4^th World Congress on Human Genetics and Genetic Diseases April 19-20, 2018 Dubai, UAE

Biography:

Korbinian Grote is a Senior Scientist at Genomatix AG. His expertise is in bioinformatics of gene regulation, neural networks and deep learning. For BLUEPRINT he coordinated the project activities at Genomatix which included the development of a processing pipeline for various omics data and the creation of a visual interface to allow non-bioinformaticians easy access to the data in a biological context.

Abstract:

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with about 2 – 2.5 million new cases per year worldwide. Only 27% of patients  survive 5 years or more after being diagnosed with the disease. [1]

Within the EU-funded BLUEPRINT project (http://www.blueprint-epigenome.eu) several epigenetic markers as well as expression data were generated from blood and bone marrow samples of several AML patients.

We have used DNase-Hypersensitivity and expression data from the project to identify putative transcriptional regulators and regulatory regions by combining omics data with literature. The approach included identifying DNase-HS regions that were common among AML patients, but absent in samples from healthy individuals. We then used RNA-Seq data from the project to identify transcription factor binding sites that were differentially regulated between the case and control group. Finally we used Genomatix' MatInspector software to pick regions that had both differences in DNase-HS as well as putative binding sites for the differentially expressed transcription factors. Potential target genes were selected by a next-neighbour approach and the findings were evaluated based on gene disease associations from Genomatix' literature database

Biography:

Bradford Wilson is a geneticist with over a decade of experience in DNA sequencing, bioinformatics, and genomics research. Dr. Wilson has conducted research in breast and prostate cancer, hypertension, and pharmacogenomics at the National Human Genome Center and the W. Montague Cobb Laboratory at Howard University. His approach to identifying the genetics underlying the biology of health disparities leverages genetic diversity and utilizes sequence variation to elucidate the pathophysiology

Abstract:

Opioid use disorder (OUD) and the associated increase in overdose deaths has become a U.S. national health priority. Medication-assisted therapy (MAT) is a treatment approach commonly used in OUD management. Buprenorphine, a partial mu-opioid receptor agonist and kappa-opioid receptor antagonist, has been shown to be an effective MAT option for OUD management. Buprenorphine is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. The CYP3A4*1B allele confers an ultrarapid metabolizer phenotype and is found at a significantly higher frequency in African populations compared to non-African populations. This genetic difference in CYP3A4 metabolism leaves some patients being managed on buprenorphine undertreated and at an increased risk for relapse. Clinical pharmacogenomics (CPGx) testing of CYP3A4 has been shown to improve MAT outcomes in African American patients. PGx-guided buprenorphine dosing reduced the number of relapses on OUD patients exhibiting the CYP3A4*1B genotype. Reduced relapse translates into additional downstream benefits including reduction in risk of Hepatitis C and/or HIV infection. The functional significance and clinical utility of this variant demonstrate the need for diversity in CPGx studies and pharmacogenomics testing algorithms.

Recent Publications:

1. Opioid Metabolizing Enzyme Allele Frequencies and Drug use in a Cohort of African American Young Adults. Bradford D. Wilson, Earl B. Ettienne, Victor Apprey, Adaku Ofeogbu, Muneer Abbas, Georgia M. Dunston, Forough Saadatmand ARC Journal of Addiction 2017 2: 4-9
2. Public choice theory and rhetoric: Advancing pharmacogenomics through health policy in Africa. Earl Ettienne, LP.D., MBA, RPh, Adaku Ofoegbu, PharmD, Mary Maneno, PhD, La’Marcus Wingate, PhD, Georgia Dunston, PhD, Philip Kurian, PhD, Bradford D. Wilson, PhD, KevinNguyen, Ginikannwa Ezeude, Jeronimo Augusto, MHSA African Journal of Rhetoric 2017 9: 119-142
3. Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach. Earl B. Ettienne, Edwin Chapman, Mary Maneno, Adaku Ofoegbu, Bradford Wilson, Beverlyn Settles-Reaves, Melissa Clarke, Georgia Dunston, Kevin Rosenblatt. Addictive Behaviors Reports 2017 Dec; 6: 8–14
4. Next generation sequencing reveals high prevalence of BRCA1 and BRCA2 variants of unknown significance in early-onset breast cancer in African American women. Luisel J Ricks-Santi, PhD; John Tyson McDonald, PhD; Bert Gold, PhD; Michael Dean, PhD; Nicole Thompson, MS; Muneer Abbas, PhD; Bradford Wilson, PhD; Yasmine Kanaan, PhD; Georgia Dunston, PhD. Ethnicity and Disease. 2017 Apr 20:27(2):169-178
5. Genetic polymorphisms in the serotonin receptor 7 (HTR7) gene are associated with cortisol levels in African American young adults. G Swanson, S Miller, A Alyahyawi, B Wilson, F Saadatmand, C Lee, G Dunston, M Abbas. F1000 Research 6:19 · January 2017

