DEPARTAMEMT OF MEDICAL GENETICS (1971 – 2008 г.) D.Toncheva, S.Lalchev Localization and structure of the Department The Department of Medical Genetics is founded on 1.06.1971 and belongs to the Institute for specialization and improvement of doctors (ISUL) following the order of the Rector of the Institute Prof. Dr. Lubomir Shindarov. It belongs to ISUL together with the other small research and diagnostic units from different institutions related to medical genetics: Scientific Laboratory of Medical Genetics in Medical Faculty of Sofia, the scientific group at the Department of Endocrinology of ISUL, Department of preventive genetics at the Scientific Institute of Hygiene in MNZ (founded in 1969, led by Prof. Maria Tsoneva), newly appointed staff to Department of teratology to the Department of Pathological Anatomy of ISUL (led by Professor Blaga Konstantinova). In the initial period the collaborators of the Department worked in three small rooms of the polyclinic of ISUL. After the formation of the Medical College (MA) in 1972 the Department was included in the structure of the Scientific medico- biological Institute (NMBI). The department was expanded by two large laboratory facilities and a small office in a newly founded Institute of Hygiene (in 1974) and later was transferred entirely in 11 rooms on the second floor of ISUL. The structure of the department was formed in the following manner: Cytogenetic laboratory with tissue culture boxes and photolaboratory, Laboratory of Molecular Genetics, Immunogenetic laboratory, Office of the Head of Department, Office of Associate Professors in the Department, three surgeries for other academic staff and Cabinet for medical and genetic counseling. This hard-built structure creates conditions for the development of the three basic kinds of activities - teaching, research and diagnostic advisory. In 2000 the Department was transferred to the Dean of the Medical Faculty of Sofia and was moved to SBALAG "Maichin Dom" of the 13th floor. We updated the cabinets and created a comfortable environment to work. To the existing laboratories of the Department we established additional new laboratories for prenatal diagnosis and molecular cytogenetics and introduced modern techniques of analysis and diagnosis. Facilities of the Department have been enriched with new equipment for molecular genetic studies, molecular cytogenetic analysis and microchip technology through grants from the University of Wales in international projects and infrastructure projects to the Ministry of Education, the Monetary Union of the University of Sofia. The department is equiped for molecular genetic studies, apparatus DHPLC (donated by the American company Transgenomics) for single nucleotide polymorphism analysis (SNPs), a software system for image processing of chromosomes (Metasystem), programs for molecular cytogenetic analysis - Fluorescent in situ hybridization (FISH), multicolor FISH, comparative genomic hybridization (CGH), a unique apparatus for microarray analysis (GenePix), real time PCR and the only one of its kind apparatus in the country MALDI-TOF-TOF proteomic analysis purchased after national and international projects; equipped computer room and connected computers in the network. In connection with the infrastructure project of the Ministry of Education in 2006 the Rector of Sofia University issued an order for the creation of a National Genome Center for Common Diseases with laboratories for genome and expression analyses. Department’s Staff Following the order of the minister of Health Dr.Cyril Ignatov (1971), Prof.Dr.Maria Todorova Tsoneva was appointed as Head of the Department of Medical Genetics (at that time office manager of the Department of Biology at Military Academy-Varna and Head of the Research Laboratory of Medical Genetics at the Military Academy-Sofia. The first employers of the Department of Medical Genetics were: Dr. Maria Tsoneva, doctor of medical sciences, Head of the Department, Dr. Maria Krachunova (Scientific fellow of the Military Academy–Sofia), Andronika Radanova (biologist from the Military Academy– Sofia), Tzvetana Bivolarska (laboratory technician, Military Academy–Sofia), Dr.Ksenia Skachokova (Assistant Professor at the Department of Pediatrics, ISUL), Tanka Lozanova (biologist from the Department of Pediatrics, ISUL), Maria Stoykova (biologist from the Department of Pediatrics, ISUL), Liliana Yordanova (research associate from the Department of Endocrinology, ISUL), Maria Guslekova (laboratory technician from the Department of Endocrinology at ISUL), Dr. Veneta Georgieva (Scientific fellow of the NIH in Ministry of National Health), Dr. Maria Mavrudieva (Scientific fellow of NIY in Ministry of National Health), Dr. Nadejda Proynova (Scientific fellow of the NIH in Ministry of National Health), Dr. Petranka Ilieva (Assistant Professor of the Department of teratology in ISUL), Dr. Stoyan Lalchev (Assistant professor of the Department of teratology in ISUL), Dr. Maria Tsancheva (Assistant professor from the section on teratology in ISUL), Dr Mitko Abadjiev, chief assistant professor (transferred from the Department of Neurology at ISUL in 1972 as its main interests were in a degenerative neurological diseases and hereditary diseases in neurology), Dr Aneta Totseva (Scientific fellow, who has worked abroad on the problems of radiation genetics), Dimitar Tanev (biochemist transferred from the Department of Clinical Laboratory ISUL). Later on, in the structure of the Department of medical genetics were employed Dr. Lukan Lukanov (assistant professor), Dr. Draga Toncheva (assistant professor), Dr. Maria Nacheva (assistant professor), Dr.Vurban Ganev (assistant professor), Dr.Stephan Slavchev (assistant professor), Dr.Robert Yulzari (assistant professor), Dr.Radoslava Bujarova (assistant professor), Dr.Ognian Uzunov (assistant professor). Under the direction of Prof. Maria Tsoneva were established medical and genetic centers in the best medical institutes in the country and National genetic network was created. In the period from 1990 to 2000 the composition of the department gradually began to change because a part of the collaborators retired, another part left their jobs. The staff was reduced by 40%. During the period 2000-2004 some academic staff retired (Dr. P. Ilieva, Dr. M. Nacheva, Dr. and Prof. M. Tsancheva) and two assistants (Dr. Slavchev and Dr. Jordanov ) and biologists (Sr. Atanasova, N. Kalchishkova and E. Grozeva) went to work abroad. Dr. Dimitar Azmanov (Assistant professor transferred from the Military Academy Stara Zagora), left because of going to work abroad). Albena Zaharieva (biologist, assistant) changed her working place in a pharmaceutical company. The main staff of the department was replaced by a new staff who successfully passed a competitive exam or prepared their master works in the Department. The academic staff of the Department now includes Prof.Stoyan Lalchev, Prof.Draga Toncheva, Dr.Ivanka Dimova (chief assistant professor) Dr.Savina Hadjidekova (senior assistant professor), Boriana Zaharieva (senior assistant professor), Dr.Elica Becheva (assistant professor), Sena Karachanak (assistant professor), Dragomira Nikolova (assistant professor). The biologists at the department are Adelina Yosifova, Blaga Rukova and Desislava Nesheva. The habilitated collaborators in the Department of Medical Genetics are the following: Dr. Mitko Abadjiev (Associate Professor, 1974), Dr. Veneta Georgieva (Associate Professor, 1982), Dr. Stoyan Lalchev (Associate Professor, 1989), Dr. Draga Toncheva (Associate Professor, 1999, Professor, 2008). Assoc.Prof. Stoyan Lalchev took the leadership of the Department (from 1989 to 2000). From 2000 until present the Head of the Department of medical genetics is Prof. Draga Toncheva. Educational and teaching activity Postgraduate education At the beginning the educational activity was directed to establish basic courses in medical genetics for doctors to obtain the specialty of Medical Genetics, medical genetic courses adapted to professionals of other disciplines - neurology, pediatrics, obstetrics and gynecology, internal medicine, psychiatry, epidemiology, dentistry and others; as well as integrated education in separate lectures on medical genetic specialized courses in other departments in ISUL and Medical College. The department organized annual coursed (2-3 per year), lasting for one week, on the basis of former district hospitals for the implementation of the new