fetus. The pregnancy was continued to term and a healthy boy was delivered. Prenatal mutation analysis is important for diseases with known mutations to relieve parental anxiety and provide genetic counselling for the family

The EGFR gene and ALK rearrangements are two genetic drivers of non-small cell lung cancer (NSCLC). The frequency of EGFR mutations and ALK rearrangement varies according to not only ethnicity but also gender, smoking status and the histological type of NSCLC. In the present study, we demonstrated the distribution of EGFR mutations in 132 NSCLC patients by using a pyrosequencing technique and the distribution of ALK rearrangements in 51 NSCLC patients by using fluorescent in situ hybridization technique in Turkey. Additionally, we compared the clinicopathological data of NSCLC patients with the mutation status of EGFR in their cancerous tissues. Both EGFR mutations and ALK rearrangements were identified in 19 (14.39 %) and 1 (1.96 %) patients, respectively. We found EGFR mutations in codon 861, 719 and 858 with the ratios of 10.52 % (2/19), 10.52 % (2/19) and 31.58 % (6/19), respectively, and deletion of exon 19 in 47.37 % (9/19) of the patients. We found the frequency of EGFR mutations to be significantly higher in female patients and nonsmokers (p = 0.043, p = 0.027, respectively). Consequently, we found EGFR mutations to be more frequent in female patients and nonsmokers. Future studies on larger patient groups would provide more accurate data to exhibit the relationship between EGFR mutations and ALK rearrangements and the clinicopathological status.

Colchicine is commonly used in the treatment of Behçet's disease. However, some patients are unresponsive to colchicine treatment. Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transports colchicine out of cells. We investigated a possible association of C3435T polymorphism of the ABCB1 (MDR1) gene with colchicine response in patients with Behçet's disease. We randomly selected 97 patients with Behçet's disease, examined ABCB1 (MDR1) gene C3435T polymorphisms, and evaluated patient responses to colchicine. Forty-three patients were colchicine responsive, while the remaining 54 patients were unresponsive. No significant difference was found between genotypic and allelic frequencies of the ABCB1 C3435T polymorphisms in patients with Behçet's disease and healthy volunteers. Also, there was no significant difference among responsive and nonresponsive patients. We concluded that ABCB1 C3435T polymorphism is not associated with a colchicine response in patients with Behçet's disease.

Myeloid/lymphoid leukemia (MLL) gene rearrangements are high risk cytogenetic characteristics of acute lymphoblastic leukemia (ALL). Translocations of this gene are well defined, and their impact on the patient's prognosis is well known, but deletions of the same region are rare, and little is known about their prognostic significance and the significance of their accompanying translocations. Here we present a case of childhood ALL with a deletion of the 5' region of the MILL gene detected by fluorescence in situ hybridization (FISH) analysis, This result also confirmed the sensitivity and efficiency of FISH analysis.

Although it is well known that numerical and structural chromosomal aberrations are common in leukemic cells, tetraploidy and near-tetraploidy is a rare entity in acute myeloid leukemia (AML) [1-4]. We describe a rare case of AML-M0 with near-tetraploidy and superior vena cava syndrome (SVCS) due to a large mediastinal granulocytic sarcoma (GS). A 25-year-old male was admitted to our hospital with a progressive non-productive cough, dyspnea, pain on the left upper extremity and weight loss. One month ago, he was treated with a diagnosis of venous thrombosis because of the pain and swelling on his left upper extremity. At the time of admittance, physical examination revealed dyspnea, facial edema, swelling of the neck and upper extremities and dilated jugular and superficial veins of the chest. Peripheral lymph node or organomegaly was absent. His hematological findings were: hemoglobin, 14.1 g dl−1; hematocrit, 41.6%; MCV, 87.5 fl; WBC, 15.3 × 109 l−1 with 15% polymorphonuclear cells; 22% bands; 37% lymphocytes; 26% resembling blastic cells; and platelets 284 × 109 l−1. The chest X-ray showed enlarged mediastinum and thorax computed tomography (CT) demonstrated a multi-lobar mass with a diameter of 9 × 5 cm in the anterior mediastinum which also compressed the superior vena cava (Figure 1A). Abdominopelvic CT scan was normal. Mediastinoscopy was performed for definite diagnosis. The biopsy specimens from mediastinal mass revealed diffuse malignant infiltration in lipomatous tissue, which consisted of round, large sized cells. Nuclei were large, vesicular and contained two or three nucleolus. Cytoplasm was moderate in amount and clear. The specimens showed negativity for all of the antibodies and staining except for myeloperoxidase (MPO), CD34 and TdT (Figure 1B). Bone marrow aspirate revealed the presence of large blasts with a relatively low nuclear-cytoplasmic ratio, moderate chromatin pattern, two-to-three prominent nucleoli, no cytoplasmic granules and few cytoplasmic vacuolization. Most of the cells had heterogeneous shaped nuclei. No Auer rod was seen (Figure 1C). Cytochemistry revealed negativity for MPO, Sudan black B, periodic acid Schiff, combined esterase and acid phosphatase. Flow cytometric studies of the bone marrow cells revealed positivity for CD13, CD33, CD34, CD45, CD7 and HLA-DR. Cytogenetic analysis showed near tetraploidy (Figure 1D). Results of cytogenetic analysis of 20 metaphases of the bone marrow cells were as follows; 102, XXYY, +13, +14, +14, +15, +16, +18, +19, +21, +21, +22 [6] / 104, XXYY, +X, +Y, +3, +4, −7, −8, +10, +11, +13, +13, −14, +15, +15, +19, +21, +21, +22, +22 [9] / 98, XXYY, +3, +4, −6, +8, −11, +13, +14, −16, +19, +20, +21, +21 [5]. Neither apparent structural rearrangement nor normal clone was identified. Upon establishing the diagnosis (AML-M0/near tetraploidy+/mediastinal GS+) [5], he was given an induction chemotherapy consisting of daunorubicin (45 mg m−2 per day, days 1–3) and cytarabine (100 mg m−2 per day continuous infusion, days 1–7) and bone marrow remission was achieved. Then, he received the first consolidation chemotherapy consisting of idarubicin (10 mg m−2 per day, days 1–3) and cytarabine (1000 mg m−2 per day, days 1–6), followed by second consolidation chemotherapy consisting of cytarabine (6 gr m−2 per day, days 1–3) and 1800 cGy radiotherapy on mediastinum. The symptoms of SVCS improved gradually after the 5th day of induction chemotherapy. Likewise, the mediastinal mass decreased in size by 30% after induction chemotherapy, 70% after consolidation chemotherapies and disappeared completely after the completion of radiotherapy (Figures 1E and F). Presently, he is in the 10th month of his complete remission without any recurrence in the disease or GS.