Biography:

Mouza Mohammed AlFashti AlAleeli received her Bachelor's degree in Medical Laboratory Science with Distinction with Highest Honor from Sharjah Higher Colleges of Technology, UAE, in August 2015. She worked for the ministry of presidential affairs as a medical laboratory scientist at Sheikh Khalifa General Hospital in Ajman, UAE, since December 2015. She is currently a member of the infection prevention and control committee of Sheikh Khalifa Medical City-Ajman and a member of the laboratory quality team of Sheikh Khalifa Medical City-Ajman. She had an experience of five months working on Mitochondrial DNA Testing in the police forensic laboratory in Sharjah, UAE. Her current research “The Significance of Applying Mitochondrial DNA Testing in Degraded Biological Evidence For The Identification of UAE Nationals to Aid in Forensic Analysis” leads her to discover the “Skipping Generations” phenomenon

Abstract:

Statement of the Problem: The demanding need to discover someone’s identity is not possible with the nuclear DNA especially when the traces are highly degraded, since the nuclear DNA is destroyed in these conditions. Only the mitochondrial DNA that is  inherited maternally can survive in these compromised conditions. The purpose of this study is to find a genetic commonality between UAE nationals.

Methodology & Theoretical Orientation: 150 buccal swabs of unrelated UAE female students (approved by the UAE ID) of Sharjah Higher Colleges of Technology were collected and kept at room temperature for a period of three months or longer; to destroy the nuclear DNA, so only the mtDNA is present. mtDNA testing was performed on these buccal swabs, and it’s consisting of DNA Extraction, Real-Time quantitative PCR, Cycle sequencing and Capillary electrophoresis. The ABI PRISM®310 Genetic Analyzer capillary autosequencer [ABI PRISM® SeqScape® Soft-ware Version 2.6] was used to generate the mitochondrial DNA profiles.

Findings: From these haplotype data, a total of 229 polymorphisms were observed carefully. 106 different polymorphisms were identified out of them, and classified into unique and common polymorphisms. Interestingly, two individuals from the study subjects lacked unique polymorphisms.

Conclusion & Significance: It’s impossible for anyone to preserve their mtDNA from their great ancestors till now. The discovery of the remains of the Romanov family back in 1991concluded that the comparison of mtDNA that is more than three generations old is more likely to get at least one mutation in the current generation. Therefore, if a vertical study is done on those two individuals with their older generations, definitely they will have unique polymorphisms compared to their older generations. Those two individuals are the effect of “Skipping Generations” phenomenon, the term that I have invented to solve the mystery of having two individuals with no unique polymorphisms

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Biography:

Abstract:

Hearing loss is a debilitating disorder that impairs language acquisition, resulting in disability in children and potential isolation in adulthood. Its onset can have a genetic basis, though environmental factors which are often preventable can also cause the condition. The genetic forms are highly heterogeneous and early detection is necessary to arrange appropriate patient support. Here we report the molecular basis of hereditary hearing loss in a consanguineous family with multiple affected members from Oman. Combining homozygosity mapping with whole exome sequencing identified a novel homozygous nucleotide substitution c.575T>C in the lipoma HMGIC fusion partner-like 5 gene (LHFPL5), that converted the 192nd amino acid residue in the protein from a leucine to a proline, p.(Leu192Pro). Sanger sequencing confirmed segregation with the disease phenotype as expected for a recessive condition and the variant was absent in 60,706 subjects from various disease-specific and population genetic studies as well as 50 unrelated individuals of Omani ethnicity. This study, which describes a novel LHFPL5 mutation in a family of Omani origin with hereditary hearing loss, supports previous clinical descriptions of the condition and contributes to the genetic spectrum of mutations in this form of deafness. This is the first report of a family from the Arabian Peninsula with this form of deafness

Biography:

Sayyed Morteza Hosseini (DVM, PhD) is associated professor and senior researcher at Department of Embryology, Advanced Center for Biotechnology, Dubai, UAE. His studies have focused on the molecular and cellular aspects of reproductive biotechnology, epigenetic reprogramming and developmental reprogramming. he has authored more than 70 publications and has been involved in different projects on animal cloning and transgenesis for production of pharmaceutical drugs and also transplantable organs

Abstract:

Without any doubt, regenerative medicine is the major innovation in health care because of its great capacity to repair or replacement of damaged/diseased human cells, tissues or organs to restore normal function. Despite past limited success in the clinical translation of several promising preclinical results, the spectacular recent progress in the field of stem cells and somatic cell nuclear transfer (SCNT) technologies has laid the promising foundation for cell based therapies of disease which cannot be cured by conventional medicines. 

The rapid advancement of stem cells technology can be illustrated by the progression of human embryonic stem cells (hESCs), induced pluripotent stem cells (iPS) and the use of pluripotent vs. somatic and of allogenic vs. autologous stem cells for a series of cell based therapies which have received Food and Drug Administration (FDA) approval and are now commercially available. On the other hand, the rapid advancement of SCNT technology can be illustrated by technical improvements, development of human and monkey cloned embryos and ESCs thereof as well as disease modeling and production of new lines of genetically modified cloned animals for xenotransplantation. Here, these advances and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be reviewed. The popular view and the ethical issues will be addressed and finally, the perspectives, challenges and directions for the future of regenerative will be discussed.

Recent Publications :

1. Lee SE, Hyun H, Park MR, Choi Y, Son YJ, Park YG, Jeong SG, Shin MY, Ha HJ, Hong HS, Choi MK, Im GS, Park EW, Kim YH, Park C, Kim EY, Park SP (2017) Production of transgenic pig as an Alzheimer's disease model using a multi-cistronic vector system. PLoS One 6;12(6).
2. Liu Z, Cai Y, Wang Y, Nie Y, Zhang C, Xu Y, Zhang X, Lu Y, Wang Z, Poo M, Sun Q (2018) Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer. Cell [Epub ahead of print].
3. Yao X, Liu Z, Wang X, Wang Y, Nie YH, Lai L, Sun R, Shi L, Sun Q, Yang H (2018) Generation of knock-in cynomolgus monkey via CRISPR/Cas9 editing. Cell Res  [Epub ahead of print].
4. Tachibana M, Amato P, Sparman M, Gutierrez NM, Tippner-Hedges R, Ma H, Kang E, Fulati A, Lee HS, Sritanaudomchai H, Masterson K, Larson J, Eaton D, Sadler-Fredd K, Battaglia D, Lee D, Wu D, Jensen J, Patton P, Gokhale S, Stouffer RL, Wolf D, Mitalipov S (2013) Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 153:1228-38.
5. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-76.
6. Maoa AS, Mooneya DJ (2015) Regenerative medicine: Current therapies and future directions. PNAS 112: 14452-14459.

Biography:

Avni Santani, PhD, is the scientific director and has over seven years of experience in molecular diagnostic testing. She obtained her PhD at Texas A&M University and her clinical laboratory training in genetics at The Children’s hospital of Philadelphia. Dr. Santani holds specialty board certifications in Clinical Molecular Genetics and Clinical Cytogenetics. Her primary focus is on new test development and adoption of next generation sequencing technologies for diagnostic testing. Dr. Santani has experience in developing diagnostic tests for over 100 disease genes implicated in disorders such as hearing loss, epilepsy, Noonan syndrome, Rett syndrome, paraganglioma, neuroblastoma and others. Her training and experience make her an expert in a wide variety of genetic disorders, molecular biology applications and genomic

Abstract:

With the explosion of genomic information and novel gene discoveries, clinical laboratories are faced with critical challenges in facilitating sensitive data interpretation. In particular, laboratories are faced with developing strategies that can incorporate data in the interpretation of genetic variants and review variants over time.