achievements of medical genetics in health care practice. They were accepted with a great interest from the doctors and contributed to the increase of the number of patients to medical counseling cabinet. Such courses were held in almost all district hospitals: Varna (1972), Bulgaria (1972), Pleven, Plovdiv and Veliko Turnovo (1972), Ruse, Stara Zagora and Dobrich (1973), Razgrad and Gabrovo (1974), Shumen and Smolyan (1975), Sliven (1976), Vidin and Haskovo (1977), Yambol and Targovishte (1978); Tolbuhin and Sofia (1979), Blagoevgrad (1984), Kyustendil (1985), Mihaylovgrad (1986), Pernik and Bourgas (1987 ), Kardzhali (1988), Feliko Tarnovo and Bourgas (1990), District Hospital in Sofia (1992). Thematic courses were organized, such as: "Medico-genetic advisory assistance - organization and tasks" (1989), Psychiatric Genetics "(1987)," What's New in Dentistry "(1987)," Genetic problems of human reproduction "(1990) and others. In 1976 the Ministry of Health established a specialty «Medical Genetics» and the department developed the first curriculum for specialization. We are proud that we have prepared the first specialists in medical genetics before other European countries that are just about to introduce this subject. The specialization program underwent several updates in 1985, 1991, 1996, 2000, 2002. The department was and remains the major base for specialization. An individual training passed more than 50 doctors, while basic courses for acquiring specialty - over 40 physicians. Such long courses (from 1-2 months) were conducted in 1977, 1984, 1994, 1999, 2007. The main part of the preparation of specialized doctors is held by individual training. State exams for the acquisition of clinical specialty of medical genetics are held before a committee of habilitated teachers of the Department. By SDO educational program, the Department prepares doctors belonging to the network of other clinical specialties with basic knowledge of genetics for the genetic advisory units at the medical faculties in the country and in some district hospitals. After 2000 the organization of the cabinets for genetic counseling was maintained only at the university hospitals while the rest of the cabinets ended their function. For the preparation of the doctors were issued the following textbooks and practical guidances: 1. „Heredity and diseases”, under the edition of M.Tzoneva and dr.P.Genkova, Med.and Phys., Sofia, 1973 2. „ Clinical and genetic methods in medical practice”, under the edition of М. Abadjiev, CNMI, Sofia, 1973 3. „Chromosomal syndromes – cytogenetic and clinical picture”, under the edition of М. Tzancheva, CNMI, Sofia, 1982 4. „Heredity and health”, under the edition of M.Tzoneva, Med. and Phys., Sofia, 1980 5. „Heredity and diseases”, under the edition of M.Tzoneva, P.Genkova, 2nd edited edition, Med. and Phys., Sofia, 1976 6. „Chromosomal diagnostics”, under the edition of M.Tzoneva, Med. and Phys., Sofia, 1978 7. „Hereditary diseases in children”, under the edition of Br.Bratanov and M. Tzoneva, Med. and Phys., Sofia,, 1976 8. „Hereditary pathology”, from М. Tzoneva, in: „Clinical pediatrics”, p. I, under the edition of Br.Bratanov, 2nd edited edition, Med. and Phys., Sofia, 1978 9. „Genetic problems and the internal medicine” by М. Tzoneva. in: „Guidance of internal diseases”p. I, under the edition of A.Maleev and Sv.Ivanov, Med. and Phys., 1983 10. «Hereditary pathology» by М. Tzoneva. in: «Clinical pediatrics», p. I, under the edition of Br.Bratanov, Med. and Phys., 1983 11. «Medical and genetic counseling/prophylactics of hereditary diseases» under the edition of M.Tzoneva, Med. and Phys., Sofia, 1984 12. «Health and social problems of the hereditary diseases» by М. Tzoneva. in: «Population, health and health prevention» under the edition of Hr. Petkov, Med. and Phys., Sofia, 1986 13. «Cystic fibrosis» by М. Tzoneva, М. Zlateva, Zl. Kolev, Med. and Phys., Sofia, 1983 14. «Manual of hereditary diseases». under the edition of М. Tzoneva, Med. and Phys., Sofia, 1988 15. «Clinical genetics of the internal diseases», under the edition of Ist. Kurnolski, Med. and Phys., Sofia, 1989 16. «Inherited connective tissue failures» by Т. Milkovska-Dimitrova, А. Karakashov, V. Georgieva, Med. and Phys., Sofia, 1995 17. «Medical genetics for surgeons» by D. Toncheva. in "Surgery. Foundations of surgery. Volume I." (under the edition of prof. Damian Damianov), Znanie, Sofia, 417-425, 2004 18. «Hereditary forms of prion diseases» by D. Toncheva. in «Prion diseases». Under the edition of I.Velcheva, D. Stoyanov, АРСО, 28-38, 2005 19. Surgery on the era of genomics and cell therapy. D.Toncheva. in "Foundations of surgery. Volume II." (under the edition of prof. Damian Damianov), Znanie, Sofia In 1999 for the first time a two weeks’ course was organized for nurses on „Prophylactics of hereditary diseases and defects – place and tasks of the място и задачи of the medical college staff”. Students’ education Students from the Medical Faculty At the beginning medical students have studied as an optional subject “Foundations of medical genetics». In 1975 a regular training of the students belonging to the Medical Faculty Sofia was introduced. The educational program was held in the IV semester with altogether 28 hours – 14 hours lectures and 14 hours exercises. In 1992 a facultative course “Chromosomal pathology” was organized for students, who revealed interest to enlarge their knowledge. After the renewal of the training course of the Medical Faculty in 1992, the subject of medical genetics was transferred in the third course in the University, V semester, with increased number of taken hours - 60 educational hours (30 hours lectures and 30 hours exercises) and passing an exam. In 2005 the Department of Medical Genetics introduced an optional course for medical students entitled "Genetic bases of the major social diseases” – the duration of the course is 60 lecture hours (credit 1.6).Bulgarian and foreign students have exclusive interest in it. The course ends with an assessment of abstracts. During the seminars students present their research works and the best preparations are delivered as reports during all the six minisympoziums: Minisymposium I. “Genetic bases of the cardiac and respiratory” Minisymposium II. “Immunogenetics” Minisymposium III. “Genetic factors in the pathogenesis of gastrointestinal disorders” Minisymposium IV. “Genetic predisposition to endocrine diseases” Minisymposium V. “Genetics of neuro-psychiatric diseases” Minisymposium VI. “Malignant diseases: genetic markers of diagnostic, prognostic and therapeutic value” The best students receive a special diploma for their presentations and 20 points from the Association of Medical Students in Bulgaria needed for their participation in international exchange programs, and all the rest receive 10 points and diplomas. This activity of the Department gained a high degree in the reports of the Educational office of the Dean in front of the Faculty Committee. After 2000, the educational programs of medical students were renewed. We introduced a test system for the evaluation of knowledge of medical students in medical genetics. The following textbooks of medical genetics were issued: 1. «Bases of molecular genetics» by M.Tzoneva, Е. Boshnakova, 1971 г., issued by the Military Institute-Varna, which was used in medical genetics’ education in the IX semester in 1969 г. 2. «Bases of medical genetics» by М. Tzoneva, Е. Boshnakova,, L. Vasileva, Sofia, 1977 3. «Bases of medical genetics» by М. Tzoneva, М. Abadjiev, 1979 4. “Principles of Medical Genetics”, M. Tzoneva, M. Abadjiev, 1983 (second edition) 5. “Principles of Medical Genetics”, M. Tzoneva, V. Georgieva, D. Valkova L. Vassileva, 1989 6. “Medical Genetics”; Editor D. Toncheva, St. Lalchev; Siela, Sofia, 1999 7. “Medical Genetics in clinical practice”; Editor D. Toncheva; Siela, Sofia, 1999 8. “Medical Genetics: Tests for students”; Editor D. Toncheva, Knowledge, 2004 Since 2004 in the Department of Medical Genetics, during the course of summer study internship programs over 20 foreign students were trained, as a part of the international exchange of medical students (Research Exchange Project Details 2001-2005, organized by International Federation of Medical Students' Association - IFMSA). Students from Czech Republic, Spain, Germany, Greece, Romania, Latvia, and Japan have been working in the department on the topics "Molecular pathways in sporadic and familial cancer" and "Molecular