Day 2 :
Keynote Forum
Vojin Rakić
Center for the Study of Bioethics-University of Belgrade, Serbia
Keynote: What is involuntary moral enhancement?
Biography:
Vojin Rakić is a Full Professor and is Director of the Center for the Study of Bioethics and Head of the European Division of the UNESCO Chair in Bioethics. He is also Chair of the Cambridge Working Group for Bioethics Education in Serbia. He is also Head of the Serbian Unit of the UNESCO Chair in Bioethics. He has a PhD in Political Science from Rutgers University in the United States (1998). He has graduated in Philosophy in Serbia and has MA degrees in European Studies from the Central European University in Prague and from the Department of Political Science of Rutgers University. He has worked as a Senior Research Fellow at the Center for Higher Education Policy Studies at the University of Twente in the Netherlands (1999-2001). Between 2001 and 2003, he was a U.N. Special Adviser to the Government of Serbia. Since 2003 he works as a university Professor in Belgrade. His publications include various books and edited collections, as well as numerous articles from the domain of (bio-)ethics and political philosophy.
Abstract:
During the previous years, voluntary moral bioenhancement (VMBE) has been contrasted to Compulsory Moral Bioenhancement (CMBE), promoted primarily by Persson and Savulescu. In this presentation a third possible type of MBE will be discussed: Genome editing for moral enhancement of the unborn that is neither voluntary nor compulsory, but involuntary. The focus of the presentation will therefore be on genome editing that is aimed at moral enhancement of human offspring. It will be argued that genome editing might have the potential to engineer human offspring in three domains: To be more empathetic, less violently aggressive and with a higher potential for complex moral reflection. Genome editing will be discussed in these three domains. It will be argued that a combination of VMBE and IMBE might be the best option humans have to enhance themselves morally.
Keynote Forum
Meena Upadhyaya
Cardiff University, UK
Keynote: Recent developments in neurofibromatosis type 1 and RASopathies: Novel therapeutic targets
Time : 11:00-12:00
Biography:
Professor Meena Upadhyaya OBE, is a distinguished professor in the Division of Cancer and Genetics, Cardiff university, UK. She obtained her PhD in Medical Genetics from Cardiff University and gained FRCPath from Royal College of Pathologists, London. She has made substantial contributions to the molecular understanding of a number of genetic conditions including neurofibromatosis type 1, facioscapulohumeral muscular dystrophy, Legius syndrome, Charcot Marie Tooth disease, Duchenne Muscular Dystrophy, Sotos syndrome, Hunters syndrome inter alia and also supervised numerous PhD, MD, MSc and undergraduate students. Prof. Upadhyaya has published well over 200 papers in peer reviewed journals and co-edited three books and sits on a number of Committees. She is also passionate about women’s equality in all spheres of life.
Abstract:
Neurofibromatosis type 1 (NF1) is a common autosomal dominantly inherited tumor predisposition syndrome affecting 1/3000-4000 individuals worldwide. Neurofibromin, the protein encoded by NF1 gene down-regulates Ras. The Ras/MAPK pathway plays an essential role in regulating the cell cycle and cellular growth, differentiation and senescence, all of which are critical to normal development. In NF1 patients, benign plexiform neurofibromas can transform into aggressive malignant tumors called Malignant Peripheral Nerve Sheath Tumors (MPNSTs), currently, there are no effective treatments for MPNSTs. The RASopathies are a clinically defined group of medical genetic syndromes caused by germline mutations in genes that encode components or regulators of the Ras/MAPK pathway. These disorders include neurofibromatosis type 1, Legius syndrome, Noonan syndrome, Noonan syndrome with multiple lentigines (LEOPARD), capillary arteriovenous malformation syndrome, Costello syndrome cardiofaciocutaneous syndrome and SYNGAP1 autism. Because of the common underlying Ras/MAPK pathway dysregulation, they have overlapping phenotypic features, including cancer, facial dysmorphia, neurocognitive impairment, pain and cardiovascular, musculoskeletal, gastrointestinal and cutaneous abnormalities. NF1 was the first Rasopathy syndrome reported in the RAS pathway. Several ongoing clinical trials exist for RASopathies including NF1 and effective treatments for certain clinical features are on horizon. NF1 also has great importance and significance in a number of sporadic cancers and functions as a central tumor suppressor gene in these cancers. With the recent advances in sequencing technologies, high-throughput drug discovery platforms, increasing availability of more sophisticated animal models and application of the state-of-art tumor imaging techniques, diagnosis and treatment of patients with RASopathies is improving.
