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Background Anti-neoplastic agents are widely used in the treatment of cancer and some non-neoplastic diseases. These drugs have been proved to be carcinogens, teratogens, and mutagens. Concern exists regarding the possible dangers of the staff handling anti-cancer drugs. The long-term exposure of nurses to anti-neoplastic drugs is still a controversial issue. The purpose of this study was to monitor cellular toxicity parameters and gene expression in nurses who work in chemotherapy wards and compare them to nurses who work in other wards. Methods To analyze the apoptosis-related genes overexpression and cytotoxicity effects, peripheral blood lymphocytes obtained from oncology nurses and the control group. The results Significant alterations in four analyzed apoptosis-related genes were observed in oncology nurses. In most individual samples being excavated, Bcl-2 overexpression is superior to that of Bax. Prominent P53 and Hif-1α up-regulation were observed in oncology nurses. Moreover, all cytotoxicity parameters (cell viability, ROS formation, MMP collapse, Lysosomal membrane damage, Lipid peroxidation, Caspase 3 activity and Apoptosis phenotype) in exposed oncology nurses were significantly (p Conclusion Our data show that oxidative stress and mitochondrial toxicity induced by anti-neoplastic drugs lead to overexpression of apoptosis-related genes in oncology nurses.

Idiopathic renal hypouricemia is a rare hereditary condition. Type 2 renal hyperuricemia (RHUC2) is caused by a mutation in the SLC2A9 gene, which encodes a high-capacity glucose and urate transporter, glucose transporter (GLUT)9. RHUC2 predisposes to exercise-induced acute renal failure (EIARF) and nephrolithiasis, which is caused by a defect in renal tubular urate transport and is characterized by increased clearance of renal uric acid. In the present study a case of a 35-year-old Chinese man with EIARF is reported. The patient had isolated renal hypouricemia, with a serum uric acid level of 21 µmol/l and a fractional excretion of uric acid of 200%. The mutational analysis revealed a homozygous mutation (c.857G>A in exon 8) in the SLC2A9 gene. The patient's family members carried the same mutation, but were heterozygous and clinically asymptomatic. In conclusion, to the best of our knowledge, this is the first report of a RHUC2 patient with a GLUT9 mutation, p.W286X, which may be a pathogenic mutation of RHUC2. Further investigation into the functional role of GLUT9 in this novel SLC2A9 mutation is required.

Diallyl disulfide (DADS) is one of the primary components of garlic and it exhibits a broad range of biological activities. In the present study, the effects of DADS on lipid metabolism and its potential role in the modulation of the gut microbiome were determined. Hematoxylin and eosin and oil-red O staining were used to assess the liver and intestinal tissues of mice treated with DADS. The expression of lipid metabolism-associated genes was measured using reverse transcription-quantitative PCR (RT-qPCR). The effects of DADS on the gut microbiome were measured using 16S recombinant (r)DNA gene analysis. The results revealed that the serum non-esterified free fatty acids, high density lipopro-tein-cholesterol, low density lipoprotein-cholesterol, serum total cholesterol, liver triglyceride and total cholesterol levels of the mice fed with a low-dose of DADS was significantly higher when compared with the control. Hematoxylin and eosin and oil-red O staining demonstrated that DADS induced fatty liver in mice. The results of the RT-qPCR revealed that the expression levels of a number of lipid metabolism-associated genes were altered in the livers of mice treated with DADS. The 16S rDNA gene analysis demonstrated that the mice fed on a normal diet treated with a low-dose of DADS had decreased levels of bacteria from the Bacteroidetes phyla and increased levels of bacteria from the Firmicutes phyla. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the top 20 pathways enriched in the low-dose DADS group of mice fed with a normal diet. In the present study, low-dose DADS induced fatty liver and altered the gut micro-biota, similar to the phenotype induced by a high fat diet, by regulating the expression of lipid metabolism associated genes.