The role of age, gender and smoking on both the genotoxic effects of Helicobacter pylori and the efficacy of eradication therapy in a group of patients with gastritis was investigated. Gastritis was confirmed by endoscopy and biopsy, and the presence of H. pylori by urease testing. Pre- and post-treatment peripheral blood lymphocyte cultures were prepared from 17 patients and 25 metaphases per patients were analysed for sister chromatid exchange (SCE), a well-established technique for the evaluation of human exposure to toxic agents. Treatment with omeprazole, clarithromycin and amoxycillin triple therapy eradicated H. pylori in 94% of patients and significantly reduced the SCE frequency. Pre-treatment SCE frequency was found to be positively correlated with age. Female smokers tended to have higher post-treatment SCE frequencies than male smokers, and pre- and post-treatment SCE frequencies were higher in older males than in older females. Eradication therapy decreased the genotoxicity of H. pylori, but age in males and smoking in females may decrease treatment efficacy.

Otozomal resesif osteopetrozis (ORO) genellikle infant veya çocukluk çağında ölüme yol açan ciddi bir hastalıktır. TNFSF11 geni tarafından kodlanan RANKL ve TNFRSF11A geni tarafından kodlanan RANK proteinleri osteoklast olgunlaşması için önemli olup bu genlerdeki mutasyonların ORO gelişiminde rol oynadığı gösterilmiştir. Bu yazıda aralarında akrabalık bulunan eşlerin 2 çocuğunda da TNFRSF11A geninde c.508 A→G homozigot mutasyonu (pArg170Gly) saptanmış. Bir sonraki gebelik sırasında CVS materyali üzerinde yapılan mutasyon analizinde, fetusta heterozigot mutasyon saptandı. Gebelik terme kadar devam etti ve sağlıklı bir erkek çocuk doğdu. Prenatal mutasyon analizi, mutasyonu bilinen hastalıklarda ebeveynin anksiyetesini rahatlatmak ve aileye genetik danışma vermek için önemlidir. Autosomal recessive osteoporosis (ARO) is a severe disease causing death usually at infancy or childhood. RANKL coded by TNFSF11 gene and RANK coded by TNFRSF11A gene are important proteins for osteoclast maturation and it is indicated that mutation on these genes plays an important role for ARO development. It is reported in this article that c.508 A→G homozygote mutation (pArg170Gly) is observed in TNFRSF11A gene of 2 children of consanguineous couple. Mutation analysis performed on CVS material during the next pregnancy revealed heterozygous mutation in the fetus. The pregnancy was continued to term and a healthy boy was delivered. Prenatal mutation analysis is important for diseases with known mutations to relieve parental anxiety and provide genetic counselling for the family.

Mozaik trizomi 17 nadir görülen otozomal trizomilerden olup literatürde sadece 30 olguda bildirilmiştir. Olguların büyük çoğunluğu “chori onic villus sampling” (CVS) ve amniyosentez materyallerinden yapılan prenatal genetik analizlerde saptanmış olup klinik bulgular son derece değişkendir. Burada sunduğumuz olgunun prenatal dönemde ultrasonografik takibinde lateral ventriküllerde sınırda ventrikülomegali saptandı ve amniyosentez yapıldı. Sitogenetik analiz ile karyotip 47,XX,+17[5]/46,XX[35] olarak saptandı. Yapılan FISH analizi ile mozaik trizomi 17 karyotip bulgusu doğrulandı (nuc ish(RARA×3,PML×2)[30/100], (TP53×3)[35/100]). Termde spontan vajinal yolla doğan olgu nun fizik muayenesinde ve transfontanel ultrasonografisinde herhangi bir dismorfik bulgu ya da konjenital anomali saptanmadı. Periferik kandan postnatal olarak yapılan kromozom analizinde karyotip 46,XX olarak saptandı. Periferik kandan ve yanak mukozasından lokus spesifik problar ile yapılan FISH analizinde de mozaisizm saptanmadı (nuc ish(RARA,PML)×2[200],(TP53×2)[200]). Prenatal tanıda nadir görülen mozaik trizomi 17 saptanan olgumuz, ileride karşılaşılabilecek benzer olgularda ailelere verilecek genetik danışmanlık açısından katkı sağlayacaktır. Mosaic trisomy 17 is rarely observed and about 30 cases have been reported so far. Most of the cases have been identified by genetic diag nostic analysis of chorionic villus sampling (CVS) and amniotic fluid in the prenatal period. Clinical manifestations are extremely variable. In the case presented here, due to the size of lateral ventricles was seen at the upper limit of normal range in the prenatal ultrasonographic investigation, amniocynthesis was performed and the karyotype was found as 47,XX,+17[5]/46,XX[35]. This mosaicism was confirmed by FISH analysis also (nuc ish(RARA×3,PML×2)[30/100],(TP53×3)[35/100]). The baby was born by spontaneous vaginal delivery at term. No dysmorphic feature or congenital anomaly has been observed in the physical examination or in trans-fontanel ultrasonographic examination. Peripheral blood karyotype was found 46,XX. The mosaicism was not diagnosed in FISH analysis of peripheral blood and buccal mucosa samples using spesific probes, too (nuc ish(RARA,PML)×2[200],(TP53×2)[200]). This case report demonstrating uncommon mosaic tri somy 17 would be useful to give genetic counseling to the families having similar cases in the future.