Dr. Santani will share insights in the integration of NGS data in clinical diagnostics, using exome sequencing as an example. She will address the development of a comprehensive interpretation pipeline for exome sequencing, discuss challenges with data interpretation, and present case studies from the exome sequencing program at Children’s Hospital of Philadelphia

Biography:

Dr. Ghada Al-Kafaji is an Associate Professor of Molecular Genetics in the Department of Molecular Medicine and the Director of Personalized Medicine Master Program at the College of Medicine, Arabian Gulf University, Bahrain. She obtained her PhD degree in Molecular Genetics from King's College London, University of London, UK. Following her PhD, she worked in the UK as a Postdoctoral Research Fellow at the School of Medicine, King's College London, and as an Assistant Professor of Genetics at the College of Science, University College Kensington. Currently, she is involved in lecturing and tutoring undergraduate and graduate students and supervising graduate theses. She has abundant publications in the area of molecular genetics that have been cited over 150 times. She participated as an active member in many International Scientific Associations. She acted as a potential reviewer for many journals and received several certificates of excellence in reviewing scientific articles. She also received a number of awards for best presentations and outstanding work in regional and international conferences.

Abstract:

Mitochondria play important roles in cellular energy metabolism and reactive oxygen species (ROS) generation. Hyperglycemia-induced overproduction of mitochondrial ROS contributes to mitochondrial dysfunction and the development diabetic complication, including diabetic nephropathy (DN). We investigated changes in the mitochondrial DNA copy number (mtDNA-CN), gene expression of mtDNA-encoded subunits of electron transport chain (ETC) complexes and mitochondrial biogenesis in DN.

ROS production, mitochondrial function, mtDNA-CN, gene expression of mtDNA-encoded ETC subunits and mitochondrial biogenesis regulatory factors were analysed in human mesangial cells cultured for 1, 4, and 7 days in normal and high glucose in the presence and absence of manganese superoxide dismutase mimic (MnTBAP) or catalase. Additionally, mtDNA-CN was analysed in peripheral blood of type 2 diabetes (T2D) patients with normoalbuminuria, DN patients with microalbuminuria or macroalbuminuria and healthy control subjects.

In the renal cells, high glucose induced a significant increase in ROS production, which was accompanied by a progressive decrease in ATP. mtDNA-CN, expression of mtDNA-encoded genes and mitochondrial biogenesis were increased at 1 day in high glucose but were decreased at 4 and 7 days. Treatment of cells with MnTBAP or catalase during high-glucose incubation attenuated ROS production and all these changes. In the subject groups, peripheral blood mtDNA-CN was significantly lower in DN patients compared with T2D patients and controls, declined with the severity of DN, and showed a significant diagnostic ability to differentiate DN patients from T2D patients and healthy controls. Lower mtDNA-CN was independently associated with the progression of DN, negatively correlated with albuminuria and conventional risk factors of DN, and positively correlated with eGFR.

Our data show that defects of mitochondrial genome paly important role in DN. Protection of mitochondria from high glucose-induced ROS may provide a potential approach to retard the development of DN. Our data also propose the mtDNA-CN as a novel blood biomarker for the early diagnosis of DN and the significance of decreased mtDNA-CN as another risk factor in the development of DN.

Recent publications

1. Al-Kafaji G, AlJadaan A, Kamal A, Bakhiet M (2018). Peripheral blood mitochondrial DNA copy number is a potential new biomarker for diabetic nephropathy in type 2 diabetes patients. International Journal of Molecular Medicine. In press, Manuscript number: 204218.
2. Al-Kafaji G, Sabry MA, Skrypnyk C (2016). Time-course effect of high glucose-induced reactive oxygen species on mitochondrial biogenesis and function in human renal mesangial cells. Cell Biology International  40(1):36-48.
3. Al-Kafaji G, Sabry MA, Bakhiet M (2016). Increased expression of mitochondrial DNA-encoded genes in human renal mesangial cells in response to high glucose-induced reactive oxygen species. Molecular Medicine Reports 13(2):1774-80.
4. Al-Kafaji G, Golbahar J (2013). High glucose-induced oxidative stress increases the copy number of mitochondrial DNA in human mesangial cells. Biomedical Research International 2013:754946.

Biography:

Marlena Szalata works in biotechnology field with the main emphasis on transgenesis of animals and plants. She is involved in purification and characterization of recombinant proteins obtained in prokaryotic and eukaryotic systems like plants and animal bioreactors. Marlena Szalata has expertise in molecular diagnostics of human, animal and plants genes. Recently she is involved in analysis of methylation level of selected human, animal and plant genes.