- Immunogenetics | Thalassemia | Genetic Diseases | Human Genetics | Nutrigenomics | Human Evolutionary Genetics | Pharmacogenomics and Pharmacogenetics | Regenerative Medicine | Genetic Counseling | Neurogenetics | Epigenetics | Behavioural Genetics
Location: Andromeda | Radisson Blu Hotel, Abu Dhabi Yas Island
Chair
Mariam Fida
Arabian Gulf University, Bahrain
Session Introduction
Mohammed Chyad Hammoodi Al-Noaemi et al.
Al-Ghad International College for Applied Medical Sciences, KSA
Title: A family case report of tyrosinemia type-1 from Najran province of Saudi Arabia
Biography:
Mohammed Chyad Hammoodi Al-Noaemi has completed his Ph.D. from University of Newcastle upon-Tyne (UK) in Physiology. Then after, he was involved in teaching physiology in more than 30 medical and paramedical colleges in Iraq, Sudan, Jordan, and Saudi Arabia. Currently, he is a professor of physiology in Al-Ghad International College in Najran-KSA. He has published about 50 papers in reputed journals.
Abstract:
Tyrosinemia-1 is a very rare and severe inborn metabolic disorder affecting about 1 in 100,00 to 120,000 births worldwide. The pathophysiology of the disease is explained by the subsequent accumulation of tyrosine and its toxic metabolite in blood and tissues causing dysfunction of these organs, affecting mainly the liver and the kidney. The patient may develop acute liver failure in early infancy. The untreated survivors of the acute failure show liver cirrhosis, renal tubulopathy, rickets and hepatocellular carcinoma. The diagnosis of the disease depends on the clinical features and biochemical tests as detecting an increase in tyrosine and its metabolites in blood and urine. The main aim of this study was first; to report for the first time a family case of tyrosinemia in Najran city, the southern province of Saudi Arabia (KSA). Secondly; to increase the social and medical community awareness of the disease as consanguineous marriages are very common in this area.
Biography:
Budoor Alqarni is an Application Scientist at MGI. Budoor Alqarni has completed her PhD from the University of New South Wales, Australia in the field of Molecular biology. She did her Master of Science in Medicine in Infectious disease and Immunity from the University of Sydney. Budoor Alqarni has extended working experience Clinical diagnostic, Scientific research and Technical Support.
Abstract:
Zeinab Deris Zayeri
Ahvaz Jundishapur University of Medical Sciences, Iran
Title: A novel infram deletion in MSH6 gene in glioma: Conversation on MSH6 mutations in brain tumors
Biography:
Zeinab Deris Zayeri has completed her Msc in Human Genetic from Genetic department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. She is the Head of Clinical Labratory in Ahvaz. She has published more than 20 papers in reputed journals and has been serving as an Editorial Board Member of Cancer Research Journal.
Abstract:
Background & Aim: Histological and molecular information and biopsy help in the diagnosis of the type and grade of tumors and increase the value of estimation of the biological behavior of tumors. In this study, we aim on a consanguineous Iranian family with high prevalence of brain tumors in their pedigree and reviewed the literature on MSH6 mutations in brain tumors and the treatment responses focused on gliomas. Method: We chose a family with a high prevalence of brain tumor in their pedigree. We studied the proband's neuroimaging and brain proton Magnetic Resonance Spectroscopy (MRS), Magnetic Resonance Imaging (MRI), biopsy result and whole genome sequencing. Result: The neuroimaging and brain proton MRS reported a lesion in the right frontoparietal. The MRI revealed a large enhancible heterogenous mass in the right temporoâ€frontoâ€parietoâ€occipital lobes with involvement of corpus callosum which was suggestive of glioma. The patient revealed a homozygous pattern for a novel 9 baseâ€pare deletion at the 912-914 codon on exon 4 of the MSH6 gene. Discussion: We discuss several studies on MSH6 mutations in brain tumors and we discuss treatment responses in MSH6 mutations and the studies conducted to sensitize chemotherapy and radiotherapy resistance brain tumors to face this subject efficiently. Conclusion: Patients should be evaluated for MMR mutation before chemo and radiotherapy, and it is valuable to followâ€up these mutations during the treatment too. In Temozolomide (TMZ)â€resitance cases, it is suggested to use complementary strategies such as using HDAC is and a combination of a STAT3 Inhibitor and an mTOR inhibitor, BER inhibition mechanism and PARPâ€1 inhibitor. The highlights of this study are central nervous system tumors are rare and they are responsible for approximately 20-30% of cancer morbidity in children and youngsters, Mismatch Repair (MMR) mutations and mutations in the DNAâ€repair system are probably related to tumor progression and chemo and radiotherapy resistance, germline mutations of MSH6 increase the susceptibility to gliomas and somatic mutations cause temozolomide (TMZ)â€resistance manner, inhibition of NAD+ biosynthesis increases the expression of MGMT and this can support the deficiency of MMR proteins. Making a connection between the genetic profiles and the evolved pathways and therapeutic approaches enhance our vision in estimating the results beyond treatment.