9p delesyon sendromu; trigonosefali, orta yüz hipoplazisi, uzun filtrum, hipertelorizm gibi kraniofasial anomalilerle karakterize, nadir görülen ve iyi tanımlanmış bir sendromdur. Bazı olgularda klinik tabloya genital ve/veya gonadal bozukluklar, kardiyak anomaliler, endokrin ve metabolik bozukluklar eşlik edebilmektedir. Klinik tablonun değişkenlik göstermesi, genetik danışma açısından genotip-fenotip ilişkisinin kesinlik kazanmasını gerektirmektedir. Sunulan 14 aylık kız olgunun aile öyküsünde, opere izole sindaktilisi olan bir erkek kardeş dışında özellik bulunmamaktadır. Olguda, sendromun karakteristik kraniofasial dismorfik bulgularına ek olarak atrial septal defekt, patent foramen ovale, patent duktus arteriozus, pulmoner stenoz, sol ventrikül hipertrofisi ve umbilikal herni gibi konjenital anomaliler bulunmaktadır. Konvansiyonel sitogenetik analizle karyotip özelliği 46,XX,del(9)(p22) olarak saptanan olguda sonuç FISH analizi ile konfirme edilmiştir. Literatür bilgilerine göre olgudaki fenotipik özelliklere, delesyona uğrayan bölgede yer alan CER1, FOXD4, FOXP2 ve DOCK8 genlerinin kaybının neden olduğu düşünülmektedir. As a rare and well defined syndrome, 9p deletion syndrome is characterized with craniofacial abnormalities, such as trigonocephaly, midfa cial hypoplasia, long philtrum and hypertelorism. Some cases also display genital and/or gonadal, as well as cardiac and metabolic abnormal ities. These clinical variations make a necessity for defining genotype-phenotype correlation as genetic counseling. The presented case here is a 14 month-old girl who has a brother with operated syndactyly. She has atrial septal defect, patent foramen ovale, patent ductus arteriosus, pulmonary stenosis and left ventricular hypertrophy and umbilical hernia besides craniofacial abnormalities. Her karyotype was revealed as 46,XX,del(9)(p22) using conventional cytogenetic analysis and confirmed with FISH analysis. According to the recent studies, the deleted part of 9p in this case contains CER1, FOXD4, FOXP2 and DOCK8 genes and it is suggested that the loss of these genes may be the cause of the phenotypic features.

Marker chromosomes are very rare in Klinefelter patients and phenotypic findings are related to the affected chromosomal region. The phenotypic effects of small supernumerary marker chromosomes (sSMC) range from multiple malformations/mental retardation to no effect (le a normal phenotype). This wide spectrum of phenotypes is due to the origin, structure and gene content of the marker chromosome. The first Klinefelter case with sSMC 9 was published by Liehr et al in 2005. The present case was referred for chromosomal analysis because of dysmorphic features, speech delay and mild mental retardation. Conventional cytogenetic analysis revealed the 47 XXY karyotype in 17 metaphases and the 48 XXY + marker karyotype in eight metaphases. Fluorescence in situ hybridization (FISH) analysis to identify the marker chromosome was performed using the LSI p16 (9p21) Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe) and partial trisomy 9 mosaicism was confirmed in this patient. To our knowledge, this is the second case of Klinefelter syndrome with a small supernumerary marker chromosome derived from chromosome 9.

The factors leading to the development of Chronic Myeloid Leukemia (CML) are not fully known. Associations between polymorphisms for genes encoding Glutathione S-transferase (GST) enzymes involved in Phase II detoxification reactions and susceptibility to some cancers have been shown in several studies. The aim of the present study was to investigate the influence of the GSTP1 (IIe105Val) gene polymorphism on human susceptibility to CML. Seventy-one CML patients and 67 control subjects with no cancer history were enrolled in our study . The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the GSTP1 (lle105Val) gene polymorphism. Genotypes were determined according to the bands that formed in agarose gels via gel electrophoresis. Leukocytes in the CML patient group were significantly different from those in the control group (p=0.0001). The frequency of the GSTP1 Val allele was found to be 22% in CML patients and 31% in controls. However, no statistical variation was found to exist between controls and patients in terms of the GSTP1 Val allele frequency (p=0.199). The relationship between the GSTP1 (IIe105Val) gene polymorphism and CML is not fully understood. Our results provide no evidence of a relationship between the GSTP1 (IIe105V al) gene polymorphism and susceptibility to CML in Turkish patients. However, these findings should be confirmed in studies with larger sample sizes.