İnsan geni üzerindeki incelemeler, genlerin ve gen ürünlerinin incelenmesini içerir. Bu incelemelerin insanlığa bir çok alanda olumlu katkılar sağladığı açıktır. Ancak gen incelemeler, etik ve hukuksal açıdan çeşitli sorunlara yol açmıştır. Oluşan bu sorunlara hukuk, etik, biyoetik ve tıp biliminin kurallarıyla, etik ilkelere uygun çözümler getirilmeye çalışılmıştır.Ülkemizde gen incelemelerinin yapılışını ve sonuçlarını düzenleyen bağımsız bir yasal düzenleme bulunmamaktadır. Konuya ilişkin Avrupa Biyotıp Sözleşmesi, AİHS gibi iç hukukumuzu bağlayıcı sözleşmelerin yanı sıra, bildirge ve yönergeler ile Anayasamız, TMK, TBK, Kişisel Verilerin Korunması Kanunu, Hukuk Muhakemeleri Kanunu gibi ulusal yasalarımız ile Türk Deontoloji Nizamnamesi ve ÜYTE, HHY gibi yönetmeliklerle, insan geni üzerindeki incelemelerin sebep olduğu etik ve hukuksal sorunlar çözümlenmeye çalışılmaktadır. Bu nedenle genetik incelemeler ve tanılarla ilgili olarak , Gen Teşhisi Kanunu, Embriyonun Korunması Kanunu, Kök Hücre Araştırmaları Kanunu gibi kanunların bir an önce çıkarılması zorunludur. Hatta bu konuların tümünün İnsan Geni İncelemeleri Hakkında Kanun olarak düzenlenmesi isabetli olacaktır. Bu yasa ile insan haklarının ve temel özgürlüklerin ve insan onuruna saygının korunması gerçekleşecektir. İnsan geni üzerinde yapılacak incelemeler ile bu incelemelerin sonuçlarının etik ilkeler de göz önüne alınarak; ulusumuzun hak ettiği demokratik, çağcıl, insan onuruna ve haklarına uyan yasal düzenlemelerin, Avrupa Biyotıp Sözleşmesi başta olmak üzere evrensel hukuk normlara uygun olarak bir an önce gerçekleştirilmesi kaçınılmaz bir zorunluluktur. The research on human genes includes the research of genes and gene products. It is apparent that these researches are beneficial to human beings on multiple fields. However, research on genes has caused problems from an ethical and legal perspective. Solutions for these problems are tried to be given with legal, ethical, bioethical and medical rules and ethical principles. There is no independent legal arrangement that regulates the process of genetic research and the results thereof that are carried out in our country. We try to resolve ethical and legal problems that occur due to the research on human genes with the help of conventions that are internally binding such as the European Biomedical Agreement and the European Human Rights Convention, on the other hand we use instructions and directives and national laws, such as the Constitution, the Turkish Civil Code, the Turkish Code of Obligations, the Law On The Protection Of Personal Data and the Civil Procedure Code, but also regulations such as the Turkish Deontology Charter, the Regulation on Centres of Reproductive Support and the Patients' Rights Charter. Therefore laws governing genetic research and diagnoses, such as the Genetic Diagnosis Code, the Protection of the Embryo Code, the Research of Stem cells code should be drafted immediately. It might be even good to address all of these issues in one Research on Human Genes Code. With this law, the protection of human rights and fundamental freedoms, as well as the respect for human dignity can be ensured. It is necessary to draft democratic, contemporary legal regulations that are in accordance with human dignity and human rights, which are also in accordance with the European Biomedical Agreement and other international legal norms, as soon as possible while taking into account the research on human genes as well as the results thereof in light of ethical principles. 323

Amaç: Akciğer kanseri tüm dünyada insidans ve mortalite oranları bakımından bütün kanserler arasında ilk sırada yer alır ve sağkalım süresi, tedaviye yanıtın düşüklüğü gibi sebeplerle bireye özgü takip gerektirmektedir. Hastanın genetik bilgileri ışığında tedaviye olası yanıtın değerlendirilmesi hastalar için oldukça önemlidir. Bu çalışma ile akciğer kanseri hastalarında tanı ve tedavide büyük önem taşıyan moleküler hedeflerin ve buna bağlı olarak hedefleyici tedavilerin solid biyopsi ve likit biyopsi yöntemleri ile araştırılması ve her iki yöntemin etkinliğinin ortaya konulması amaçlanmıştır.Yöntem: Çalışmamızda akciğer kanseri tanılı 30 hastada Likit Biyopsi (LB) testi kapsamında Yeni Nesil Dizi Analizi (NGS) yöntemiyle 11 gen taranmış ve analiz edilmiştir. Aynı hasta grubundan çeşitli girişimsel işlemler ile elde edilmiş biyopsi materyallerinde saptanan mutasyon verileri hasta dosyalarından temin edilmiştir. Belirlenen mutasyonların sıklığı ve varlığı üzerinden her iki yöntem araştırılmıştır. Bulgular: NGS tabanlı Likit Biyopsi testi kapsamında hastaların EGFR, TP53, PIK3CA, MET, MAP2K1, ALK, KRAS, BRAF ve NRAS genlerinde çeşitli varyasyonlar saptanmıştır. Saptanan bazı varyasyonlar ilaçlarla ilişkilendirilmiştir. Solid biyopsi materyali ile yapılan çalışmalara ait veriler değerlendirilmiş, hastaların EGFR ve ROS1 genlerinde mutasyona rastlandığı kaydedilirken, solid biyopsi materyaliyle çalışma yapılan hiçbir hastada ALK geninde mutasyon gözlenmemiştir. Sonuç: Likit biyopsi çalışmaları günümüzde altın standart olarak kabul edilen solid biyopsiye alternatif oluşturmakta ve tümör genotipindeki değişikliklerin güncel durumunun izlenmesinde hasta bireylere avantaj sağlamaktadır. Yapılan çalışmanın sonucunda solid biyopsi ve likit biyopsi yöntemleri ile araştırılan mutasyonlar arasında bir uyum olduğu gözlenmiş olup hedef gen paneli analizlerinin tedavide hedefe yönelik ilaç önermede oldukça etkili bir yöntem olduğu tespit edilmiştir.Anahtar Kelimeler: akciğer kanseri, solid biyopsi, likit biyopsi, gen Objective: Lung cancer is the first stage among all cancers in terms of incidence and mortality rates all over the world. It is a disease that requires routine and individual follow-up due to reasons such as survival time, low response to treatment. Evaluation of the possible response to treatment in the light of the patient's genetic information is very important for patients. The aim of this study is to investigate the molecular targets that are of great importance in the diagnosis and treatment of lung cancer patients and accordingly the targeted therapies with solid biopsy and liquid biopsy methods and to reveal the effectiveness of both methods.Method: In our study, 11 genes were screened and analyzed with the new generation sequence analysis method in 30 patients with lung cancer. The mutation data obtained from the biopsy materials obtained by various interventional procedures of the same patient group were obtained from the patient files. The frequency and presence of the identified mutations were investigated in both methods.Results: Various variations of EGFR, TP53, PIK3CA, MET, MAP2K1, ALK, KRAS, BRAF and NRAS genes have been determined in the scope of NGS based Liquid Biopsy test. Some variations have been associated with drugs. Data on solid biopsy materials were evaluated and mutations were observed in EGFR and ROS1 genes. No mutation was observed in ALK gene in any patient with solid biopsy material.Conclusion: Liquid biopsy studies are an alternative to solid biopsy which is accepted as the gold standard and it provides an advantage to patient individuals in monitoring the current status of changes in tumor genotype. As a result of the study, it was observed that there was a correlation between Solid Biopsy and Liquid Biopsy methods and the target gene panel analyzes were found to be a highly effective methodin the treatment of targeted drugs.Keywords: lung cancer, solid biopsy, liquid biopsy, gene 81

