Department of Medical Genetics_eng_deinost by nuhman10

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									                      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
        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

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,
        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,
        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
        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

        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
        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,
        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,
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
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
   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
       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
2. “Bulgarian Modern Genome Center for Common Diseases”. Bulgarian Ministry
   of Education and Science – Upgrading Of Research Infrastructure. Contract №
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-
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
    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
   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
   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
               EUROGENDIS Program “The genetic basis of diseases” (2005-
    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
      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
      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
      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
      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
       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
       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

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

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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