Polymorphisms in the X-ray repair cross complementing 1 (XRCC1) gene have been found to be associated with susceptibility to various types of cancers. We investigated the association between the XRCC1 gene Arg399Gln polymorphism and the susceptibility to lung cancer in Turkish patients. To determine the association of this polymorphism with the risk of lung cancer in Turkish patients, a hospital-based case-control study was designed, involving 67 patients with lung cancer and 60 control subjects with no cancer history who were matched for age and gender. XRCC1 genotypes (Arg/Arg, Arg/Gln, and Gln/Gln) were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis on genomic DNA. No statistically significant relationship was determined between the lung cancer and control groups (p>0.05). Among the patients, 61% were Arg/Arg, 28% were Arg/Gln, and 11% were Gln/Gln. Among the controls, 50% were Arg/Arg, 38% were Arg/Gln, and 12% were Gln/Gln. There was no difference in the distribution of XRCC1 genotypes or the frequencies of the Arg (75% versus 69%) and Gln (25% versus 31%) alleles between the lung cancer patients and controls. Our results suggest that the XRCC1 gene Arg399Gln polymorphism is not associated with an increased risk for the development of lung cancer in Turkish patients.

Oksidatif stres, tip 1 diyabet (T1D) ve komplikasyonlarının gelişiminde önemli bir rol oynamaktadır Oksidatif stresin zararlı etkilerine karşı savunma sistemlerinden biri de Glutatyon-S-Transferaz (GST)’dır. Çalışmamızda, GSTT1 ve GSTM1 gen polimorfizmleri ile T1D’li Türk hastalar arasındaki ilişkiyi araştırmayı amaçladık. Çalışmamıza, T1D tanısı konmuş 71 hasta ile 62 kontrol birey dahil edildi. GSTM1 ve GSTT1 gen polimorfizmini değerlendirmek için multiplex PCR yöntemi kullanıldı. İstatistiksel analizde anlamlılık düzeyi p 0.05). Bu sonuçlar GSTT1 ve GSTM1 negatif(null) genotiplerinin T1D ve komplikasyonların gelişimi için katkısının olmadığını göstermektedir fakat daha geniş olgu sayılı çalışmalara ihtiyaç vardır. Oxidative stress plays an important role in the development of type 1 diabetes(T1D) and its complications. Glutathione-S-Transferases (GST) is one of the defense systems against the harmful effects of oxidative stress. In our study, we aimed to investigate the relationship between GSTT1 and GSTM1 gene polymorphisms and Turkish patients with T1D. In our study, 71 patients were diagnosed with T1D and 62 control subjects were included. GSTM1 and GSTT1 gene polymorphisms were used to evaluate the multiplex PCR method.In statistical analysis, the level of significance was set at p0.05). These results show that GSTT1 and GSTM1-negative (null) genotypes may not contribute to the development of T1D and its complications but more studies with larger sample size are needed.

Bu çalışmada, dezenfektan ve koruyucu özelliğinden dolayı çok yaygın olarak kullanılan benzalkonyum klorürün genotoksik etkisi in vitro mikronükleus testi ile araştırıldı. Çalışmada, herhangi bir genotoksik ajana maruz kalma öyküsü bulunmayan ve sigara kullanmayan sağlıklı erkek gönüllülerden hazırlanan tam kan lenfosit kültürleri kullanıldı. Kültürlere 6 farklı konsantrasyonda (0.04 mg/L, 0.11 mg/L, 0.33 mg/L, 1 mg/L, 3 mg/L ve 9 mg/L) benzalkonyum klorür ilave edilerek mikronükleus oluşumuna etkisi araştırıldı. Deneyler üç sağlıklı gönüllü ile ve her konsantrasyon için ikişer kültür hazırlanarak çalışıldı. Her kültürden 1000 binükleer hücre değerlendirilerek mikronükleus analizi yapıldı. Negatif kontrol kültürlerinden elde edilen sonuçlar ile yapılan karşılaştırma sonucunda, çalışılan konsantrasyonların hiçbirinde mikronükleus değerlerinde anlamlı artış gözlenmedi. Sonuç olarak uygulanan in vitro kültür koşullarında benzalkonyum klorürün anlamlı genotoksik etkisi tespit edilmedi. In this study, the genotoxic effects of benzalkonium chloride, widely used as a disinfective and protective agent, were investigated using micronucleus assay. Whole blood lymphocyte cultures, prepared from healthy, non-smoking male donors were used in the study. The cultures were treated with 6 different concentrations of benzalkonium chloride (0.04 mg/L, 0.11 mg/L, 0.33 mg/L, 1 mg/L, 3 mg/L, and 9 mg/L) and the effects on micronucleus formation were investigated. Three healthy donors were included in the study and the experiments were done using two cultures for each concentration. Micronuclei were scored examining 1000 binucleated cells for each culture. When compared to negative control, none of the tested concentrations led to a significant increase in micronucleus levels. In conclusion, benzalkonium chloride showed no significant genotoxic effects under our experimental conditions.

Objective: In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationaly exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. Participants: The study included an exposed and two control groups. The exposed group (n = 9) was comprised of oncology nurses. The first (n = 9) and second (n = 10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. Methods: Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. Result: A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. Conclusion: Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.