Bu çalışmada, Diyarbakır yöresindeki Kıl keçilerinin filogenetik yapıları moleküler tekniklerle belirlenmeye çalışılmıştır. Araştırmanın hayvan materyalini, Diyarbakır yöresinde yetiştirilen Kıl keçileri oluşturmuştur. Kıl keçilerinde D-loop bölgesi dizisine göre; toplam bölge sayısı, G+C oranı, polimorfik bölge sayısı, haplotip sayısı, haplotip farklılığı ve nükleotid farklılığı değerleri sırasıyla, 481, 0.378, 37, 20, 1.000±0.0016, ve 0.01601±0.00006 olarak bulunmuştur. Kıl keçisi haplotipleri arasında genetik uzaklıklar 0.002-0.034 arasında hesaplanmıştır. Bu çalışmadaki keçi haplotiplerin Dloop dizileri ve referans dizi (A, B, C, D, F ve G soyları için) ile birlikte oluşturulan Neighbor-Joining (N-J) filogenetik ağaçta, 20 haplotip A soyunda yer almıştır. In this research, determination of phylogenetic tree of goats in Diyarbakır province using molecular techniques was the main goal. Hair goats raised in Diyarbakır province were used as the animal materials. In Hair goats, base on D-loop sequence; the number of DNA sequence, G + C ratio, polymorphic region number, the number of haplotypes, haplotype diversity and nucleotide diversity were calculated as 481, 0.378, 37, 20, 1.000±0.016, and 0.01601±0.00006, respectively. The genetic distance was calculated as 0.002-0.034 between haplotypes. Neighbor-Joining (N-J) phylogenetic tree formed in this research using goat haplotype D-loop sequences and reference sequences (for A, B, C, D, F and G lineages), 20 haplotypes were in A lineage. 67

Behçet hastalığı (BH), etiyolojisi bilinmeyen, tekrarlayan inflamatuar ataklar ile seyreden, artmış sitokin cevabına neden olan inflamatuar bir hastalıktır.2010 yılında Remmers ve arkadaşlarının Türk toplumundaki Behçet hastalarında yürüttüğü GWAS çalışmasının sonuçlarına göre; IL23R-IL12RB2 lokusunda rs924080 SNP'leri BH ile ilişkili varyantlar olarak tespit edilmiştir (P

Oguchi disease is a rare form of congenital stationary night blindness with an autosomal recessive inheritance pattern. The presence of S‑antigen (SAG) and G‑protein‑dependent receptor kinase 1 (GRK1) mutations were investigated in the family members with Oguchi disease. All exons of the SAG and GRK1 genes were amplified by polymerase chain reaction and sequenced. The patients were shown to have characteristic clinical features of Oguchi disease. Gene analysis determined a novel GRK1 mutation c.923T>C, which caused Oguchi disease in all siblings. This mutation, was demonstrated by amino acid alignment analysis to be in a phylogenetically conserved region and resulted in an amino acid change from leucine to proline at position 308. Thus, the present study reports a novel missense mutation of GRK1 in the affected members of a consanguineous Turkish family. Homozygosity at position 308, which resides in the catalytic domain of the GRK1 gene, is the cause of Oguchi disease in this Turkish family.