cytogenetic studies of ovarian tumors". Students from the Pharmaceutical Faculty In 1983 the Council of the Pharmaceutical Faculty approved training programme in “Basics of biology and clinical medicine”, 1/3 of which were provided for medical genetics classes. Profiled textbook edited by Prof. I. Popiliev with co-authors Prof. M. Tzoneva, Prof. P. Shotekov, Associate A. Dourmishev (Medicine and sports, 1992) was prepared for the students. Since 1992 Medical Genetics is approved for an independent discipline in the education programme of the pharmaceutical students, with horarium of 30 hours (15 hours lectures and 15 hours practical cources) and session final exam. Initially, Medical Genetics was studied during the 6th semester (3rd year), but since 1997 it was included in the programme of 8th semester (4th year). Such modification was made in order to help students to understand better the genetic bases of drug dependent teratogenesis, pharmacogenetics, pharmacogenomics, and genetic susceptibility to drugs adverse reactions, subsequently to acquiring knowledge on toxicology, pharmacology and clinical medicine. Students from “St. Climent Ochridski” Sofia University In 1985, the Department of Medical Genetics has proposed a course in Medical (human) genetics for bachelor and master students of the Biological Faculty, as profiled training at the Department of Genetics. The lecturers were subsequently Prof. M. Tzoneva and Assoc. Prof. D. Toncheva. Forty-five diploma and master theses have been created and successfully defended from students of the Biological Faculty, the University of Sofia, under the supervision of Assoc. Prof. D. Toncheva, Assoc. Prof. St. Lalchev and Assoc. Prof. V. Georgieva. Since 1985, at the proposal of the Department of Special Pedagogic and Defectology at Sofia University, lecture course (30 hours) and final exam for students of profile Defectology were introduced in the programme of full-time studying and distance learning students, and held by Assoc. Prof. St. Lalchev. Few years later lecture course was initiated at the Southwestern University in Blagoevgrad with speaker Assoc. Prof. V. Georgieva. The Department of Medical Genetics has great contribution to the establishment of a network for teaching in Medical Genetics in all novel Medical Faculties in Bulgaria, untill they have elected their academicians on the specialty. Prof. M. Tzoneva was lecturer at the Medical Faculty of Varna in 1971-1972; Assoc. Prof. M. Abadjiev and Assoc. Prof. V. Georgieva were lecturers in Medical Faculty of Pleven since the establishment of the faculty up to 1989; Assoc. Prof. Lalchev is lecturer at the Medical Faculty of St. Zagora since 1989. Prof. Toncheva was a guest lecturer at: The European Renal Association, XLII ERA-EDTA Congress, Istanbul, Turkey (2005), University of Wells, College of Medicine, Deptartment of Neuropsychiatric Genetics, 11th EUROTOX Training and Discussion Session "Diet and Cancer", Dusseldorf, (May 16th 2003), International Surgadai symposium as an invited speaker, (Nov. 28-29, 2006) in Tokyo, Japan, Drexel University, Research Center of Biotechnology, Pennsylvania, USA, National Institute of Health & Human Services, Session on "Emerging and Re-Emerging Diseases and Development of Therapeutics". Prof. Toncheva was scientific adviser of over 40 students from the Sofia University in the preparation of their Diploma and Master's theses. Students from Medical Colleges In 1994 was approved a proposal of the Department of Medical Genetics for initiation of human genetics course for nurses, nurse-midwives and laboratory technical staff in the Medical institutes for Bachelor’s degree, later transformed into Medical colleges: in 1995 in Sofia, and in 1997 in Vratza and Blagoevgrad. Prof. Toncheva was a guest lecturer at: NIAID Research Conference in Opatija (Croatia), June 29, 2006, 11.15-11.45, the lecture will be published in the proceedings of the 2006 NIAID Research Conference in Opatija (Croatia); University of Wales College of Medicine , 30th June - 4th July, 2003, at the invitation of Professor Michael Owen, Professor and Head of Department of Psychological Medicine; Drexel University 10.05.2004, 13.00-13.45, at the invitation of Professor Timothy Block; 5th Surugadai Symposium "Genomics and Epigenomics of Human Diseases and Mammalian Development, Tokyo Medical and Dental University ", 29 November 2006, 10.00-10.30, NIAID Research Conference in Opatija (Croatia), June 29, 2006, 11.15-11.45, OMICS in the 21st Century, Fifth International Symposium on Genetics, Health and Disease, Amritsar, India, Feb. 17-19, 2008. Diagnostic, consultative and methodic issues Since its establishment the Department of Medical Genetics provides diagnostic and consultative services, under the jurisdiction of the Minister of Health, as determined by regulation №1126/05.03.1975. Under its guidelines was organized and supported a network of institutions for genetic counselling and laboratories at the Medical Universities of Varna, Plovdiv, Pleven and St. Zagora. In 1986 the Ministry of Health approved National Strategic Programme for Prevention of Genetic Disorders. Thus the Genetic Counseling Institutions were authorized for Genetic Consultative Centres. We are co-authors and participants in the subsequent National programs for diagnosis and prevention of hereditary disorders, genetic susceptibility and congenital anomalies for 2000-2006 and 2008-2013, proposed by the Ministry of Health. Genetic councelors’ service of the department is available for patients with various medical conditions from all over the country: chromosomal disorders, malformations, single gene disorders, multifactorial disorders, pharmacogenetic defects, reproductive failiure, mental retardation, pregnancies at risk and affected by teratogenic impact, malignancies, and others. Annually, over 1000 patients are looking for information from the Genetic counselors of the Department of Medical Genetics and are indicated for genetic testings. For example, in 2003 were tested 963 patients: prenatal and postnatal cytogenetic analysis, molecular-cytogenetic analysis, and 3588 patients applied for genetic counseling. In 2002 the laboratories of Cytogenetics, Molecular genetics, Molecular cytogenetics, and Prenatal diagnostics at the Department of Medical Genetics obtained accreditation status for five years term. After the introduction of the chromosome analysis techniques our CYTOGENETIC LABORATORY has established all methods for chromosome banding (such as GTG, C, NOR), prometaphase analysis, X and Y sex hromatin analysis, sister chromatid exchanges analysis. Annually over 800 patients are being examined. Routine cytogenetic analysis by specialized software programs (MetaSystems, Germany) on the following biological samples is available at the laboratory: peripheral blood cells, bone marrow and solid tumors, for evaluation of chromosome polymorphisms, the influence of environmental mutagens causing chromosomal aberrations and sister chromatid exchanges. Diagnosis is performed for: chromosome disorders in patients with malformations, mental retardation, families with infertility and sterility, indicated for in vitro fertilization; certain chromosomal aberrations in oncohematology and oncology; disclosure of carrier’s status for variety of chromosomal rearrangements, minimal residual disease. The LABORATORY FOR PRENATAL DIAGNOSIS was established in year 2000. Over 300 pregnancies annually are being examined for chromosomal disorders. Indications for routine cytogenetic and FISH chromosomal analysis of amniotyc cells, chorionic villa and fetal peripheral blood cells are as follows: pregnant women aged 35 years or older; with increased risk for fetal malformations and other chromosomal anomalies (such as Down syndrome); abnormal foetal ultrasound and/or biochemical screening (positive maternal serum screening result indicating an increased risk of a chromosomally abnormal fetus); previous livebirth with a chromosome abnormality; previous stillbirth with a potentially viable chromosome abnormality; parental chromosome rearrangement, chromosome mosaicism or sex chromosome aneuploidy, and others. The MOLECULAR CYTOGENETICS LABORATORY is the first established of its kind in Bulgaria and the Balkan region, where many contemporary diagnostic techniques were introduced: Fluorescent in situ hybridization (FISH), Comparative genomic hybridization (CGH), Multicolor FISH (mFISH), Tissue microarray for molecular-cytogenetic