Fluroscent in situ hybridization analysis indicated presence of t(12;21)(p13;q22) translocation and near-tetraploidy in a case who 11-year-old boy and diagnosed with B precursor acute lymphoblastic leukemia (ALL). Although, some studies suggest good prognostic effect of translocation t(12;21) (p13;q22), there were very little data regarding the prognostic effect of Near-tetraploidy. Here we discussed the prognostic relevance of both t(12;21)(p13;q22) translocation and near tetraplody in Pre-B ALL. Pre- B Akut Lenfoblastik Lösemi tanısı konulan 11 yaşında erkek olguda, Floresans insitu hibridizasyon analizinde t(12;21)(p13;q22) translokasyonu ve near-tetraploidi beraber olduğu gösterilmiştir. Bazı çalışmalarda t(12;21)(p13;q22) trans lokasyonunun iyi prognostik etki oluşturduğu belirtmelerine rağmen near-tetraploidinin prognostik etkisi hakkında çok az bil gi vardır. Burada Pre-B Akut Lenfoblastik Lösemili olguda t(12;21)(p13;q22) translokasyonu ile birlikte near tetraplodi bulgu larının birlikte etkisi tartışılmaktadır.

Objective Nonsyndromic autosomal recessively inherited non-goitrous congenital hypothyroidism (CHNG) can be caused by mutations in TSHR, PAX8, TSHB and NKX2-5. We aimed to investigate mutational frequencies of these genes and genotype/phenotype correlations in consanguineous families with CHNG. Design Because consanguinity in individuals with a presumptive genetic condition is often an indicator of an autosomal recessive inheritance and allows firmer correlations to be established between genotype and phenotype, we planned to execute our study in consanguineous families. Patients Hundred and thirty-nine children with CHNG phenotype born to consanguineous families. Measurements First, we investigated cases for evidence of linkage to the four known CHNG genes by microsatellite marker analysis. Mutation analysis by direct sequencing was then performed in those cases in whom linkage to the relevant candidate gene could not be excluded. In addition, in silico analysis of the predicted structural effects of TSHR mutations was performed and related to the mutation-specific disease phenotype. Results Homozygous germline TSHR mutations were detected in six families (5%), but no mutations were detected in PAX8, TSHB and NKX2-5. Four of TSHR mutations had not previously been described. Genotype-phenotype correlations were established and found to be related to the predicted structural effects of the mutations. Conclusions Known causative genes account for the development of CHNG only in a minority of cases, and our cohort should provide a powerful resource to identify novel causative genes and to delineate the extent of locus heterogeneity in autosomal recessively inherited CHNG. NewLife WellChild Wellcome Trust European Commission European Commission Pasteur Foundation of New York

2008 yılında Uluslararası katılımlı VIII. Ulusal Tıbbi Genetik Kongresinde yazılı bildiri olarak sunulmuştur. Bu çalışmada, 2004-2008 yılları arasında prenatal tanı amacı ile gelen 200 hastanın konvansiyonel sitogenetik ve FISH analiz sonuçları sayısal kromozomal anomaliler yönünden endikasyonlarına göre; anormal ultrason bulgusu (AUS), üçlü tarama testi riski (ÜTT), ileri maternal yaş (İMY) ve diğerleri olarak dört ana grupta ve ek endikasyonlara göre de alt gruplarda değerlendirildi. Değerlendirilen 200 vaka içinde, 52 vaka ileri maternal yaş, 59 vaka anormal ultrason bulgusu, 44 vaka üçlü tarama test riski nedeniyle gönderilmişti. Diğer endikasyonlarla gelen vakaların sayısı ise 11 olarak tespit edildi. AUS ile gelen vakalarda sayısal kromozomal anomali oranı AUS içermeyen vakalara göre daha yüksek bulundu (p=0.002). AUS olan ve özellikle geç dönemde amniyosentez yapılan olgularda, konvansiyonel sitogenetik analize ek olarak FISH gibi hızlı sonuç alınan yöntemlerin uygulanmasının sonuç verme süresinin kısaltılabilmesi, olası terminasyonun erkene alınması, annenin bekleme stresinin azaltılması, ilave tetkik yapılacaksa zaman kazanılması gibi önemli yararlar sağlaması nedeniyle oldukça etkili ve gerekli olduğu gözlendi. In this study, the results of conventional cytogenetic and FISH analysis of 200 cases who were admitted for prenatal diagnosis in 2004-2008 were grouped and evaluated according to the indications as abnormal ultrasound findings, triple test risk, advanced maternal age and the others. Subgroups were designated according to the additional indications. In evaluated 200 cases, 52 cases referred for advanced maternal age, 59 cases for abnormal ultrasound findings, 44 cases for triple test risk, 11 cases for other indications. Numerical chromosomal aberration ratio was observed higher in the group with abnormal ultrasound findings than the other groups without abnormal ultrasound findings (p=0.002). In prenatal diagnosis, application of the rapid assays such as FISH is very important and necessary especially in cases who have late amniocentesis and abnormal ultrasound findings because of shortening the result giving time, taking possible termination time earlier, decreasing mother’s waiting stress, saving time for additional tests.

Angiotensin-converting enzyme (ACE) is a vital enzyme in the renin-angiotensin-aldosterone system, and there are reports in the literature describing its role in the development of cardiovascular system diseases, with I/D polymorphism of the ACE gene. We examined the relationship between a patient group with obstructive sleep apnea syndrome (OSAS) and a control group in terms of I/D polymorphism of the ACE gene. We examined 64 patients, with 37 individuals serving as the control group. PCR was used to detect ACE I/D gene polymorphism. Genotype was determined according to the bands that formed on agarose gel electrophoresis. Among the 64 OSAS patients, 27 were identified with the ID genotype, 27 with the DD genotype and 10 with the II genotype; among the 37 control subjects, 19 were identified with the ID genotype, 11 with the DD genotype and 7 with the II genotype. When the case group and controls were compared in terms of ID, II and DD genotypes, no significant difference was observed. On the other hand, when the two groups were compared with respect to mean body mass index, the OSAS group was found to be significantly different from the control group (P = 0.009). We conclude that ACE I/D gene polymorphism is not a genetic risk factor for OSAS in Turkish patients.