Abstract:

Statement of the Problem:

Epigenetics involves studies of changes in gene expression not associated with changes at DNA sequence level. The best characterized epigenetic mechanism involved in control of gene expression is DNA methylation. Methylation of cytosines in CpG island within promoters usually causes gene silencing. In transgenic animals we are interested not only in introduction of transgene but also in its activity. We have prepared transgenic pigs for xenotransplantation purposes with decreased recognition by human immune system by introduction of the human HLA-E gene under elongation factor 1 alpha promoter (EF-1α). Activity of HLA-E transgene was already confirmed on molecular level and flow cytometry. The purpose of this study was evaluation of specific methylation of HLA-E transgene.

Methodology & Theoretical Orientation: Genomic DNA was modified by bisulfite conversion and PCR products were analysed using pyrosequencing method. The most important steps were DNA isolation and DNA bisulfite conversion. Pyrosequencing enabled quantification of the specific methylation level of transgene.

Findings: The total level of methylation of the HLA-E transgene promoter was approximately 90% (range 67-100%) and the HLA-E gene 73.79% (29-100%). The obtained results of the HLA-E transgene methylation were compared to the results of transgene expression, which showed that the level of transgene expression in transgenic animals was stable, regardless of pig generation. This suggest, that level of methylation of transgene promoter does not affect directly its biological activity estimated by flow cytometry.

Financed by National Centre for Research and Development (no INNOMED/I/17/NCBR/2014) within framework of INNOMED programme Development of an innovative technology using transgenic porcine tissues for biomedical purposes. Acronym MEDPIG.

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Recent Publications (minimum 5)

1. Cheung NKM, Nakamura R, Uno A, Kumagai M, Fukushima HS, Morishita S, Takeda H (2017) Unlinking the methylome pattern from nucleotide sequence, revealed by large-scale in vivo genome engineering and methylome editing in medaka fish. PLoS Genet 13(12):e1007123.
2. Gödecke N, Zha L, Spencer S, Behme S, Riemer P, Rehli M, Hauser H, Wirth D (2017) Controlled re-activation of epigenetically silenced Tet promoter-driven transgene expression by targeted demethylation. Nucleic Acids Research 45(16):e147.
3. Hryhorowicz M, Zeyland J, Słomski R, Lipiński D (2017) Genetically Modified Pigs as Organ Donors for Xenotransplantation. Molecular Biotechnology 59(9-10):435-44
4. Kimsa-Dudek M, Strzalka-Mrozik B, Kimsa MW, Blecharz I, Gola J, Skowronek B, Janiszewski A, Lipinski D, Zeyland J, Szalata M, Slomski R, Mazurek U (2015) Screening pigs for xenotransplantation: expression of porcine endogenous retroviruses in transgenic pig skin. Transgenic Research 24(3):529-536.
5. Nuo MT, Yuan JL, Yang WL, Gao XY, He N, Liang H, Cang M, Liu DJ (2016) Promoter methylation and histone modifications affect the expression of the exogenous DsRed gene in transgenic goats. Genetics and Molecular Research 15(3).

Biography:

Professor Ryszard Slomski, is a head of the Department of Biochemistry and Biotechnology at Poznan University of Life Sciences and Professor at Institute of Human Genetics of the Polish Academy of Sciences in Poznan. His main research focus on: 1) preparation of gene constructs containing human genes for expression in animal cells, including large animals and preparation of other gene constructs in prokaryotic and eukaryotic systems; 2) characteristics of novel human, animal and plant genes, 3) paternity and relationship testing based on DNA studies; 4) molecular diagnostics of Duchenne muscular dystrophy (DMD), familial polyposis of the colon (FAP), thyroid cancer and Crohn’s disease. Professor Slomski is involved in development of an innovative technology of biomedical applications for tissues of transgenic pigs, acronym MEDPIG and development of cannabinoid collection technology from hemp with low THC content as means of treatment of pain in cancer patients, acronym ONKOKAN

Abstract:

Statement of the Problem:

The growing shortage of available organs is a major problem in transplantology. The promising solution could be xenotransplantation, i.e., the use of cells, tissues and organs of domestic pig. However, xenogeneic transplantation from pigs to humans involves high immune incompatibility and a complex rejection process. The rapid development of genetic engineering techniques enables genome modifications in pigs that reduce the cross-species immune barrier. The purpose of this study is to develop the technology to use transgenic pigs for biomedical purposes. The Project is an alternative to studies using stem cells and work aiming at the production of artificial organs.