studies with ISI software (MetaSystems, Germany). Certain chromosomal abnormalities are being assessed in oncohematological disorders, different solid tumors, also for prenatal diagnosis application and for spontaneous abortions diagnostic conclusion. The laboratory is reference in Bulgaria and neighbouring countries in diagnosis of complex chromosome rearrangements, translocations and chromosome markers. At the LABORATORY OF MOLECULAR GENETICS are available the following techniques: Polymerase chain reaction (PCR), single nucleotide polymorphism (SNPs) genotyping by Allele specific fluorescent labeled primers extension, Mutation detection by DHPLC, DNA microarray analysis of copy number variations in oncogenes and tumorsuppressor genes, Real-time PCR expression analysis, ect. We perform DNA genotyping analysis of human papilloma virus (HPV), mutations in p53, in RAS oncogenes, loss of heterozygosity, cytochrome P450 monooxygenase polymorphisms, polymorphisms in multidrugs resistance genes (MDR) and xenobiotic metabolizing enzymes. Samples from patients with lesions of the uterine cervix, solid tumors, and some common disorders might also be analyzed. Initial for Bulgaria was the research project on microstructural aberrations in children with mental retardation and congenital malformations by DNA-microarray technology. GENETIC COUNSELING ROOM at the department is at the disposal of patients from all over the country, affected by various pathology - chromosomal aberrations, malformations, single gene and multifactorial disorders, impact of teratogens, pharmacogenetic defects, reproductive failure, mental retardation, pregnancies at risk, malignancies, ect. Genetic counselors - medical doctors with specialty in Medical Genetics, evaluate specific phenotype features, perform pedigree analysis, estimate genetic risk, diagnose and perform specific genetic tests, advice and inform on prevention, susceptibility and treatment of hereditary diseases. Patients with a family history of genetic disorders, sterility and infertility, previous livebirth with malformation and/or mental retardation and failure to thrive, previous still-birth and/or spontaneous abortions, and, women with pregnancies at risk, after mutagen impact and other are indicated for our admission. Supported by the National Genetics Counselor of the Ministry of Health, the organizational and methodical activities of the Department were focused on the establishment and development of the genetic centers in the Medical Faculties in Varna, Plovdiv, Stara Zagora and Pleven, and the genetic consultation rooms at the regional hospitals. Initially, Prof. M. Tzoneva was appointed as a National consultant in medical genetics and was employed on this position until 1989. Since 1989 Assoc. Prof. Stoyan Lalchev was designated and re- elected in 2007 as National consultant in medical genetics by the Minister of Health. Scientific and Research activities The initial research interests of the Department of Medical Genetics were in the field of: 1. Evaluation of the type and the frequency of hereditary disorders in Bulgarian population; 2. Identification of mutation inducing factors in our biological and social environment; This research that involved many ecological issues, had major influence on the preparation of the National Programme for Prevention of Genetic Disorders of the Ministry of Health. Principal executive of this programme was the Head of the Department and National Genetics Counselor Prof. M. Tzaneva. Participants in the execution of the programme were researchers from the Ministry of Health and the Bulgarian Academy of Sciences. Some of the major initial research theses of the Department were as follows: 1. Analysis of the type and the frequency of chromosome disorders in Bulgaria. To organize and perform such project was very difficult and time consuming task. During its execution researchers from the department were trained in cytogenetic testing and diagnostics. Prof. M. Tzoneva has introduced the chemical Fazeolosaxine, for stimulation of the cell cycle and division in short termed leukocyte cell cultures, applied in the clinical cytogenetic analysis. Dr. Maria Krachunova estimated the effect of the immune system variants for the susceptibility to schizophrenia. Dr. V. Georgieva performed the study “Genetic monitoring of workers in petrol and oil manufacturing companies”. Dr. M Tzancheva assessed the effect of the neuroleptics as mutagens. Researchers from Vietnam, , analyzed the mutagenic effect of Streptolysine O (Chan Thi Lien) and of the pesticide Kilakar (Dang Chi Than). Joint research project between Bulgaria and Greece was performed between 1983 and 1988, entitled “Mutegenesis in environment. Identification and evaluation of mutagen activity of some pesticides”. Our partner was Prof. Andreas Kapas from the Institute of Biology at The National Research Centre “DEMOCRATIS” in Atina. The effects of two chemicals (Endodan and Kilakar) applied in the agricultural industry in Bulgaria and Greece was evaluated during the first 2 years and it was concluded that both of them have weak mutagenic effect in human leukocyte cultures. From 1985 up to 1988 two other chemicals were also examined. The researchers revealed high rate of chromosome aberrations and sister chromatid exchanges, when cells are treated with Benomil, as for Chloracetophone, the mutagen effect assessed was strongly diminished, which made it applicable in industry. 2. Analysis of the polymorphisms in Glucose-6-phosphate dehydrogenase deficiency and different haemoglobinopathies in Bulgarian population. This project was granted by WHO in 1976 under the regulation of two subsequent contracts for funding. The WHO was very interested in such association study in the Bulgarian population since our data had significant impact worldwide. The following scientific works were prepared during this project execution: “Polymorphisms in Glucose-6-phosphate dehydrogenase deficiency and different haemoglobinopathies in Blagoevgrad region” by De. D. Toncheva; “Glucose-6-phosphate dehydrogenase deficiency in blood donors” by Dr. D. Mavrudieva; “Analysis of some blood genetic markers in Middle Rodopa population” by De. St. Lalchev; “Clinical and genetic polymorphisms of Glucose-6-phosphate dehydrogenase deficiency and the abnormal haemoglobins” by Dr. M. Nacheva. 3. Analysis of the polymorphisms in the degenerative neurological disorders in Bulgaria. This research was established by Dr. M. Abadjiev from the Department of Neurology at the Institute for Specialization and Improvement of Doctors and followed by research of the Department of Medical Genetics with principal investigator Dr. M. Tzoneva. In 1980 and the following decade the scientific interests of the Department of Medical Genetics were expanded and focused on the analysis of the clinical and the genetic polymorphisms in human genes and chromosomes. Research projects in this area were performed in collaboration with different clinical departments and clinics of gastroenterology, nephrology, cardiology, ophthalmology, urology, ect. Among the clinically relevant results from this work was the discovery of chromosome marker in Balkan Endemic Nephropathy (D. Toncheva, Ts. Dimitrov, M. Tsoneva, the names of the authors are entered in the Golden Book of Bulgarian founders and inventors of the Bulgarian Patent Office) and discovery No 11 "Differences in the degree of involvement of genetic factors in patients with hypertension as main pathogenetic mechanism of hypertension - volume and vasoconstructive (Elenkova A. K. Boyanov, D. Vasileva, H. Vaskova, M. Mavrudieva). Original studies are conducted under the guidance of Prof. Maria Tsoneva by Dr. Petranka Ilieva "Immunogenetic studies in ulcerative disease" (1982, PhD thesis), Dr. Varban Ganev "Genetic factors of male infertility" (1987), Dr. St. Slavchev "Genetic studies in patients with ischemic heart disease after a myocardial infarction" (1988, PhD thesis), Dr. F. Filipov "Hereditary and congenital diseases of the eye in the etiology of infant blindness and its prevention" (1979), Dr. R. Markova "Dermatogliphic trials in patients with congenital heart malformations" (1981), Dr. A. Popova "Clinical and genetic forms and variants of child eye patlogy leading to blindness" (1994). Clinical and genetic studies of the frequency and type of the mutant forms of Pi system encoding the synthesis of alpha-1-antitrypsin and their role in the development of COPD, chronic