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Open Access

Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015)

Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015
BMC Genomics201617(Suppl 6):487

https://doi.org/10.1186/s12864-016-2858-0

Published: 20 July 2016

Table of contents

O1 Regulation of genes by telomere length over long distances

Jerry W. Shay

O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy

Noriko Homma, Ruyun Zhou, Muhammad Imran Naseer, Adeel G. Chaudhary, Mohammed Al-Qahtani, Nobutaka Hirokawa

O3 Integration of metagenomics and metabolomics in gut microbiome research

Maryam Goudarzi, Albert J. Fornace Jr.

O4 A unique integrated system to discern pathogenesis of central nervous system tumors

Saleh Baeesa, Deema Hussain, Mohammed Bangash, Fahad Alghamdi, Hans-Juergen Schulten, Angel Carracedo, Ishaq Khan, Hanadi Qashqari, Nawal Madkhali, Mohamad Saka, Kulvinder S. Saini, Awatif Jamal, Jaudah Al-Maghrabi, Adel Abuzenadah, Adeel Chaudhary, Mohammed Al Qahtani, Ghazi Damanhouri

O5 RPL27A is a target of miR-595 and deficiency contributes to ribosomal dysgenesis

Heba Alkhatabi

O6 Next generation DNA sequencing panels for haemostatic and platelet disorders and for Fanconi anaemia in routine diagnostic service

Anne Goodeve, Laura Crookes, Nikolas Niksic, Nicholas Beauchamp

O7 Targeted sequencing panels and their utilization in personalized medicine

Adel M. Abuzenadah

O8 International biobanking in the era of precision medicine

Jim Vaught

O9 Biobank and biodata for clinical and forensic applications

Bruce Budowle, Mourad Assidi, Abdelbaset Buhmeida

O10 Tissue microarray technique: a powerful adjunct tool for molecular profiling of solid tumors

Jaudah Al-Maghrabi

O11 The CEGMR biobanking unit: achievements, challenges and future plans

Abdelbaset Buhmeida, Mourad Assidi, Leena Merdad

O12 Phylomedicine of tumors

Sudhir Kumar, Sayaka Miura, Karen Gomez

O13 Clinical implementation of pharmacogenomics for colorectal cancer treatment

Angel Carracedo, Mahmood Rasool

O14 From association to causality: translation of GWAS findings for genomic medicine

Ahmed Rebai

O15 E-GRASP: an interactive database and web application for efficient analysis of disease-associated genetic information

Sajjad Karim, Hend F Nour Eldin, Heba Abusamra, Elham M Alhathli, Nada Salem, Mohammed H Al-Qahtani, Sudhir Kumar

O16 The supercomputer facility “AZIZ” at KAU: utility and future prospects

Hossam Faheem

O17 New research into the causes of male infertility

Ashok Agarwa

O18 The Klinefelter syndrome: recent progress in pathophysiology and management

Eberhard Nieschlag, Joachim Wistuba, Oliver S. Damm, Mohd A. Beg, Taha A. Abdel-Meguid, Hisham A. Mosli, Osama S. Bajouh, Adel M. Abuzenadah, Mohammed H. Al-Qahtani

O19 A new look to reproductive medicine in the era of genomics

Serdar Coskun

P1 Wnt signalling receptors expression in Saudi breast cancer patients

Muhammad Abu-Elmagd, Abdelbaset Buhmeida, Ashraf Dallol, Jaudah Al-Maghrabi, Sahar Hakamy, Wejdan Al-Qahtani, Asia Al-Harbi, Shireen Hussain, Mourad Assidi, Mohammed Al-Qahtani, Adel Abuzenadah

P2 Analysis of oxidative stress interactome during spermatogenesis: a systems biology approach to reproduction

Burak Ozkosem, Rick DuBois

P3 Interleukin-18 gene variants are strongly associated with idiopathic recurrent pregnancy loss.