Methodology & Theoretical Orientation: Development of an animal breeding system and the collection of skin, valves and blood vessels from transgenic pigs. The project involves also production of polytransgenic pigs using reproduction biotechnology methods. Very important was development and characteristics of gene constructs preventing xenotransplant rejection and multiparametric characteristics of transgenic animals. Tissues of transgenic animals were used for treatment of human cardiovascular diseases using vessels and cardiac valve bioprostheses. Biological dressings were obtained from skin of transgenic pigs.

Findings: Important issues in production of transgenic animals are characteristics of transgene, transfection and cell transformation, detection of transgene integration, mapping of transgene, passing specific traits to the offspring, homozygote selection, analysis of transgene activity and function. Fully characterized transgenic animals carrying three or more modifications may be used as sources of skin, heart valves or vessels.

Conclusion & Significance: Transgenic animals were generated using traditional methods and new genome editing technologies. Tissues of transgenic animals used in experimental studies showed growing potential in use as alternative treatment of human. This work was supported by grant No. INNOMED/I/17/NCBR/2014 from the National Centre for Research and Development.

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Recent Publications (minimum 5)

1. Hryhorowicz M, Lipiński D, Zeyland J, Słomski R (2017) CRISPR/Cas9 Immune System as a Tool for Genome Engineering. Archivum Immunologiae et Therapiae Experimentalis 65:233-240.
2. Hryhorowicz M, Zeyland J, Słomski R, Lipiński D (2017) Genetically Modified Pigs as Organ Donors for Xenotransplantation. Molecular Biotechnology 59:435-444.
3. Kimsa-Dudek M, Strzalka-Mrozik B, Kimsa MW, Blecharz I, Gola J, Skowronek B, Janiszewski A, Lipinski D, Zeyland J, Szalata M, Slomski R, Mazurek U (2015) Screening pigs for xenotransplantation: expression of porcine endogenous retroviruses in transgenic pig skin. Transgenic Research 24:529-536.
4. Wilczek P, Lesiak A, Niemiec-Cyganek A, Kubin B, Slomski R, Nozynski J, Wilczek G, Mzyk A, Gramatyka M (2015) Biomechanical properties of hybrid heart valve prosthesis utilizing the pigs that do not express the galactose-α-1,3-galactose (α-Gal) antigen derived tissue and tissue engineering technique. Journal of materials science. Materials in Medicine 26:5329.
5. Cierpka L, Ryszka F, Dolińska B, Smorąg Z, Słomski R, Wiaderkiewicz R, Caban A, Budziński G, Oczkowicz G, Wieczorek J (2014) Biolasol: novel perfusion and preservation solution for kidneys. Transplantation Proceedings 46:2539-2541.

Biography:

Dr. Namrata Londhe has done her doctoral work in Human Molecular Genetics at Bhabha Atomic Research centre, Mumbai. She is currently working in Kokilaben Dhirubhai Ambani Hospital and Medical Research centre as an expertise in cytogenetics and FISH based assays in constitutional, hematological and solid tumors. During her academic and industrial tenure, she has worked on several cytogenetic and molecular biology techniques and has presented her work at several national and international conferences

Abstract:

Statement of the Problem: To elucidate the genetic component in patients with developmental delay (DD) through 5 year retrospective data analysis. After the initial workup by the pediatrician, the patients were referred to the department for cytogenetic and molecular testing.

Methodology & Theoretical Orientation: Most detrimental form of developmental delay is global DD which is presented as overall absence of the required milestone in the child including mental, cognitive as well as motor delay. The advent of cytogenetic and molecular biology techniques has been helpful in understanding the genetic etiology of these conditions. DD is affecting 1:150 children. Cases with following indications like Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder, Global DD, Pervasive Developmental Disorder, Pervasive Developmental Disorder-Not Otherwise Specified, Syndromic, Intellectual Disability, Learning Disability, Specific DD, speech delay etc. were all included in the data analysis.

Findings: A total of 199 cases (age ranging from 5 months- 22years) were studied. Cytogenetic analysis was performed on 142 patients and chromosomal abnormalities were observed in 8.5% (12/142) of the cases. FISH assays (For Praderwilli/angelman syndrome, Digeorge, etc) were performed in 59 cases, positive results were obtained in 3.3% (2/59). Molecular analysis (Fragile X analysis, Rett syndrome, etc) was done for 44 subjects. One case 2.4% (1/44) revealed an intermediate phenotype for Fragile-X studies. Chromosomal abnormalities were found in 8.4% (12/142) cases. This observations can be further classified as structural abnormalities in 66.7% (8/12), numerical  abnormalities in 25% (3/12) and a combination both abnormalities was seen in 8.3% (1/12) of the cases. Polymorphic variants were found in 4.2% (6/142) of the cases.