ultsero-haemorrhagic colitis, liver cirrhosis, chronic hepatitis, chronic pancreatitis have been conducted. Clinical and genetic polymorphism was studied at chromosome level in Bulgarian population after the introduction of the new banding staining techniques. Further details for the link between the C-heterohromatin areas and the physiological and biological indicators and pathological conditions have been received. Sister chromatid exchanges (SHE) were implemented as a test for mutagenicity. Chromosome polymorphism was a joint development project with the Institute of Medical Genetics in ANSSSR,Prof.A.Zaharov. In this period many new and interesting practical casus and scientific surveys designed to help the quick introduction of genetics in health care practice have been published. In the third decade (1989-2000) the Department conducted research projects funded by local and international funds in cooperation with the Department of Neurology, Psychiatry, Clinical Pharmacology, Surgery, Nephrology, Laboratory of Molecular Pathology in “Maichin Dom” hospital, National Center of Oncology, National Center of Radiobiology and Radiation Protection, Institute of Genetics at BAS and others. The role of genetic polymorphism in pharmacogenetic defects was studied in two joint projects between the Department of Clinical Pharmacology (Coordinator Prof. Vitan Vlahov) and Department of Medical Genetics (under the scientific direction of Prof. D. Toncheva) – “Genetic mechanism of the metamizole induced agranulocytosis”, Fund “Scientific Research”, Ministry of Science and Education, Bulgaria, Contract No 867/19.05.1997 and «Genetic polymorphism of CYP2D6 and individualized treatment with antidepressants and neuroleptics». The project «Cytogenetic studies on chromosome fragility and unstable locus associated with schizophrenia»; Fund Research, Ministry of Education and Science, Bulgaria, Contract N 614/1996 (1996 - 1999, Project Manager Assoc.Prof. Toncheva) determined high incidence of fragility in chromosomes 3, 20 and 22, a prerequisite for detailed molecular-genetic studies that are ongoing. The role of the low-frequency chromosomal mozaicism in patients with unsuccessful in vitro fertilization was studied by Prof. D. Toncheva in connection with a Bulgarian-Greek in collaboration with the Department of Biology, MU Sofia. Studies of the genetic polymorphism at DNA level were mainly in oncogenetics. Polymorphisms and mutations in p53 were investigated in patients with breast cancer, together with the Institute of Genetics at BAS and the National Center of Oncology. This project set the basis to create the register of familial forms of the disease. The joint studies with the Departments of Neurology and Obstetrics and Gynecology were related to the investigation of the genetic characteristics of neurofibromatosis type I and II. Following the project “Induced mutagenesis” in 1995-1998 was established an important international project “Development and implementation of biomarkers for the assessment of the risk related to the exposure to genotoxic chemicals” with financing from the European Community, program Copernicus. Project coordinator was Prof. A. Kapas from the Institute of Biology at the National Center for Scientific Research Democritis, Athens in collaboration with scientists from the Czech Academy of Sciences. High efficiency tests for reporting the chromosomal aberrations and micronucleoses in workers exposed to high or low doses of organic solvents and heavy metals have been reported. In the period 1995-1996 has been conducted a project “ Genotoxic action of the anesthetics halotan, dormicum and diprivan for people in terms of general anesthesia”, funded by the Scientific Fund of MU, Sofia. In cooperation with NTSRRB, we worked on the assessment of the health status of the population, settled around the sites of nuclear industry, evaluation of the effect of the anti- mutagenic effect of poly-vitamin preparations in workers from the Kozloduy Nuclear Power Plant and others. On projects of the Military Medical Academy, we conducted studies to evaluate the radiation sensitivity in persons and patients, exposed to ionizing radiation and to study the effect of some potential radioprotectors through cytogenetic markers. From 2000 to the research activity of the department developed through cooperation with leading genomic centers in the world (in Germany, Holland, England, Switzerland, France, Japan) with the University of Wales, College of Medicine, Department of Psychological Medicine UK; International Center of Genetic Engineering and Biotechnology, Triest; Institute Pasteur, France; The Stephan Angelov Institute of Microbiology, Bulgarian Academy of Sciences; Instituts Pasteur du Reseau; Laboratory of Molecular Medicine, Human Genome Centre, Institute of Medical Science, the University of Tokyo; Laboratory of Molecular Cytogenetics, Tokyo Medical and Dental University; Leiden University Medical Center, The Netherlands, Gerg-August-University Gottingen Stiftung Offentlichen Rechts Bereich Humanmedizin. Financed new national and international projects: 1. “Bulgarian Consortium For Structural Genomics And In Silico Drug Design” (No DRI-5/2006) 2. “Bulgarian Modern Genome Center for Common Diseases”. Bulgarian Ministry of Education and Science – Upgrading Of Research Infrastructure. Contract № 05/01.08.2005. 3. “DNA bank of patients with schizophrenia and Bipolar affective disorders”. Funded by Janssen Research Foundation (2000-2003). 4. “Epidemiology and Genetics of Urinary Tract Tumors in Patients with Balkan Endemic Nephropathy”. INCO-COPERNICUS, Contract № ERB IC15-CT98- 0318. 5. “Association study in a linkage region of schizophrenia using pooled DNA genotyping and family based controls”. ICGEB Trieste, Contract no CRP/04/025, 2005-2007. The final results of the project realization were estimated highly by the international reviewers. 6. COST Action Proposal on Urine and Kidney Proteomics, EUROKUP, BM0702 7. Diagnosis and prevention of hereditary diseases and predispositions" National Program of the Ministry of Health, 2000-2005 и 2008-2011. 8. Analysis of the microstructural aberrations in spontaneous abortions by tissue microarrays. 9. CYCLIN D1 amplification in colorectal cancer - frequency and clinical significance. ”. Contract № 39/2002, Medical University - София. 10. Association studies of catechol-O-metyltransferaze and beta-hydroxylase- candidate genes for schizophrenia and bipolar affective disorders. Contract № 10- D/2003, Medical University - Sofia. 11. “Genome-Wide Analysis of Gene Expression in Primary Sporadic Epithelial Ovarian Cancer” (Collaboration between NNHGCCDCD-MUS and Human Genome Center, Tokyo University. Funded by Tokushukai Co. and Human Genome Center, Tokyo University), Prof. Yusuke Nakamura) and Assoc. Prof. Draga Toncheva; 12. “Identification of Differentially Expressed Genes Related to Thyroid Carcinoma by cDNA Microarray”; (Collaboration between NNHGCCDCD-MUS and Human Genome Center, Tokyo University. Funded by Tokushukai Co. and Human Genome Center, Tokyo University), Prof. Yusuke Nakamura and Assoc. Prof. Draga Toncheva 13. “Genome wide association studies of bipolar disorders using a high throughtput SNPs typing system” (Funded by RIKEN Institute, Contract 2006) Prof. Yusuke Nakamura and Assoc. Prof. Draga Toncheva; 14. “High throughtput SNPs association study on schizophrenia” (Funded by RIKEN Institute, Contract 2006) Prof. Yusuke Nakamura and Assoc. Prof. Draga Toncheva; 15. Familial based collaborative research based on the genetic causes of this psychiatric illness between the Department of Medical Genetics and the University of Wales College of Medicine, Department of Psychological Medicine 2002-2004. 16. Molecular cytogenetic changes in bladder cancer. Collaborative study between Department of Medical Genetics and Basel University of Switzerland. 