Fawz Al Harthi
King Saud Medical City, Saudi Arabia
Title: Attitudes toward preimplantation genetic diagnosis vs. pre-natal diagnosis in Saudi Arabian couples with children with genetic disorders
Biography:
Fawz Al Harthi has completed her Bachelor of Science in Biomedical Science from the University of Kingston in London, England and her Masters of Genetic Counseling at Al-Faisal University in Riyadh, Saudi Arabia. She is currently a Clinician in the Pediatric Genetic Clinic at King Saud Medical City in Riyadh. She has also worked at the Medical Genetic Clinic and the Saudi Diagnostic Laboratory at King Faisal Specialist Hospital Research Center in Riyadh.
Abstract:
Background & Aim: Couples who are at risk for having an infant with a serious genetic disorder can benefit from Pre-implantation Genetic Diagnosis (PGD), but many couples still opt for the more risky Pre-Natal Diagnosis (PND). Although couples make this decision together, the male and the female in the couple may have different attitudes toward choosing PGD vs. PND. The aim of this study was to determine if men and women in the same couple with at least one child with a genetic disorder will have significantly different attitudes toward choosing PGD vs. PND. Method: In this cross-sectional clinical study, couples attending the King Faisal Hospital, Genetic Counseling Clinic (KFH-GCC), in Riyadh, Saudi Arabia were asked to complete an anonymous survey about their attitudes towards PGD vs. PND. The responses were compared between men and women in the couples. Result: During May 2017, 38 couples provided complete surveys; 58% had one child born with a genetic disorder and the remaining had more than one child born with a genetic disorder. Over half (50%) of both men and women in the couples had Bachelors degrees or higher levels of education and the most common primary reason for visiting the clinic was having a child or children with a genetic disorder already (men=84%, women=82%). In terms of preference for PGD vs. PND, there were no significant differences in aggregate between men and women (p>0.05). Over half the couples agreed (were concordant) on all statements about PGD vs. PND. Among members of couples, discordance between preference for PND and PGD was similar, in that roughly equal numbers of discordant couples had women preferring PGD vs. men preferring PGD compared to PND. Conclusion: This study showed that members of couples who are patients of the KFH-GCC with a child with at least one genetic disorder were generally in agreement about their preference for PGD vs. PND. Further, men and women did not have significantly different attitudes toward choosing PGD vs. PND and among discordant couples, there was no preference among women for PGD vs. PND. Studies like this are important to help clinicians understand intra-couple dynamics in genetic counseling.
Manisha Mishra et al.
All India Institute of Medical Sciences, India
Title: Association of MMP2 gene polymorphisms (-735C/T and -1306C/T) in preeclamptic patients in Indian population
Biography:
Manisha Mishra had completed Bachelor of Dental Surgery and MSc Anatomy from All India Institute of Medical Sciences, New Delhi, India. She is currently a Senior Reseach Fellow at All India Institute of Medical Sciences, India.
Abstract:
Introduction & Aim: Imbalanced Matrix Metalloproteinase (MMP) expression, including MMP2, has been demonstrated in preeclampsia. However, little is known about the effect of MMP2 gene polymorphisms on hypertensive disorders of pregnancy. Therefore, we examined matrix metalloproteinase (MMP2) gene polymorphisms (g.-735C/T and -1306 C/T) and their association with Preeclampsia (PE) and measured the levels of MMP2 serum concentrations in PE Patients. Material & Methods: 30 preeclamptic and 30 healthy pregnant women (control group) were enrolled from Department of Obstetrics and Gynecology, AIIMS, New Delhi after getting approval from Institute Ethical Committee. Genomic DNA was extracted from blood and amplified by PCR. MMP2 gene polymorphisms of -735C/T and -1306 C/T were detected by Restriction Fragment Length Polymorphism (RFLP). The levels of MMP2 in sera were measured by ELISA. Results: The maternal serum MMP2 levels was found to be more in PE patients as compared to control group (p=0.03). The increased frequency of CT genotype for MMP2 (-735C/T) Single Nucleotide Polymorphism was seen in PE patients as compared to control group whereas the MMP2-1306C/T (rs243865) didn’t show any change in patients as well as controls. However the difference in genotype frequency in both polymorphisms was not statistically significant. Conclusion: More no of sample size is required to understand the relevance of MMP2 and its genetic polymorphisms in the pathophysiology of hypertensive disorders of pregnancy like preeclampsia and IUGR.