Conclusion & Significance: Cytogenetic and molecular tests could successfully elucidate the genetic components implicated in 7.5% of the total cases. As chromosomal analysis can detect the anomalies up to 5MB resolution, advanced techniques like Microarray studies would be more helpful in detecting the cryptic subtle rearrangements in unsolved cases

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Biography:

Serhat Seyhan was born in istanbul in 1987. He graduated from Cumhuriyet University faculty of Medicine in 2011. He completed Karadeniz Technical University medical genetic phd in 2016, which he started in 2012. He is currently working as a medical geneticist in Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital

Abstract:

Statement of the Problem:

Chronic myeloid leukemia (CML) is a hematopoietic malignancy originating from transformation of a hematopoietic stem cell. BCR-ABL gene that resulted from a translocation between chromosomes 9 and 22 is detected in the majority of CML patients. IL-3, IL-6 and IL-11 are cytokines that affects the development of myeloid cells. The aim of this study to evaluate the relationship between IL-3, IL-6 and IL-11 and CML development.

Methodology & Theoretical Orientation: This study was perfomed using peripheral blood from 33 patients followed in our hematology clinic at Karadeniz Technical University Medical School obtained with a diagnosis of CML. We get peripheral blood from 34 healthy people that examined in Karadeniz Technical University Medical Schools clinics. RNA was isolated from peripheral blood and cDNA is synthesized. Then cDNA expression analysis was performed. Findings: IL-3, IL-6 and IL-11 gene expressions significantly decreased in CML patients with high expression of BCR-ABL gene compared to healthy individuals. After major molecular response IL-3, IL-6 and IL-11 gene expressions increased compared with the initial diagnosis of CML.

Conclusion & Significance: According to the our results; increase of BCR-ABL gene expression in CML patients may provide the proliferation of neoplastic cells without effective IL-3, IL-6 and IL-11 gene expressions in normal hematopoiesis. Ä°nverse relationship in our CML patients are available between BCR-ABL expression and IL-3, IL-6 and IL-11 expressions. Studies for IL-3, IL-6 and IL-11 gene expressions are needed to determine the relationship with BCR-ABL expression level and to be used follow up of patients with CML

Biography:

Maya Gaiozishvili is PhD in biology. She is Assistant-Professor at department of genetics, Ivane Javakhishvili Tbilisi State University. The field of her interest is the personalized medicine, human genetics, exactly, aging and medical genetics. She is investigator in grant projects, which concerns investigation of some genes polymorphism in Georgian population, also genetic parameters in different diseases. By her participation was determined the polymorphism of genes involved in warfarin metabolism, in Georgian population. Also, was determined the types of mutations and epigenetic variability - namely the degree of heterochromatinization, during the aging, atherosclerosis, cardiomyopathy, breast and lung cancers, in Georgian population. In some cases, the possibility of correction of altered genetic parameters by different agents. The results of the study are published in scientific journals.

Abstract:

The glutathione S-transferase (GST) enzyme system constitutes a family of multifunctional enzymes which play an important role in biotransformation and detoxification of many different xenobiotic. Human cytosolic GSTs are polymorphic, and have ethnic-dependent polymorphism frequencies, and have been associated with several types of diseases. In the double-null variant of GSTM1 and GSTT1 are respectively associated with a higher risk of different forms of liver injury, cancer, cardiovascular diseases etc[1-3].

Comparisons between GST null genotype frequencies in the worldwide populations show different patterns in Asian, African, and European populations.

Some detailed studies of GST variants in various geographic regions can increase the knowledge about relationship between the ethnicity and the prevalence of certain diseases[4]. Thus, it becomes necessary to consider the genotypic differences for reducing the risk of anti-tuberculosis drug-induced Liver injury[5].

The aim of our research was to determine the polymorphism of GSTM1 and GSTT1 genes in Georgian population.

In the studies was be used peripheral blood samples obtained from individuals randomly selected groups. The GSTM1 and GSTT1 null genotypes was investigated with the help of an Ese-Quant tube scanner-by SmartAmp Method[6].