17. IPSS, International Pharmaceutical Strategies$Solutions, Consultant, Technology, Product Development "An open labelled Clinical Phase II Study with Cis-4-Hydroxyl-Proline (CHP) as an Anti-Tumour Agent in Patients with Colorectal Adeno-Carcinoma, Berlin, Germany 18. Tissue microarrays for analysis of molecular-cytogenetic aberrations in spontaneous abortions Contract N38/2002, Medical University – Sofia 19. CYCLIN D1 oncogene amplification in colorectal cancer - frequency and clinical significance. Contract N 39/2002, Medical University of Sofia 20. Characteristics and significance of the molecular-cytogenetic abnormalities in tumors of the upper respiratory tract. Contract No 12-D/2003, Medical University of Sofia, Council on Medical Sciences, D.Koynova 21. Association study of cathehol-O-methyltransferase and beta-hydroxylase candidate genes in major psychiatric illnesses - schizophrenia and bipolar affective disorders. Contract No 10-D/2003, Medical University of Sofia, Council on Medical Sciences, A. Dimitrova 22. Analysis of the copy number changes of the oncogenes PRAD1 and ZNF217 in clinicopathological ovarian tumors with different biological behavior and characteristics. Contract No 2 / 2004 Medical University of Sofia, Council on Medical Science. 23. Institute Pasteur, France; The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences; Instituts Pasteur du Reseau. 24. „D’etude de l’infection Papilloma et cancer sur le plan international” 25. “Interactions of Hepatitis viruses’ genotypes and/or variants with the environment evolution of their respective clinical and genetic impacts on primary liver cancer development in Central and Eastern Europe”. 26. Leiden University Medical Center, The Netherlands. “Molecular-cytogenetic analysis of head and neck tumors”, EUROGENDIS Program “The genetic basis of diseases” (2005-2006) 27. Gerg-August-University Gottingen Stiftung Offentlichen Rechts Bereich Humanmedizin, EUROGENDIS Program “The genetic basis of diseases” (2005- 2006) 28. Medical University, Council of Medical Sciences, Contract № 40 / 2007, Theme: Evaluation of the ovarian resource – ploidic analysis and analysis of the state of chromatin in ovocytes isolated from surgically extracted ovarian tissue. 29. MES, Science Fund, Contract VU-L-311 / 07. Topic: Study of the chromosomal and cytoskeleton defects in ovocytes and preimplantational embryos as major causes for the early embryonic loss in mammals. 30. Medical University, Council of Medical Science, Contract № 6 / 2007. Topic: Microdeletions of the Y chromosome in idiopathic azoospermia and acute oligospermia - pilot survey by DNA microarrays. 31. Medical University, Council of Medical Science, Contract № 5 / 2007 on "Comprehensive genomic scanning for microstructural unbalanced chromosomal aberrations in hemihyperplasia and Proteus Syndrome The scientific studies are directed into two main areas - molecular-genetic disorders in various diseases and genetic markers associated with polygenic diseases. Genetic studies have been conducted in Balkan endemic nephropathy, genetic disorders in malignancies, associative studies of major psychiatric illnesses, pharmacogenomics, population-genetic research, clinical and genetic studies and other chromosomal pathology and malformations. The main achievements of the department are: In the area of the genetic disorders in uroepithelial tumors: The type of genetic heterogeneity of uroepithelial tumors has been discovered – altogether 9 genes in the fragile locus of the tumor genome. Tumors can be connected with independent changes in the genes CDKN2A, CCND1 and ZNF217 or with combined aberrations. In the chromosome 11q13 region there is a coamplification of the genes CCND1, FGF3 / 4, FGF3 and EMS1, with the main gene CCND1. The progression of the uroepithelial tumors depends on the copy number changes (amplification and gain) of the oncogenes from the 11q13 amplicon and CMYC, from the genetic gain of ZNF217 and the amplification of ErbB1, but does not depend on the change in the normal number of copies of the tumor suppressor gene CDKN2A. A reduced tumor-specific survival of the patients with tumors of all stages in gain and amplification of genes from 11q13 amplicon • We have proved a free progression survival of patients with pT1tumors with changed number of gene copies (amplification and gain) in 11q13 amplicon and in gain of CMYC. In the Balkan endemic nephropathy: • For the first time the allele and genotype frequencies of polymorphic variants of enzymes metabolizing xenobiotics (phase I and II), of MDR1 (phase III), of TGFβ1 in patients with Balkan endemic nephropathy and in patients with BEN uroepithelial tumors have been defined. • A role of genotype * 2 / * 2 of NQO1 has been defined as a predisposition to BEN associated tumors. • Immunophenotyping of BEN patients has been carried on and we proved three groups of immune profiles. • A high concentration of neopterin in patients with BEN has been defined. • We proved the role of Bunyaviridae family viruses like the hantaviruses in etio- pathogenesis of BEN. • A hypothesis for the pathogenesis of the uroepithelial tumors associated with BEN has been suggested. • A large-scale screening to detect new variants in the coding and non-coding sequences and promoter regions of 18 candidate genes for psychiatric disorders, not analyzed so far has been carried on and 77 new variants were identified. Major psychiatric disorders The association of SH3BGR, MCG3329 and WRB genes, located in the 21q21.3-22.3 region, which is strongly linked to bipolar affective disorder, has been initially analyzed and the positive association of some alleles and haplotypes with the disorder has been proved. The variants in the protocadherin γ A gene cluster have been analyzed for the first time and the first genetic variant conferring protective effect in schizophrenia has been discovered. A hypothesis about the role of variations in the neurotransmitting genes, modulating molecular mechanisms in the main psychiatric disorders has been proposed. Laryngeal carcinoma We have found association of: the CCND1 amplification with the metastatic potential; the CCND1 amplification with the cell differentiation degree; the C-MYC gain with the tumor stadium; the C-MYC gain with the metastatic potential and the ZNF217 gain with the tumor stadium. From the combined analysis of ЕGFR, CCND1, C-MYC and ZNF217 genes, we determined genetic heterogeneity in the laryngeal tumors - 29.58% of which have normal gene copy number, whereas 70,42% have altered gene copy number. In laryngeal tumors with altered ЕGFR, CCND1, C-MYC and ZNF217 gene copy number, the genetic aberrations are associated with the metastatic potential and are involved in the transition from unengaged (N0) to engaged (N1-3) lymph nodes. In melanomas In skin melanomas, the gene amplifications of MYBL2, ZNF217, CYP24 and STK6 are found seldom, whereas the numerical aberration of chromosome 20 are common finding. For the first time, the combined alteration in C-MYC/CDKN2A in skin melanomas has been determined. Patients with С-MYC/CDKN2A melanoma nodules have higher survival rate than patients carrying only CDKN2A deletion. Laryngeal carcinomas differ from melanomas by the quite higher frequencies of CCND1 and C-MYC amplifications and lower ZNF217 gain frequencies. Ovarian carcinoma In respect of the whole genome instability inferred by the CGH microarray method, a statistically more significant higher frequency of unbalanced alterations in serous than in nonserous carcinomas has been determined. By virtue of the high resolution of the CGH microarray technology, for the first time, significant for ovarian carcinomas were discovered: 17q12-q24 amplifications, including LASP1 (17q12), TGF11 (17q21.32), MUL (17q23.2), TBX2 (17q23.2), AXIN2 (17q24.3) and GRB2 (17q25.1) oncogenes; 8q13.2 amplifications – clone RP11- 120n14; homozyguous deletions in specific clones 8p23.3 (1.35 Mb), 8p21.1 (27.62 Mb), 8p21.2 (26.29 Mb) and 8q21.2 (85.43 Mb), which eventually may contain potential tumorsupressor genes. Serous carcinomas are associated with genetic losses in 1p, 8p, 17p and 17q; gains in 1q32.1, 1q42 and 1q43 and gains in 8q11-q13 and 8q24. Nonserous carcinomas are associated with genetic losses in 1q23, 1q25, 1q32 and 1q43 and gains in 17q11.2, 17q12, 17q24 and 17q25. The genetic losses in 8p21.1, 8p23.3 and 8q21.2 are more frequently found in higher stage than in lower stage carcinomas. Approximately 70% of malignant ovarian carcinomas carry unbalanced alterations in the studied oncogenes. The alterations in c-myc and CCND1 are early events in ovarian tumorigenesis, while the alterations in Her2, EGFR and ZNF217 genes in 20q13.2 are late events in ovarian tumorigenesis. In benignant ovarian carcinomas, the frequency of molecular-cytogenetic aberrations in the analyzed oncogenes ranges from 0.75 to 7.8% and probably is due to precancerous lesions. Approximately 8% of the low malignant potential tumors carry molecular- cytogenetic aberrations characteristic for carcinomas. The erbB-1 and erbB-2 amplifications are associated with high degree of malignancy, but they do not show associations with the tumor phenotype. The unbalanced alterations in 20q13.2 are associated with progression of the stadium of the disease. The following associations of unbalanced alterations with the histological subtype of the tumors have been determined: Her2 amplification with giant cell carcinoma and their tumor degree; CCND1 amplification with mucous carcinomas; c-myc amplification with endometrial carcinoma and their stage. Contributions with practical significance: 1. Bulgarian collection of tissue microarrays of uroepithelial tumors has been constructed. 