We report a case of childhood acute lymphoblastic leukemia (ALL) with both acute myeloid leukemia 1 (AML1) amplification and 17q25 deletion. AML1 gene is located on 21q22 and encodes a transcription factor. AML1 amplification is a common finding in childhood ALL, and itis observed as an increase in gene copy number by the FISH analysis. The mechanism of AML1 amplification is not associated with AML1 gene mutations. The 17q25 is a gene-rich chromosomal location and distinct abnormalities of this region have been observed in previous cases of different kinds of leukemia. Deletion of the 17q25 region has been reported in two leukemia patients. Septin 9 (SEPT9) and survivin genes are located on 17q25. High expression of these genes and AML1 amplification are regarded as markers in tumorigenesis and disease progression; however, more data are needed for accurate prognostic evaluation. J. Clin. Lab. Anal. 23:368–371, 2009. © 2009 Wiley-Liss, Inc.

The development of imatinib as a therapeutic agent targeting BCR-ABL has increased the treatment options for chronic myeloid leukemia (CML) by significantly impacting outcomes, and imatinib is recommended by treatment guidelines as the first-line therapy. However, treatment of maternal CML with imatinib during gestation is not recommended because of the potential risk to the fetus. We describe the clinical presentation, course and outcome of one pregnant patient with CML who was treated with imatinib. We review all pregnancies associated with imatinib documented in the literature. A 27-year-old pregnant patient was diagnosed to have Philadelphia chromosome positive chronic phase CML in August 2007. Imatinib was administered (400 mg/day) between the 21st and 39th weeks of gestation. The patient tolerated the drug well and achieved complete hematological and cytogenetic remission. There were no imatinib-related maternal complications during the pregnancy. Fetal growth remained normal as well as amniotic fluid volume estimation. Labor was induced at the 39th gestational week, resulting in the uneventful vaginal delivery of a healthy male infant without any congenital anomaly. Umbilical cord blood and infant peripheral blood were collected at delivery. No postnatal complications occurred; however, imatinib was present in the umbilical cord blood (338 ng/mL) and in the infant's peripheral blood (478 ng/mL). Breast milk was collected on different postpartum days, and concentrations of imatinib were detected. At 10 months of age, the baby had normal growth and development. In light of reported cases and our experience, treatment of CML during the second and third trimesters of gestation and breast feeding seems to be safe, but the data are still limited and the effects of chronic exposure of infants to imatinib are not known. We think that each case should be examined and considered independently, and decisions should be individualized. Novartis Pharmaceutical Corporation

It is well established that testicular differentiation of the human embryonic gonad depends on the action of the Y-chromosomal gene SRY. However, exceptional cases such as SRY-negative cases of 46,XX testicular disorder of sexual development (DSD), and of 46,XX ovotesticular DSD document that testicular tissue can develop in the absence of the SRY gene. These SRY-negative XX sex reversal cases are very rare and usually sporadic, but a few familial cases have been reported. We present a large, consanguineous family with nine affected individuals with phenotypes ranging from 46, XX testicular DSD to 46, XX ovotesticular DSD, with predominance of male characteristics. Absence of SRY in peripheral blood was documented by fluorescence in situ hybridization (FISH) and PCR analysis in all nine affected individuals, and by FISH analysis on gonadal sections with testicular tissue in four affected individuals. By quantitative PCR, a duplication of the SOX9 gene was excluded. In addition, as linkage analysis showed that the nine affected members of the family do not share a common SOX9 haplotype, any mutation at the SOX9 locus could be ruled out. Together, these findings implicate a mutation at a sex-determining locus other than SRY and SOX9 as the cause for the XX sex reversal trait in this family.

Background: Black tea is known to have protective effects against plasma lipid and lipoprotein oxidation, but its influence on lipid peroxidation in tissue has been less studied. The effect of oral black tea consumption on protein oxidation has also not been demonstrated. The present study investigated the antioxidant effects of oral black tea consumption. Material/Methods: Male Sprague-Dawley rats were fed a regular murine chow diet. The controls were supplied With water ad libitum, while the black tea group received aqueous black tea extract as the sole source of liquids. At the end of the ten-week experimental period, intestinal brush border, liver and kidney reduced-glutathione concentrations were evaluated as an index of cellular antioxidant defence. Plasma and tissue malondialdehyde concentrations and plasma protein carbonyl content were measured to evaluate lipid peroxidation and protein oxidation, respectively. Results: The plasma malondialclehyde and protein carbonyl contents of rats consuming the black tea were significantly less than in controls. Similarly, liver and kidney malondialdehyde concentrations were significantly lower in the experimental group, while jejunoileal mucosa were not affected. Ten weeks of black tea administration caused significantly higher reduced-glutathione levels in the kidneys of black tea-administered rats, and a significant negative correlation was observed between kidney malondialdehyde and glutathione concentrations. Conclusions: These findings provide evidence that long term black tea supplementation is capable of protecting both plasma proteins and plasma lipids from oxidative injury, and demonstrate that chronic black tea administration protects both liver and kidney tissues - but not the jejunoileal mucosa against oxidation.