The study of GST genes polymorphism in Georgian population revealed that 88% of individuals have positive genotypes of GSTT1 and GSTM1, and 12% of individuals have null genotype only by one of this gene - GSTT1 or GSTM1.  Out of these, GSTT1(-) null genotype was observed in 4% of individuals and GSTM1(-) have 8% of individuals. It should also be noted that there was not observed double null genotype (GSTT1(-), GSTM1(-)) in investigated group of individuals.

In the next stage of our research we will investigate the relation between the null genotypes of GSTM1 and GSTT1 and risk of development drug-induced hepatotoxicity in TB patients from Georgianpopulation.

The results will play the most important role in personalized medicine, in the appointment and management of drugs and for prevention of adverse drug reactions   in patients of Georgian population.

Recent Publications (minimum 5)

1. Rafiee L., Saadat I., Saadat M. (2010) Glutathione S-transferase polymorphisms (GSTM1, GSTT1 and GSTO2) in three Iranian population. Mol Biol Rep.  37, 155-158.
2. Wang J.,Zou L., Huang S., et al. (2010) Genetics polymorphism of glutation-S-transferaze genes GSTM1and GSTT1 and risk coronary heart disease. Mutagenesis. 25:365-369.
3. Nafissi S., Saadat I., Saadat M. (2011) Genetics polymorphism of glutation-S-transferaze Z1 in Iranian population. Mol Biol Rep. 38:3391-3394.
4. Piacentini S., Polimanti R., Porreca F. (2011) GSTT1 and GSTM1 gene polymorphisms in European and African populations. Mol Biol Rep. 38:1225–1230.
5. Gupta V., Singh M., Amarapurkar D. et al. (2013) Association of GST null genotypes with anti-tuberculosis drug induced hepatotoxicity in Western Indian population. Ann Hepatol. 12(6):959-965.
6. Okada R, Ishizu Y, Endo R, Lezhava A, et al. (2010) Direct and rapid genotyping of glutathione-S-transferase M1 and T1 from human blood specimens using the SmartAmp2 method. Drug Metab Dispos.  Oct; 38(10):1636-1639.

Biography:

Tamar Buadze is PhD in biology. She is Senior Scientist in department of genetics, Ivane Javakhishvili Tbilisi State University. The field of her interest is the human genetics, exactly, medical genetics. She is principal investigator in grant projects, which concerns investigation of genetic parameters in different diseases, such as cardiomyopathy, tuberculosis and tumor - namely breast cancer. By her participation was determined the types of mutations and epigenetic variability - namely the degree of heterochromatinization, during the aging, atherosclerosis, cardiomyopathy, breast and lung cancers, in Georgian population. In some cases, the possibility of correction of altered genetic parameters by different agents. The results of the study are published in scientific journals.

Abstract:

Pulmonary Tuberculosis (PT) is classified as a disease with a hereditary predisposition. Genetic factors contribute to the outcome of primary PT infection, with an estimated heritability of more than 50%[1,2]. The genotype of an organism plays an important role in the development of PT diseases. Numerous studies have been performed to identify genetic factors responsible for variation in PT susceptibility[3]; however, none of the candidate genes was associated with susceptibility to active PT[4,5]. Therefore, as with all the pathologies related to this group, particular importance is attached to finding those markers that enable early detection of high risk groups of the disease in the population. Data on the variability of such informative and important functional parameters, which are associated with the epigenetic processes in PT, are practically absent.

The aim of our study was to evaluate genetic and epigenetic variation of the genome in patients with sensitive Pulmonary Tuberculosis (PT) before and after treatment, under the effect of peptide bioregulator–Ala-Glu-Asp-Gly.

In lymphocyte cultures from patients with sensitive primary PT were studied: facultative heterochromatin (sister chromatid exchanges - SCE) and mutation(chromosome aberrations).

We determined: There was an epigenetic alteration of functional parameters of the genome in PT before treatment. The level of heterochromatin decreased in the telomeric regions of chromosomes - A1,A2,B,C,D,F and G (in control it was high)  and increased in the middle regions of chromosomes - A1,B,C,E,F, and G (in control it was reduced); There was a high level of somatic recombination; Revealed an increase of the frequency of cells with chromosome aberrations. The bioregulator (Ala-Glu-Asp-Gly) could be used as an aid in the prevention and treatment of tuberculosis.

The results of our study - redistribution of heterochromatin from the telomeric to middle chromosome arms and increasing of chromosome aberrations make it possible to define a sensitive form of PT, and then monitor the results of treatment