In many diseases classification an accurate gene analysis is needed, for which selection of most informative genes is very important and it require a technique of decision in complex context of ambiguity. The traditional methods include for selecting most significant gene includes some of the statistical analysis namely 2-Sample-T-test (2STT), Entropy, Signal to Noise Ratio (SNR). This paper evaluates gene selection and classification on the basis of accurate gene selection using structured complex decision technique (SCDT) and classifies it using fuzzy cluster based nearest neighborclassifier (FC-NNC). The effectiveness of the proposed SCDT and FC-NNC is evaluated for leave one out cross validation metric(LOOCV) along with sensitivity, specificity, precision and F1-score with four different classifiers namely 1) Radial Basis Function (RBF), 2) Multi-layer perception(MLP), 3) Feed Forward(FF) and 4) Support vector machine(SVM) for three different datasets of DLBCL, Leukemia and Prostate tumor. The proposed SCDT &FC-NNC exhibits superior result for being considered more accurate decision mechanism.

Rationale: Medullary thyroid carcinoma (MTC) is an aggressive subtype of thyroid cancer with frequent hematogenous metastasis. While its metastasis is usually observed in the lung, liver, or bone, it rarely migrates to the breast. Patient concerns: Here we report 2 cases with a complaint of breast lump after initial treatment of MTC. Diagnoses: In both patients, the MTC characteristics of breast nodules were confirmed by pathologic analysis of biopsy specimens. Interventions: The genetic mutations within the metastatic breast lesion were evaluated. Wide local excision was thus performed to 1st case, while no therapeutic intervention for another patient due to the wide-spread presence of the disease. Outcomes: No sign of relapse or metastasis was found in 1st case during a 14-month follow-up. For 2nd case, the breast nodule grew to 14 mm within 3 months before remaining stable for 10 months. Lessons: MTC can be a very indolent disease despite its aggressiveness. Reoperation should be considered for patients with local recurrence or resectable distant metastasis of MTC. The findings for both cases supported serum calcitonin as an important marker for the evaluation of disease. Future studies are needed to advance our understanding of its molecular features and improve strategies for its diagnosis and treatment.

A World Health Organization (WHO) report from 2016 states that over 3 million people die annually from air pollution, which places air pollution as the world&rsquo, s largest single environmental health risk factor. Particulate matter (PM) is one of the main components of air pollution, and there is increasing evidence that PM exposure exerts negative effects on the human skin. To see the impact of air pollution on skin aging, we analyzed the effect of PM exposure on human dermal fibroblasts (HDFs) with Western blot, enzyme-linked immunosorbent assay (ELISA), and gene analysis. Cultured HDFs were exposed to PM10 at a concentration of 30 &micro, g/cm2 for 24 h, and their gene/protein expression of inflammatory cytokines, fibroblast chemical mediators, and autophagy were assessed. A total of 1977 genes were found to be differentially expressed following PM exposure. We observed a significantly increased expression of pro-inflammatory genes interleukin (IL)-1&beta, IL-6, IL-8 and IL-33 in dermal fibroblasts exposed to PM10. Protein expression of IL-6 and IL-8 also significantly increased, which complemented our gene analysis results. In addition, there was a significant increase in cytochrome P450 (CYP1A1, CYP1B1), matrix metalloproteinase (MMP-1, MMP-3) mRNA expression, and significant decrease in transforming growth factor (TGF)-&beta, collagen type I alpha chain (COL1A1, COL1A2), and elastin (ELN) mRNA expression in PM-exposed dermal fibroblasts. Protein expression of MMP-1 was significantly increased and that of TGF-&beta, and procollagen profoundly decreased, similar to the gene analysis results. Autophagy, an integrated cellular stress response, was also increased while transmission electron microscopy (TEM) analysis provided evidence of PM internalization in the autolysosomes. Taken together, our results demonstrate that PM10 contributes to skin inflammation and skin aging via impaired collagen synthesis. Increased autophagy in our study suggests a reparative role of autophagy in HDFs stressed with PM, but its biological significance requires further research.