Dünyada ve Türkiye'de koyun ve koyun ürünleri ekonomik bakımdan büyük değer taşır.Bu nedenle koyun yetiştiriciliğinde hayvan ıslahının temel ilkesi olan hayvan başına verim düzeyinin yükseltilmesi amaçlanır. Damızlığa ayrılan hayvanlar arasında üstün verimli hayvan oranının fazla olması döl veriminin yüksek olması ile mümkündür. Dünya genelinde bulunan koyun populasyonlarında 1980 yılından itibaren dölverimi ile ilişkili major genlerin kalıtım özellikleri ve DNA testleri uygulanarak yapılan çalışmalarda, major genlerin döl verimi performansını önemli ölçüde artırma potansiyeline sahip olduğu görülmüştür.Yapılan çalışmalarda BMPR-IB, BMP-15 ve GDF-9 genlerinde bulunan mutasyonların koyunlarda ovulasyon oranını artırarak döl verimi üzerinde etkili olduğu gösterilmiştir.Özellikle 6. kromozom üzerindeki BMPR-IB geninde bulunan ve Booroola Merinosunda FecB allelinin oluşmasına yol açan mutasyonun belirlenmesi ile ebeveyn kayıtlarına ihtiyaç duyulmadan %100 doğru sonuç veren DNA testinin geliştirilmiş olması bu mutasyonun diğer ırklarda da araştırılmasına olanak sağlamıştır.Çoklu doğum özelliği olan ve Türkiye'de yetiştirilen Sakız koyun BMPR-IB genindeki Fec B allelinin PCR-RFLP yardımıyla aranmasının amaçlandığı bu çalışmada Türkiye'de çeşitli yerlerde (Bandırma, İzmir-Çeşme ve Urla, Çanakkale-Ayvacık ) yetiştirilen 388 adet Sakız ve 18 adet Sakız-Kıvırcık melezi koyundan toplam 406 adet kan örneği EDTA'lı tüplere alınmıştır. Fenol/kloroform yöntemi ile DNA izolasyonu yapılan örneklerden Polimeraz Zincir Reaksiyonu (Polymerase Chain Reaction: PCR) yöntemiyle Test F2 veTest R15 primerleri kullanılarak DNA amplifikasyonları gerçekleştirilmiştir. Agaroz jelelektroforezi kullanılarak görüntülenen PCR ürünlerine daha sonra Ava II restriksiyon enzimiile kesim yapılmıştır. Sonuç olarak incelenen 406 baş koyunda BMPR-IB geninde FecB alleli belirlenememiştir. Both worldwide and in Turkey sheep breeding and sheep products are of great economicvalue. For this reason the main principle in sheep breeding is to increase efficiency rate persheep. An increase in among the sheep breeds for breeding is closely related to the litter size.Research conducted since 1980 in relation to inheritance patterns and DNA testing of majorgenes for prolificacy has shown that major genes have the potential to significantly increasethe reproductive performance of sheep flocks throughout the world. Mutations that increaseovulation rate have been discovered in the BMPR-1B, BMP-15 and GDF-9 genes. Thediscovery of the Fec B allele in BMPR-IB gene on sheep chromosome 6 of the BooroolaMerino enabled a DNA test to be developed that is 100% accurate and requires no parentalinformation. The availability of the new accurate test without the need for parentalinformation has provided to test this mutation in other sheep breeds.In this study, the availability of previously identified Fec B allele in BMPR-IB geneinfluencing prolificacy is investigated in the highly prolific Chios sheep breed in Turkey byPCR-PFLP. A total of 406 sheep blood samples, 388 samples from the different Chios sheeppopulations (Bandırma, İzmir-Çeşme and Urla, Çanakkale-Ayvacık) and 18 samples ofChios X Kivircik sheep from Yenice, were collected in EDTA containing tubes. The DNA swere extracted by standard phenol/chloroform method and amplified by Polymerase ChainReaction (PCR) using the appropriate primers Test F2 and Test R15. The PCR products wereimaged using agarose gel electrophoresis. None of the 406 sheep carried the Fec B allele ofBMPR-IB gene. Ayvacık Tarım İlçe Müdürlüğü