2. The largest in the world to date DNA bank, containing DNA samples from parents and probands with schizophrenia, bipolar affective disorder type I and schizoaffective disorders has been constructed. 3. DNA pools of bipolar affective disorder type I patients and their parents have been composed; their efficiency and capability for future wide usage in polymorphism screening has been proven. 4. A plan for analysis or uroepithelial tumors for determination of their genetic heterogeneity has been proposed. Two types of microarrays have been constructed – tissue microarray containing 280 skin melanomas from Bulgarian patients and tissue microarray containing the most representative sample reported in literature to date, which comprises 1385 laryngeal carcinomas. An analysis of combined and single alterations in EGFR, C-MYC, ZNF217 and CCND1 in 240 laryngeal carcinomas, successfully hybridized for the four genes has been provided for the first time. The frequencies of increased copy number of genes in 20q13 region (ZNF217, CYP24, STK6 and MYBL2) in skin melanomas have been analyzed for the first time. The combined alterations in CDKN2A/C-MYC in primary melanoma nodules have been analyzed and their importance for tumor size, metastatic potential and survival rate has been evaluated for the first time. A detailed analysis of genomic disbalance on chromosomes 1, 8 and 17 with CGH microaarays, which contain 887 clones covering their entire length of the aforementioned chromosomes and have 1 ВАС clone/0.8 Mb average density, has been initially performed. The strongest candidate oncogenes in 17q12-q24 region in ovarian cancer have been initially identified. The amplification in 8q13.2 in ovarian carcinoma has been determined for the first time. The molecular-cytogenetic aberrations in benignant ovarian carcinoma have been initially identified. Associations of amplifications of Her2, CCND1 and c-myc oncogenes with some histological types of ovarian carcinoma have been identified for the first time. Prof. Draga Toncheva was supervisor of the PhD thesises of Dr. Dobrin Konstantinov: “Diagnostics and prognostic role of some cytogenetic and molecular- cytogenetic findings in acute leucosis in childhood” (2002), (Prof. D. Bobev, Assoc. Prof. D. Toncheva), Boriana Zaharieva “Characteristic and importance of the molecular-cytogenetic aberrations in uroepithelial tumors” (2003), Srebrena Atanasova “Factors causing hereditary predisposition for uroepithelial tumors in Balkan endemic neuropathy (BEN)” (2003), Lyudmila Georgieva “Family-based association studies of genetic markers in Bulgarian schizophrenic patients” (2003) (PhD supervisors: Assoc. Prof. Draga Toncheva, Prof. M. Owen), Albena Dimitrova “Familial molecular-genetic association studies of bipolar psychoses” (2004) (PhD supervisors: Assoc. Prof. Draga Toncheva, Assoc. Prof. G. Kirov), Ralitsa Zhivkova “Human egg cells and zygotes: ploidic and pronuclear status of unsuccessful in vitro fertilizations” (2005) (PhD supervisors: Assoc. Prof. I. Vatev, Assoc. Prof. Draga Toncheva), Stefka Delimitreva “Cell and nuclear destruction and chromosomal defects in preimplantational human embryos” (2005) (PhD supervisors: Assoc. Prof. I. Vatev, Assoc. Prof. Draga Toncheva), Dr. Milena Velizarova “ Cytogenetic and molecular- cytogenetic aberrations in acute leukaemias in adulthood” (2006) (PhD supervisors Prof. M. Penev, Assoc. Prof. D Toncheva), Dr. Ivanka Dimova “ Characteristic and importance of the molecular-cytogenetic aberrations in ovarian tumors” (2006), Denitsa Koinova “Analysis of genetic alterations in unstable chromosomal loci in two types of tumors – laryngeal carcinomas and skin melanomas” (2006). At the moment, Prof. D. Toncheva is supervisor of the PhD thesises of: Irina Zaharieva, Darinka Petrova, Dragomira Nikolova, Elitza Becheva, Radoslava Vazharova, Daniela Avdjieva, Tatiana Milachich, Sena Kuman Karachanak, Svetlana Metodieva, Lyubomir Getov, Radostina Cherneva. In summary, under the supervision of the lecturers at the Department of Medical Genetics, 28 candidate dissertations (PhD degree nowadays) and one Doctor of Science degree (Assoc. Prof. D. Toncheva) have been successfully completed and defended. Awards to the members of the Department In 2005, Boriana Zaharieva won the competition for the best young scientist “Acad. Asen Hadjiolov”. In 2003, Zaharieva also won the first award for the best scientific worker at the Institute of Experimental pathology and morphology of BAS. She has specialized in the field of molecular genetic methods (PCR, RFLP) in Ireland; molecular cytogenetics (fluorescent in situ hybridization – FISH and comparative genomic hybridization – CGH) in Austria and the tissue microarray method in Switzerland. In 2006, Dr. Ivanka Dimova won the best young scientist award “Acad. Asen Hadjiolov”. Assoc. Prof. Draga Toncheva won the “Academician Dimiter Orahovats” award of the Medical faculty for great achievements in scientific and tutorial activity (2004), medal 90 years of Medical faculty –Sofia, honorable medal of the Romanian genetic foundation "Foundation for the Promotion of Genetics" (2000), honorable sign of Tokyo medical and dental university. International specializations of the members of the Department Over 40 short-term and long-term specializations of young scientists have been performed: Dobril Ivanov. University of Wales, College of Medicine Cardiff, UK; Molecular- genetic analyses of early-onset psychoses, 2002; Lyudmila Naichova Georgieva. Real-time PCR, Antisel Selidis Bros, Bulgaria LTD; Lyudmila Naichova Georgieva. University of Wales College of Medicine Cardiff, UK., by the student exchange programme “Socrates Erasmus” (May-September, 2001); Lyudmila Naichova Georgieva. University of Wales College of Medicine Cardiff, UK., by the European Scientific foundation “Integrated approaches for functional genomics”, founded by the European community (April-December, 2002); Lyudmila Naichova Georgieva: Human Genome Project qualification course (Human Genome Mapping Project) - Introductory Molecular Biology Computing Course 23-25 July 2001, Cardiff; Lyudmila Naichova Georgieva: Human Genome Project qualification course (Human Genome Mapping Project) – Sequencing Project Management Using Staden Package) 20-21 August 2001, Cambridge; Albena Dimitrova. University of Wales College of Medicine Cardiff, UK., by the student exchange programme “Socrates Erasmus” 2003; Boriana Mihailova Zaharieva – four months specialization in 1998 molecular cytogenetics (fluorescent in situ hybridization FISH and comparative genomic hybridization CGH) at The Children's Cancer Research Institute at hospital “St. Anna” in Vienna, under the supervision of Prof. Pscar Haas and Prof. Peter Ambros. Austrian Ministry of Education and Transport Fellowship; in 2001, Boriana Zaharieva specialized on tissue microarray technology for two months at the Institute of pathology, University in Basel, Switzerland. Mutual collaborative project between the Department of Medical genetics and the Laboratory of molecular pathology at the Institute of Pathology, University of Basel; in November 1999, Boriana Mihailova Zaharieva participated in the workshop for constructing tissue microarrays (TMA) at the Institute of Pathology, University of Basel, Switzerland; in 1997, Srebrena Yaneva Atanasova participated in "TEMPUS" course at the Medical university of Sofia; in 1999, Srebrena Yaneva Atanasova participated in one-week practical course entitled “PCR-based methods for detection and characterization of hereditary, malignant and infectious diseases” FEBS Advanced Course No 99-16, Macedonian Academy of Sciences, Skopje, Macedonia; Srebrena Yaneva Atanasova - 2001-2002 EUROGENDIS Program “The genetic basis of diseases” of the Maria Currie Foundation, Department of Clinical chemistry, Georg-August- University, Gottingen, Germany; Srebrena Yaneva