Nada Abuarab
King Saud Bin Abdul-Aziz University for Health Sciences, Saudi Arabia
Title: High glucose-induced ROS activates TRPM2 to regulate organelle zinc homeostasis and mitochondrial fragmentation
Biography:
Nada Abuarab has completed her MSc in Bioscience and PhD in Philosophy from School of Biomedical Sciences, University of Leeds, UK. She is currently working as an Assistant Professor in Basic Science Department, King Saud Bin Abdul-Aziz University for Health Sciences, Saudi Arabia. She has also obtained a second Master’s degree in Medical Education form College of Medicine, King Saud Bin Abdul-Aziz University for Health Sciences.
Abstract:
Mitochondria plays a central role in oxidative stress induced cell death. By increasing the production of reactive oxygen species, such as H2O2, oxidative stress causes mitochondrial fragmentation and apoptosis. Mechanisms by which oxidative stress leads to apoptosis, however, are not fully understood. Here we hypothesised that Transient Receptor Potential Melastatin 2 (TRPM2) channels play a role in mitochondrial fragmentation. The rationale behind this is the previous evidence that TRPM2 channels are activated by H2O2 and conduct ions (Ca2+ and Zn2+) that affect mitochondrial health and cell survival. To test our hypothesis we have used live-cell imaging, immunostaining, biochemical techniques and cell death assays. Exposure of Human Umbilical Vein Endothelial Cells (HUVECs) to H2O2 led to an increase in Zn2+ levels in the mitochondria and a reduction in lysosomes. This redistribution was accompanied by an extensive fragmentation of mitochondria and an increase in cell death. Silencing of TRPM2 channel prevented intracellular Zn2+ redistribution, mitochondrial fragmentation and cell death. TRPM2 activation increased recruitment of Dynamin-Related protein 1 (Drp1) to mitochondria, thereby increasing mitochondrial fission. Moreover, the data indicated that TRPM2 is expressed in lysosomes presumably to mediate Zn2+ release. Endothelial cells derived from TRPM2 knock-out mice were resistant to oxidative stress-induced mitochondrial fragmentation. In conclusion, our data revealed a novel mechanism where H2O2 activation of TRPM2 causes a redistribution of Zn2+ from lysosomes to mitochondria, resulting in mitochondrial fragmentation and endothelial cell death. Since mitochondrial fragmentation is associated with several age-related chronic illnesses including neuronal (Alzheimer’s, Parkinson’s), cardiovascular (atherosclerosis, myocardial infarction) and metabolic/inflammatory (diabetes) disorders, our results reveal TRPM2 channel as potional therapeutic intervention of age-related illnesses.
Mavlyanova Shakhnoza Zakirovna et al.
Ministry of Health of the Republic of Uzbekistan, Uzbekistan
Title: The role of the polymorphic variant of the IIe 105Val genes of the GSTP1 in the mechanism of the development of allergic skin diseases in Uzbekistan
Biography:
Mavlyanova Shakhnoza Zakirovna received Doctor of Medical Sciences degree at the Higher Attestation Commission under the Cabinet of Ministers of the Republic of Uzbekistan. She is the Head of the Scientific Department of Dermatology of the Republican Specialized Scientific and Practical Medical Center of Dermatovenereology and Cosmetology, Ministry of Health of the Republic of Uzbekistan. She is a Member of the Association of Dermatovenereologists and Cosmetologists of the Republic of Uzbekistan and the European Academy of Dermatovenerologists. She has published over 300 articles in well-known journals, has 7 patents for inventions, 5 monographs and is also a Member of the Editorial Board of the Journal of Dermatovenereology and Cosmetology of Uzbekistan.