A World Health Organization (WHO) report from 2016 states that over 3 million people die annually from air pollution, which places air pollution as the world’s largest single environmental health risk factor. Particulate matter (PM) is one of the main components of air pollution, and there is increasing evidence that PM exposure exerts negative effects on the human skin. To see the impact of air pollution on skin aging, we analyzed the effect of PM exposure on human dermal fibroblasts (HDFs) with Western blot, enzyme-linked immunosorbent assay (ELISA), and gene analysis. Cultured HDFs were exposed to PM10 at a concentration of 30 µg/cm2 for 24 h, and their gene/protein expression of inflammatory cytokines, fibroblast chemical mediators, and autophagy were assessed. A total of 1977 genes were found to be differentially expressed following PM exposure. We observed a significantly increased expression of pro-inflammatory genes interleukin (IL)-1β, IL-6, IL-8 and IL-33 in dermal fibroblasts exposed to PM10. Protein expression of IL-6 and IL-8 also significantly increased, which complemented our gene analysis results. In addition, there was a significant increase in cytochrome P450 (CYP1A1, CYP1B1), matrix metalloproteinase (MMP-1, MMP-3) mRNA expression, and significant decrease in transforming growth factor (TGF)-β, collagen type I alpha chain (COL1A1, COL1A2), and elastin (ELN) mRNA expression in PM-exposed dermal fibroblasts. Protein expression of MMP-1 was significantly increased and that of TGF-β and procollagen profoundly decreased, similar to the gene analysis results. Autophagy, an integrated cellular stress response, was also increased while transmission electron microscopy (TEM) analysis provided evidence of PM internalization in the autolysosomes. Taken together, our results demonstrate that PM10 contributes to skin inflammation and skin aging via impaired collagen synthesis. Increased autophagy in our study suggests a reparative role of autophagy in HDFs stressed with PM, but its biological significance requires further research.

This case report describes a 53-year-old male patient with persistent hypertension and hypokalaemia. Laboratory tests showed that the patient had hypokalaemia, hypocalcaemia and reduced urine calcium/creatinine. Levels of aldosterone and renin activity were increased significantly. Serum levels of adrenocorticotropic hormone, plasma total cortisol level, 24-h urinary-free cortisol, catecholamines, thyroid stimulating hormone and free tetraiodothyronine were normal. A novel single heterozygous mutation (c.836T> G [E6]) was found after full sequencing of the solute carrier family 12 member 3 ( SLC12A3) gene exons. The patient was diagnosed as having primary hypertension with Gitelman syndrome (GS). These findings triggered the careful consideration of whether a monistic or dualist approach to the diagnosis of this patient was the most appropriate. Monism may not always be the most appropriate approach for the diagnosis of coexistent hypertension and hypokalaemia. Consideration should be given to the possibility of the independent existence of distinct diseases (i.e. dualism) when secondary hypertension cannot be confirmed by conventional examinations and when a genetic diagnosis is crucial. As a common cause of hypokalaemia with a high level of clinical phenotypic variation, GS does not conform to the usual diagnostic criteria. It should also be noted that single heterozygous SLC12A3 gene mutations can cause disease symptoms and other genetic mutations might be involved in the pathogenesis of GS.

Background and aims: Marked hypercholesterolemia, defined as low density lipoprotein cholesterol (LDL-C) levels ≥ 190 mg/dL, may be due to LDLR, APOB, and PCSK9 variants. In a recent analysis, only 1.7% of cases had such variants. Our goal was to identify other potential genetic causes of hypercholesterolemia. Methods: In a total of 51,253 subjects with lipid testing, 3.8% had elevated total cholesterol >300 mg/dL and/or LDL-C≥190 mg/dL. Of these, 246 were further studied, and 69 without kidney, liver, or thyroid disease and who met Dutch Lipid Clinic Network criteria of ≥6 points had DNA sequencing done at the LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1, ABCG5, ABCG8, CYP27A1, LIPA, LIPC, LIPG, LPL, and SCARB1 gene loci and also had 10 SNP analysis for a weighted high LDL-C genetic risk score. Results: In the 69 subjects with genetic analyses, the following variants were observed in 37 subjects (53.6%): LDLR (n = 20, 2 novel), ABCG5/8 (n = 7, 2 novel), APOB (n = 3, 1 novel), CYP27A1 (n = 3, 1 novel), LIPA (n = 2, 1 novel), APOE (n = 2), LIPC (n = 1, novel), LIPG (n = 1, novel), and SCARB1 (n = 1); 14 subjects (20.3%) had a high polygenic score, with 4 (5.8%) having no variants. Conclusions: Our data indicate that in addition to variants in LDLR, APOB, PCSK9, APOE, LDLRAP1, and STAP1, variants in ABCG5/8, CYP27A1, LIPA, LIPC, and LIPG may be associated with hypercholesterolemia and such information should be used to optimize therapy. Fil: Corral, Pablo. Universidad Fasta; Argentina Fil: Geller, Andrew S.. Boston Heart Diagnostics; Estados Unidos Fil: Polisecki, Eliana Y.. Boston Heart Diagnostics; Estados Unidos Fil: Lopez, Graciela Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Bañares, Virginia Gabriela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; Argentina Fil: Cacciagiu, Leonardo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Berg, Gabriela Alicia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Hegele, Robert A.. University Western Ontario; Canadá Fil: Schaefer, Ernst J.. Boston Heart Diagnostics; Estados Unidos Fil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina

ÖZETGen analizleri sağlık alanında biyoteknoloji uygulamalarının önemli bir basamağını oluşturmaktadır. Hukuk alanında gen analizlerinden yararlanılmaktadır. DNA analizleri ile çocuğun ana ve babasının kim olduğu tespit edilerek soybağının kurulmasında kesine yakın sonuçlara ulaşılmaktadır. Ceza davalarında, suçlunun ya da mağdurun vücudundan alınan ve olay yerinde bulunan herhangi bir doku, saç teli, tırnak, sperm ve kan gibi organik örneklerle yapılacak DNA testi sonucunda aydınlatılamamış ya da şüphe duyulan hususlar netliğe kavuşturularak, mağdur veya suçlunun kimliğinin tespiti kolaylaşmaktadır.Tez çalışmamızda hukuki ve etik boyutuyla gen analizleri ele alınmış, gen araştırmalarının hukuksal çerçevesine ve genetik çalışmalara ilişkin karşılaştırmalı hukuktaki düzenlemelere yer verilmiştir. Çalışmamıza aynı zamanda, kişisel veri olarak gen analizleri konusu incelenerek, Kişisel Verilerin Korunması Kanunu kapsamında değerlendirmelere yer verilmiştir.ABSTRACTGene analysis is an important stage in the applications of biotechnology in health care. Gene analysis has a lot of applications in legal issues. By DNA analysis, it is possible to determine the identity of the mother and father of the child and to make decisions for the establishment of the genealogy. In criminal cases, to clarify the unidentified or suspected events, the identification of the victim or the offender can be made easier by DNA testing of any criminal or victim's body and any organic samples such as hair, claws, nails, sperm and blood at the crime scene.In our thesis, the genetic analysis was handled with legal and ethical aspect, and the legal framework of genetic researches and comparative legal regulations related to genetic studies were discussed. We studied the gene analysis as a personal data, and made assessments in the scope of the Personal Data Protection Act.

Prostat kanseri günümüzde erkek toplumunu ilgilendiren ve ölümle sonuçlanan en ciddi kanser türlerindendir. Genellikle 50 yaşından sonra görülmeye başlar ve ileri yaşlarda görülme sıklığı artar. Prostat kanserinin erken evrede teşhisi mortalite ve morbiditeyi azaltılması açısından önem taşımaktadır. Ancak prostat kanseri başlangıç tedavisini takiben kanserin büyümesi yavaş olabilir ve özellikle yüksek riskli prostatkanseri olan erkeklerin % 30-90'ında nüks oluşabilmektedir. Prostat kanseri tanısında en yaygın kullanılan belirteç olan prostat spesifik antijen (PSA)'in özgüllüğü ve pozitif öngörü değeri düşük olup kanser tanısı için mutlak alt sınır değeri henüz tanımlanamamıştır. Radikal prostatektomi sonrasında takipte iki defa ölçülen PSA değerinin >0.2 ng/mL üzerinde ve radyoterapi sonrasında ise nadir PSA seviyesinin ≥2 ng/mL üzerindeki artışı biyokimyasal nüks olarak tanımlanmaktadır. Kallikrein (KLK) gen ailesi hem DNA hem de amino asit seviyesinde önemli homolojileri paylaşan salgılanmış serin proteazları kodlayan 15 gen içerir. İnsan kallikrein gen ailesinin iki üyesi, prostat spesifik antijen ve insan kallikrein 2, prostat kanseri biyobelirteçleri olarak klinik uygulamada kullanılmaktadır. Çalışmamız kapsamında 34 adet tekrarlayan 36 adet tekrarlamayan prostat kanseri ve 19 normal doku örneklerinde 15 adet KLK gen ekspresyon düzeylerinde değişimleri incelenmiştir. Bu noninvaziv yöntemi PKa tanısında güçlü̈ bir aday yapmaktadır. Sonuç olarak, tekrarlayan PKa'da KLK gen ailesinin ekspresyon seviyelerindeki farklılık literatürde ilk kez tarafımızdan gösterilmiştir. PSA'nın rutin muayenede kolay uygulanabilir olması ve prostat kanserinin diğer KLK'lar ile olan ilişkisi incelenmiştir. Sonuçlarımız, PKa'da farklı eksprese olan KLK'ların nüks belirteci olarak kullanılabileceğini göstermiştir.Anahtar Kelimeler : Prostat Kanseri, KLK gen ailesi, gen ekspresyonu Prostate cancer is one of the deadliest cancer types affecting the male population that results with loss of life. Usually begin to appear after the age of 50, and the incidence increases with advanced age. Diagnosis of prostate cancer at the early stage is important in reducing mortality and morbidity. However, after initial treatment, cancer growth may be slow and recur in 30-90% of male patients with increasedprostate cancer risk. The specificity and positive predictive value of prostate specific antigen (PSA), the most widely used biomarker for prostate cancer, is low and the absolute lower limit value for cancer diagnosis has not yet been identified. Biochemical recurrence is defined as an increase in PSA value >0.2 ng/mL, measured twice after radical prostatectomy and nadir PSA value ≥2 ng/mL, after radiotherapy.The Kallikrein (KLK) gene family consist of 15 genes encoding secreted serine proteases that have relevant homologies at both the DNA and amino acid level. Two members of the human kallikrein gene family, prostate specific antigen (PSA) and human kallikrein 2 (hK2), are used clinically as prostate cancer biomarkers. In our study, changes in 15 KLK gene expression levels in 34 recurring 36 non-recurring prostate cancers and 19 normal tissue specimens were investigated. This noninvasive method makes a strong candidate for PCa diagnosis. In conclusion, the difference in expression levels of the KLK gene family in recurrent PCa has been shown for the first time by us in the literature. Easy application of PSA in routine examination and the relationship between prostate cancer and other KLKs have been examined. Our results have shown that KLKs, which are differently expressed in PCa, can be used as recurrence markers.Key words: Prostate Cancer, KLK gene family, gene expression 72