Atanasova - 2003-2006 Department of Clinical chemistry, Georg-August-University, Gottingen, Germany; Radoslava Vazharova – 2-8 December 2002, The Fifth Framework Programme project, Institute of experimental genetics, Prof. Sram, Prague, Czech Republic; Ivanka Dimova - Practical course “VYSIS FISH Application, operation and troubleshooting” – Wiesbaden, Germany, 7-10 April 2003; Ivanka Dimova - Pasteur’s international training course on molecular biology applied to the detection and typing of microorganisms – The Stephan Angeloff Institut of Microbiology, Sofia, Bulgaria, 6-14 November 2003; Ivanka Dimova - “Novel Strategies for Cancer Therapeutics and Diagnosis” – Montpellier, France, 31 October 2004 – 29 April 2005, TMR Marie Curie Research Training Grant, Contract No QLGA-CT-2000-60005; Denitsa Koinova. „Course Basic and Translational Oncology, Leiden University Medical Center, The Nederlands.” (28 November – 2 December 2005); Denitsa Koinova. „Course Biomedical Research Techniques IV, Leiden University Medical Center, The Nederlands. (26-30 September 2005); Darinka Petrova - Maria Currie Fellowship, EUROGENDIS Program “The genetic basis of diseases” Gerg-August-University Gottingen, “Monitoring of genetic alterations in malignancies”, 1 October 2004-1 October 2005; Scholarship from Gerg-August- University Gottingen Stiftung Offentlichen Rechts Bereich Humanmedizin, “Training in proteomics and cDNA microarray technologies”, 1 October 2005-1 October 2006; Dragomira Nikolova - “Identifying of Differentialy Expressed Genes Related with Thyroid Carcinoma by cDNA Microarray”, Human Genome Center, Tokyo University, 2006; Draga Toncheva. Human Genome Center, Tokyo University, 2006; Irina Takova Zaharieva. Socrates-Erasmus Program, in Cardiff, 14 April – 30 September 2006; Irina Takova Zaharieva. University of Wales College of Medicine Cardiff, UK., by Socrates-Erasmus student exchange Program, 14 April – 30 September.2007; Ivanka Dimova, Montpellier, France, 2007; Adelina Yosifova 2007, Riken, Japan; MD Elitza Becheva, 2007, Riken, Japan; MD Vazharova, 2007, Cambridge, UK; MD Dimova, 2007, Cambridge, UK; Adelina Yosifova, Genome wide association study of Bipolar disorder using a high throughput SNP typing system, Riken, Japan, 2007, Adelina Yosifova, Fine mapping of genes for association with schizophrenia, Riken, Japan, 2008 and others. The Department was publishing the international journal “Balkan Journal of Medical Genetics” for three years (1999-2001), the main editors of which were D. Toncheva and G. Efremov, but since 2002 the editor's office was transferred at the Macedonian academy of sciences and arts. The team of the Department has published over 150 articles in international journals with high impact factor, such as: “Genomics”, “Psychiatric Genetics”, “Obstetrics and Gynecology”, “Acta Psychiatrica Scandinavica”, “Journal of Nephrology”, “J Pathol. Kidney Int”, “Urologia Internationalis”, “Nephron Exp Nephrol”, “Clinical Biochemistry” and others. We have been involved in over 200 Bulgarian and international scientific quorums. The Department was ranked second at the Medical faculty, Sofia by individual impact factor per person. Other university sections in Bulgaria, teaching Medical Genetics 1. Medical university – Varna At the Department of Biology at the Medical University – Varna, Medical Genetics sector was formed, which under the guidance of Prof. Maria Tsoneva introduced medical genetics training (lectures and practical exercises) for the first time in Bulgaria, in 1969, in IX semester for medical students. From 1982 to 2005 head of the sector and lecturer was Associate Prof. L. Vassileva, and since 2005 Prof. L. Angelova.Between 1974 -1994 teaching, was held at the III semester with co- ordination program for all medical institutes.From 1996 until now it is held in VII semester with chorarium 60 hours. In recent years, It is hold an English speaking teaching for foreign students. Teaching is done by head of the sector and 2 assistants. From 2000 provide teaching of Medical Genetics of medical colleges in Varna, Shumen and Dobrich. Sector through its laboratory conduct cytogenetic diagnosis in patients with reproductive infertility , congenital abnormalities and oncohematological diseases. Since 2007 started the introduction of prenatal chromosomal diagnosis, and biochemistry screening in pregnant women. The Scientific Research are basically in the field of cytogenetics, clinical genetics and genetic counseling. 2. Medical University – Plovdiv Initially in 1967 was establishes a genetic laboratory to TSNIL, and from 1973 Genetically section with head Dr. G. Valkova. Later, in 1978 the section is included in a department of Biology, as a section of Medical Genetic with head associate Professor G. Valkova that with 2 assistants conducted the teaching of medical students of Medical Genetics in IV semestar with 28h chorarium and final exam. In the period 1971 - 1986 years running and cytogenetic diagnostic laboratory at the Department of Pediatrics, led by associate Professor E. Genev. From 1987 is form Medico- genetic consultative Centre (MGKTS) consolidating laboratories and MGK cabinets. The Center continues teaching in Medical Genetics at the same chorarium. Since 1993 teaching Medical Genetics is moved in VII semester with an increased chorarium of 60 hours and a final exam. From 2000 MGKTS enters as a section of Medical Genetics at the Department of Pediatrics and medical genetics, but by 2004 is formed self Department of Medical Genetics with laboratory sector to University Hospital with head associate Professor M. Stefanova. Diagnostic- advisory work during this period include basically cytogenetic diagnosis and genetic counseling, as in recent years was introduced prenatal chromosomal diagnosis in pregnant and modern molecular-genetic methods for diagnostics mikrodeletion syndromes. The Scientific Research work during this period is focus on population genetics, clinical cytogenetics and experimental mutagenesis. 3. Medical University – Pleven From 1976-1977 year to the Department of General Biology creating cytogenetic laboratory with medical and genetic counseling later formed as a section of Medical Genetics. Since 1987 the section was transformed into Medico-genetic Advisory Center (MGKTS) and in 1997 is Department of Medical Genetics until 1999 when they merged in a general Department of microbiology, virology and medical genetics. Teaching of Medical Genetics was introduced in 1976 in V semester with 28h chorarium and final exam. In the period of 1976- 1989 the lectures was consecutively read by associate Prof. M. Abadjiev and associate Prof. V. Georgieva from the Department of Medical Genetics in Sofia. From 1989 teaching was taken by associate Prof. M. Simeonova and 2 assistant. In 1995 the education program was updated with 56 h chorarium, and final examination during the educational year 1999/2000 and introduces the English speaking teaching for foreign students. From 2004 chorarium was increased to 60h. Since 1997 teaching of medical genetics has taken in medical colleges in Pleven, Russe and Veliko Tarnovo. Parallel with teaching work is realize laboratory diagnostic activities- cytogenetic diagnosis, genetic counseling, and regional Register of congenital abnormalities. The Scientific Research initially was in the field of population genetics, genetic monitoring, clinical genetics and later in problems with mental retardations. 4. Medical faculty in TU- Stara Zagora In 1983 in the Department of Biology was formed Department of Medical Genetics led by Prof. T. Evrev, which together with 2 assistants began teaching in medical genetics in V semester with chorarium of 28 hours and final exam. In 1988 the sector was reorganize in the Medico-genetic Advisory Center (MGKTS) and in 2000 it is again sector to the Department of Molecular Biology, immunology and medical genetics. From 1989 to present lecture course and final examination is conducted by associate Prof. St.Lalchev by the Department of Medical Genetics, Sofia. From 1994 chorarium is increased to 60h and was introduced a final exam. Since 1997 the section conducted teaching in medical genetics in medical colleges in St. Zagora, Haskovo, and Sliven. Diagnostic work includes mainly prenatal cytogenetic analysis and genetic counseling. The Scientific Research is focus on experimental mutagenesis and genetic monitoring of risk occupational groups.
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