SAKIZ KOYUN IRKINDA BMPR-IB GEN NDEÇOKLU DOĞUMA NEDEN OLAB LECEK FEC B ALLEL VARLIĞININPCR-RFLP YÖNTEM LE ARAŞTIRILMASIYasemin ÖZEN POLATDanışman: Yrd.Doç.Dr. Tuna GÜLTENÖZETDünyada ve Türkiye'de koyun ve koyun ürünleri ekonomik bakımdan büyük değer taşır.Bu nedenle koyun yetiştiriciliğinde hayvan ıslahının temel ilkesi olan hayvan başına verimdüzeyinin yükseltilmesi amaçlanır. Damızlığa ayrılan hayvanlar arasında üstün verimlihayvan oranının fazla olması dölveriminin yüksek olması ile mümkündür. Dünya genelindebulunan koyun populasyonlarında 1980 yılından itibaren dölverimi ile ilişkili major genlerinkalıtım özellikleri ve DNA testleri uygulanarak yapılan çalışmalarda, major genlerindölverimi performansını önemli ölçüde artırma potansiyeline sahip olduğu görülmüştür.Yapılan çalışmalarda BMPR-IB, BMP-15 ve GDF-9 genlerinde bulunan mutasyonlarınkoyunlarda ovulasyon oranını artırarak dölverimi üzerinde etkili olduğu gösterilmiştir.Özellikle 6. kromozom üzerindeki BMPR-IB geninde bulunan ve Booroola Merinosunda FecB allelinin oluşmasına yol açan mutasyonun belirlenmesi ile ebeveyn kayıtlarına ihtiyaçduyulmadan %100 doğru sonuç veren DNA testinin geliştirilmiş olması bu mutasyonun diğerırklarda da araştırılmasına olanak sağlamıştır.Çoklu doğum özelliği olan ve Türkiye'de yetiştirilen Sakız koyun BMPR-IB genindekiFec B allelinin PCR-RFLP yardımıyla aranmasının amaçlandığı bu çalışmada Türkiye'deçeşitli yelerde (Bandırma, zmir-Çeşme ve Urla, Çanakkale-Ayvacık ) yetiştirilen 388 adetSakız ve 18 adet Sakız-Kıvırcık melezi koyundan toplam 406 adet kan örneği EDTA'lıtüplere alınmıştır. Fenol/kloroform yöntemi ile DNA izolasyonu yapılan örneklerdenPolimeraz Zincir Reaksiyonu (Polymerase Chain Reaction: PCR) yöntemiyle Test F2 veTest R15 primerleri kullanılarak DNA amplifikasyonları gerçekleştirilmiştir. Agaroz jelelektroforezi kullanılarak görüntülenen PCR ürünlerine daha sonra Ava II restriksiyon enzimiile kesim yapılmıştır. Sonuç olarak incelenen 406 baş koyunda BMPR-IB geninde FecB allelibelirlenememiştir.Sakız koyunu / BMPR-IB geni / Fec B alleli / çoklu doğum INVESTIGATION OF THE Fec B ALLELE IN BMPR-IB GENE INFLUENCINGPROLIFICACY IN CHIOS SHEEP BREED BY PCR-PFLPYasemin ÖZEN POLATSupervisor: Asist. Prof. Dr. Tuna GULTENSUMMARYBoth worldwide and in Turkey sheep breeding and sheep products are of great economicvalue. For this reason the main principle in sheep breeding is to increase efficiency rate persheep. An increase in among the sheep breeds for breeding is closely related to the litter size.Research conducted since 1980 in relation to inheritance patterns and DNA testing of majorgenes for prolificacy has shown that major genes have the potential to significantly increasethe reproductive performance of sheep flocks throughout the world. Mutations that increaseovulation rate have been discovered in the BMPR-1B, BMP-15 and GDF-9 genes. Thediscovery of the Fec B allele in BMPR-IB gene on sheep chromosome 6 of the BooroolaMerino enabled a DNA test to be developed that is 100% accurate and requires no parentalinformation. The availability of the new accurate test without the need for parentalinformation has provided to test this mutation in other sheep breeds.In this study, the availability of previously identified Fec B allele in BMPR-IB geneinfluencing prolificacy is investigated in the highly prolific Chios sheep breed in Turkey byPCR-PFLP. A total of 406 sheep blood samples, 388 samples from the different Chios sheeppopulations (Bandırma, zmir-Çeşme and Urla, Çanakkale-Ayvacık) and 18 samples ofChios X Kivircik sheep from Yenice, were collected in EDTA containing tubes. The DNA?swere extracted by standard phenol/chloroform method and amplified by Polymerase ChainReaction (PCR) using the appropriate primers Test F2 and Test R15. The PCR products wereimaged using agarose gel electrophoresis. None of the 406 sheep carried the Fec B allele ofBMPR-IB gene.Chios sheep / BMPR-IB gene / Fec B allele / prolificacy 55

Because of the teratogenicity data in rats, it is recommended that women treated with imatinib should be aware of the potential teratogenicity of imatimb and effective contraception should be used during imatinib therapy to prevent pregnancy. We describe successful pregnancy and delivery, without any congenital anomaly, in a patient with CML under treatment of imatinib. The fetus had been exposed to imatinib for 8 weeks. The patient remained off treatment during gestation and cytogenetic relapse of CML (5 months after discontinuation of imatinib therapy) developed at seventh month of gestation. (c) 2005 Elsevier Ltd. All rights reserved.

Kromozomal sayısal düzensizlikler ve translokasyonlar genelde çocukluk çağı lösemilerinin başlangıcındaki olaylardır, yada hastalığın oluşmasını sağlayan ilk olaylardır. Çocukluk çağı lösemilerine özgü spesifik genetik değişiklikler, hastalığın tanısı ve tedaviye yanıtın izlenmesi açısından oldukça önemlidir. Bu genetik değişiklikler aynı zamanda hastalığın prognozu açısından da önemli bir gösterge oluşturmaktadır. Böylece, bu spesifik genetik değişikliklerin tespiti ve sınıflandırılması klinisyenlere hastalığın tanısı, tedavisi, prognozunun takibi ve yeni terapötik yaklaşımların uygulanması açısından yardımcı olacaktır. Chromosomal numerical aberrations and translocations are often the first or initiating events in childhood leukemias. The specific genetic changes in childhood leukemias are important to diagnose the disease and to monitor the response to the treatment. Furthermore, these kind of genetic alterations form an important indicator for the prognosis of the diseases. Therefore, the detection and the genetic classification of these specific genetic alterations in childhood leukemias would help clinicians for the diagnosis, treatment, and monitoring the prognosis of the disease as well as applying novel therapeutic approaches.

We present the case of the childhood ALL that was identified by the translocation of the ABL1 gene to the q21 band of chromosome 2 without t(9;22)(q34;q11) translocation. The observation of a poor clinical course of the case may contribute to explanation of the action of t(9;22)(q34;q11) translocation, of which poor prognostic action is known on ALL's, in terms of ABL1 gene, independent of the BCR gene. On the other hand, the prognostic significance of this variant ABL1 translocation detection, which is very rarely observed, will cast a light on future cases (Tab. 1, Fig. 1, Ref. 11). Full Text in free PDF www.bmj.sk.