Abstract:
Aim: It is the study of polymorphism of genes of enzymes of biotransformation of xenobiotics in patients with allergic skin diseases. Material & Methods: Patients with allergic dermatoses (AlD), DNA samples of patients and healthy donors, glutathione-transferase GSTM1 (1p13.3), GSTT1 (22q11.2) and IIe 105Val genes of the GSTP1 gene were the object and subject of the study. The study included 88 patients with AlD age ranging from 5 to 67 years. Of these, 41 are women, 50 are men. The diagnosis in all patients is confirmed by the results of the clinical examination and laboratory tests. Results: Among patients with allergic dermatoses, individuals with combined functionally inferior genotypes GSTM10/0+GSTT10/0 were more common than in the group of healthy individuals (6.8% vs. 4.1%, respectively, χ2=0.5; P=0.4; OR=1.7, 95% CI 0.405-6.979). The obtained data indicate that in individuals with zero genotypes of genes of xenobiotic enzymes GSTM1 and GSTT1 there is a tendency to the risk of allergic dermatosis development. Whereas, with the combined variants of zero and functional genotypes of polymorphism of the GSTM1 and GSTT1 genes, there were no statistically significant differences between the groups studied (p>0.05). While the frequency distribution of the occurrence of alleles and genotypes of GSTP1 in the group of patients with allergodermatosis, in comparison with the control group, significant differences were found. The functionally unfavorable allele G of the GSTP1 gene was 3.4 times statistically significantly more prevalent in the studied chromosomes of allergic dermatoses than in the population sample (χ2=10.8; P<0.05; OR=3.4; 95% CI 1.6-7.4). The associations of functionally unfavorable A/G genotypes were identified (χ2=6.9, P<0.05, OR=2.6, 95% CI 1.264-5.382) and G/G (χ2=8.0; P<0.05; OR=11.2; 95% CI 1.421-88.43) with the development of allergic dermatoses. Conclusion: Genes of glutathione transferase, polymorphism IIe 105 Val of the GSTP1 gene is the most significant marker of an increased risk of allergic skin diseases in Uzbekistan.
Nigora Mavlyanova et al.
Ministry of Health of the Republic of Uzbekistan, Uzbekistan
Title: To indicators of the detection of alleles and genotypes of polymorphism (rs1695) IIe 105 Val FGB gene in pregnant women in Uzbekistan
Biography:
Nigora Mavlyanova is the Scientific Leader of the Youth Applied Grant from the Republican Specialized Scientific and Practical Medical Center of Obstetrics and Gynecology, Ministry of Health of the Republic of Uzbekistan. She is a Member of the Association of Obstetricians and Gynecologists of the Republic of Uzbekistan. She has published over 20 articles in famous magazines.
Abstract:
Background & Aim: The search for genetic markers associated with the development of placental insufficiency is the most important task for understanding the pathogenesis, treatment and prevention of the disease. The purpose of our research was to determine the frequency of polymorphisms of hemostasis and fibrinolysis genes: FGB, in pregnant women, and to identify the distribution patterns of these polymorphisms in the clinical course of fetoplacental insufficiency (FPN). Method: The object and subject of the study were pregnant women, patient DNA samples and the fibrinolysis gene (rs1695) IIe 105 Val of the FGB gene. The study included 50 pregnant women aged from 20 to 45 years who were observed at the base of the clinic of the National Scientific Practical Medical Center for obstetrics and gynecology Ministry of Health of the Republic of Uzbekistan. Result: The results of clinical, instrumental and functional studies among 50 pregnant women showed a high detectability of FPN in 40, which accounted for 80% of cases. Molecular genetic analysis of distribution frequencies of alleles and genotypes of IIe 105 Val polymorphism of the FGB fibrinolysis gene among 80 DNA samples in 40 pregnant women with FPN in 87.5% of cases revealed the presence of a normal allele A and in 12.5% of cases -the allele G, respectively. (Χ2=0.1; P=0.8; OR=1.2; 95% CI 0.306-4.983). Whereas, in the control group in 10 pregnant women without FPN, the frequency of occurrence of the normal allele A of the FGB gene was 85%, whereas the mutant A IIe 105 Val allele of the FGB gene was 15%, respectively. Indicators of the frequency distribution of genotypes by RCS of IIe 105 Val polymorphism of the FGB gene in the main group of pregnant women with FPN showed that the observed frequency of A/A genotypes was found in 75.0%, heterozygous A/G genotypes-25.0% and homozygous-G/G-0%, respectively, whereas the expected frequency of the genotypes of group A/A and heterozygous A/G were 76.6% and 21.8%, respectively and G/G-in 1.56% of cases. For the IIe 105Val FGB gene in the group of pregnant women with PSP, the empirical (Hobs) distribution of genotypes corresponds to the theoretically expected (Hexp) in PSC (p>0.05). Conclusion: Analysis of the obtained results shows that the distribution of all genotypes of the A/G polymorphism of the FGB gene in the group of pregnant women with FPN and the control of healthy individuals corresponds to RCS. The study of the genetic structure of this marker revealed a tendency to increase the expected mutant in the main group of pregnant women with NEF in relation to the group without NEF (10% and 2.25%, respectively). The results require further study of this gene in pregnant women.