Helicobacter cinaedi感染症は免疫不全患者に起こりやすく，近年，本菌による感染症の報告が散見されるが，血液培養結果に占める本菌の分離頻度は低い．われわれは，1年10ヶ月間に3例のHelicobacter cinaedi:菌血症患者を経験した．症例1は77歳女性，間質性肺炎でステロイド・免疫抑制剤使用中，症例2・3はともに71歳男性，肺癌で抗癌剤加療中であった．3症例とも培養では菌の同定に至らなかったが，症例1は16S rRNA遺伝子の塩基配列をもとにした解析，症例2・3はnested polymerase chain reaction法で同定した．Helicobacter cinaedi菌血症は再発率が高く，また，抗菌薬の長期投与が必要であるが，本菌の同定には遺伝子解析による評価が有用であると考えられた． Helicobacter cinaedi is typically isolated from immunocompromised patients. Some reports of infection caused by H.cinaedi have been found in recent years. We experienced three cases of H.cinaedi bacteremia in one year and ten months in our hospital, although the detection of H.cinaedi in blood cultures is extremely rare. In case 1, a 77-year-old female had been treated with a steroid and immunosuppressive agent for interstitial pneumonia. In cases 2 and 3, two 71-year-old men had been treated with chemotherapy for lung cancer. Although the identification of the bacteria could not be performed by the culture method in the three cases, H.cinaedi bacteremia was diagnosed by a 16S rRNA gene sequencing analysis in case 1, and by nested PCR in cases 2 and 3. H.cinaedi bacteremia often tends to recur and also requires prolonged antimicrobial therapy. We believe that gene analysis is useful in the identification of H.cinaedi.

Objective: The aim of this paper was to report the first case of Kennedy disease misdiagnosed as polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Clinical Presentation and Intervention: A 58-year-old Chinese man presented with limb numbness, progressive limb proximal weakness, lymph node and thyroid enlargement, edema, pigmentation in the lower limb, and obvious gynecomastia, which was initially diagnosed as POEMS syndrome and was treated with dexamethasone and small doses of cyclophosphamide without any improvement after 6 months. Finally, the patient diagnosis was confirmed as Kennedy disease (KD) by gene analysis. Conclusion: This case suggests that clinicians should pay more attention to the differential diagnosis between KD and POEMS syndrome. Gene analysis was helpful in detecting this rare confusing disease in this patient.

Dissertação de Mestrado, Engenharia Zootécnica, 10 de abril de 2017, Universidade dos Açores. Factores como radiação, poluentes tóxicos ambientais, stress oxidativo e choque térmico (CT) são muitas vezes apontados como responsáveis pela apoptose em embriões de bovinos, podendo este ser um dos fatores da baixa fertilidade observada nos bovinos durante a época de verão. Desta forma o presente estudo foi elaborado no sentido de avaliar a capacidade de maturação in vitro de ovócitos, após terem sido submetidos a um CT durante 0 (controlo) 6, 12 18 e 24 horas de CT1=39,5 °C e CT2=40,5 °C, bem como a expressão genética dos genes responsáveis pela sua maturação: Cx43, CDH1, DNMT1, HSPA14 e dos genes de referência, GAPDH e SDHA. Para isso, os complexos cumulus-ovócitos (CCOs) (n= 1124) foram aspirados durante os meses de Inverno e submetidos, respetivamente ao CT1 e CT2. Passadas as 24h, os CCOs foram divididos em dois grupos no qual no primeiro foram registadas as taxas de maturação nuclear (TMN), após a fixação e coloração com aceto-orceina (3:1) e no segundo grupo foi analisada a expressão genética, tendo como genes alvo Cx43, CDH1, DNMT1, HSPA14 e como referência os genes de manutenção GAPDH e SDHA. A duração do stress térmico resultou numa diminuição significativa (p

In this study, the effects of temperature-shift (from 30 to 25 °C) and temperature-constant (at 30 °C) cultivation on the mass of Monascus fuliginosus CG-6 mycelia and concentration of the produced monacolin K (MK) were monitored. The expression levels of the MK biosynthetic genes of M. fuliginosus CG-6 at constant and variable culture temperatures were analysed by real-time quantitative polymerase chain reaction (RT-qPCR). The total protein was collected and determined by liquid chromatography-electrospray ionisation with tandem mass spectrometry (LC-ESI-MS/MS). Results showed that the maximum mycelial mass in temperature-shift cultivation was only 0.477 g of dry cell mass per dish, which was lower than that in temperature-constant cultivation (0.581 g of dry cell mass per dish); however, the maximum concentration of MK in temperature-shift cultivation (34.5 μg/mL) was 16 times higher than that in temperature-constant cultivation at 30 °C (2.11 μg/mL). Gene expression analysis showed that the expression of the MK biosynthetic gene cluster at culture temperature of 25 °C was higher than that at 30 °C, which was similar to the trend of the MK concentration, except for individual MK B and MK C genes. Analysis of differential protein expression revealed that 2016 proteins were detected by LC-ESI-MS/MS. The expression level of efflux pump protein coded by the MK I gene exhibited the same upregulated trend as the expression of MK I in temperature-shift cultivation. Temperature-shift cultivation enhanced the expression of proteins in the secondary metabolite production pathway, but suppressed the expression of proteins involved in the mycelial growth., U radu je istražen utjecaj promjene temperature (s 30 na 25 °C) i konstantne temperature uzgoja (30 °C) na masu micelija plijesni Monascus fuliginosus CG-6 i koncentraciju proizvedenog monakolina K, pri čemu je razina ekspresije gena za biosintezu monakolina praćena metodom RT-qPCR. Ukupni su proteini određeni metodom LC -ESI-MS/MS. Rezultati pokazuju da je maksimalna masa micelija dobivenog pri promjeni temperature uzgoja bila samo 0,477 g suhe tvari po Petrijevoj zdjelici, što je znatno manje od one dobivene uzgojem pri konstantnoj temperaturi (0,581 g suhe tvari po Petrijevoj zdjelici). Međutim, maksimalna koncentracija monakolina K pri promjeni temperature uzgoja bila je 34,5 μg/mL, tj. 16 puta veća od one dobivene uzgojem pri konstantnoj temperaturi (2,11 μg/mL). U skladu s tim, utvrđeno je da je razina ekspresije klastera gena za biosintezu monakolina K veća pri 25 nego pri 30 °C, osim za gene MK B i MK C. Analizom diferencijalne ekspresije proteina otkriveno je 2016 različitih proteina, identificiranih metodom LC-ESI-MS/MS. Ekspresija proteinske pumpe koju kodira MK I gen pokazala je isti trend kao i ekspresija samog gena pri promjeni temperature uzgoja s 30 na 25 °C. Promjena temperature uzgoja povećala je ekspresiju proteina uključenih u sintezu sekundarnih metabolita, no smanjila ekspresiju proteina odgovornih za rast micelija.

Mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. The M. leprae bacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p > 0.05) in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. leprae stimulus. Keywords: ERBB2, Gene analysis, Leprosy

Gastrointestinal stromal tumors (GISTs) developing in the colon are rare, accounting for

Cyanobacteria are microorganisms that pose a serious threat to the aquatic waterways through the production of dense blooms under eutrophic conditions and the release of toxic secondary metabolites—cyanotoxins. Within cyanobacteria, the colonial planktonic Microcystis aeruginosa is widely distributed in both fresh and brackish aquatic environments throughout the world being frequently observed in the Portuguese water systems. Apart from the well-established distribution of M. aeruginosa in Portugal, knowledge of its genetic diversity and population structure is unknown. Therefore, in this study twenty-seven strains were obtained from the North, Centre and South regions of Portugal and were subjected to extensive phylogenetic analyses using simultaneously four distinct genetic markers (16S rRNA, 16S-23S ITS, DNA gyrase subunit ß and cell division protein (ftsZ)) encompassing in total 2834 bp. With this work we characterized the phylogenetic relationship among the Portuguese strains, with the southern strains showing higher genetic structure relatively to the North and Centre strains. A total of fifteen genotypes were determined for M. aeruginosa in Portuguese water systems revealing a high genetic diversity. This is also the first study to report geographic variation on the population structure of the Portuguese M. aeruginosa. © 2016, Springer Science+Business Media Dordrecht. The authors acknowledge the Portuguese Fundação para a Ciência e a Tecnologia (FCT) for the PhD fellowship to Cristiana Moreira (Ref. SFRH/BD/47164/2008). Agostinho Antunes was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT and European Regional Development Fund (ERDF) in the framework of the program PT2020 and the FCT project PTDC/AAG-GLO/6887/2014.