Safia S Messaoudi, Maryam T Dandana, Touhami Mahjoub, Wassim Y Almawi

P4 Effect of environmental factors on gene-gene and gene-environment reactions: model and theoretical study applied to environmental interventions using genotype

S. Abdalla, M. Nabil Al-Aama

P5 Genomics and transcriptomic analysis of imatinib resistance in gastrointestinal stromal tumor

Asmaa Elzawahry, Tsuyoshi Takahashi, Sachiyo Mimaki, Eisaku Furukawa, Rie Nakatsuka, Isao Kurosaka, Takahiko Nishigaki, Hiromi Nakamura, Satoshi Serada, Tetsuji Naka, Seiichi Hirota, Tatsuhiro Shibata, Katsuya Tsuchihara, Toshirou Nishida, Mamoru Kato

P6 In-Silico analysis of putative HCV epitopes against Pakistani human leukocyte antigen background: an approach towards development of future vaccines for Pakistani population

Sajid Mehmood, Naeem Mahmood Ashraf, Awais Asif, Muhammad Bilal, Malik Siddique Mehmood, Aadil Hussain

P7 Inhibition of AChE and BuChE with the natural compounds of Bacopa monerri for the treatment of Alzheimer’s disease: a bioinformatics approach

Qazi Mohammad Sajid Jamal, Mughees Uddin Siddiqui, Mohammad A. Alzohairy, Mohammad A. Al Karaawi

P8 Her2 expression in urothelial cell carcinoma of the bladder in Saudi Arabia

Taoufik Nedjadi, Jaudah Al-Maghrabi, Mourad Assidi, Heba Al-Khattabi, Adel Al-Ammari, Ahmed Al-Sayyad, Abdelbaset Buhmeida, Mohammed Al-Qahtani

P9 Association of angiotensinogen single nucleotide polymorphisms with Preeclampsia in patients from North Africa

Hédia Zitouni, Nozha Raguema, Marwa Ben Ali, Wided Malah, Raja Lfalah, Wassim Almawi, Touhami Mahjoub

P10 Systems biology analysis reveals relations between normal skin, benign nevi and malignant melanoma

Mohammed Elanbari, Andrey Ptitsyn

P11 The apoptotic effect of thymoquinone in Jurkat cells

Sana Mahjoub, Rabeb El Ghali, Bechir Achour, Nidhal Ben Amor, Mourad Assidi, Brahim N'siri, Hamid Morjani

P12 Sonic hedgehog contributes in bladder cancer invasion in Saudi Arabia

Taoufik Nedjadi, Adel Al-Ammari, Ahmed Al-Sayyad, Nada Salem, Esam Azhar, Jaudah Al-Maghrabi

P13 Association of Interleukin 18 gene promoter polymorphisms - 607A/C and -137 G/C with colorectal cancer onset in a sample of Tunisian population

Vera Chayeb, Maryam Dendena, Hedia Zitouni, Khedija Zouari-Limayem, Touhami Mahjoub

P14 Pathological expression of interleukin-6, -11, leukemia inhibitory factor and their receptors in tubal gestation with and without tubal cytomegalovirus infection

Bassem Refaat, Ahmed M Ashshi, Sarah A Batwa

P15 Phenotypic and genetic profiling of avian pathogenic and human diarrhegenic Escherichia coli in Egypt

Hazem Ramadan, Amal Awad, Ahmed Ateya

P16 Cancer-targeting dual gene virotherapy as a promising therapeutic strategy for treatment of hepatocellular carcinoma

Adel Galal Ahmed El-Shemi, Ahmad Ashshi, Mohammed Basalamah, Youjin Na, Chae-Ok YUN

P17 Cancer dual gene therapy with oncolytic adenoviruses expressing TRAIL and IL-12 transgenes markedly eradicated human hepatocellular carcinoma both in vitro and in vivo

Adel Galal Ahmed El-Shemi, Ahmad Ashshi, Mohammed Basalamah, Youjin Na, Chae-Ok Yun

P18 Therapy with paricalcitol attenuates tumor growth and augments tumoricidal and anti-oncogenic effects of 5-fluorouracil on animal model of colon cancer

Adel Galal El-Shemi, Bassem Refaat, Osama Kensara, Amr Abdelfattah

P19 The effects of Rubus idaeus extract on normal human lymphocytes and cancer cell line

Batol Imran Dheeb, Mohammed M. F. Al-Halbosiy, Rghad Kadhim Al lihabi, Basim Mohammed Khashman

P20 Etanercept, a TNF-alpha inhibitor, alleviates mechanical hypersensitivity and spontaneous pain in a rat model of chemotherapy-induced neuropathic pain

Djouhri, Laiche, Chaudhary Adeel, Nedjadi, Taoufik

P21 Sleeping beauty mutagenesis system identified genes and neuronal transcription factor network involved in pediatric solid tumour (medulloblastoma)

Hani Al-Afghani, Maria Łastowska, Haya H Al-Balool, Harsh Sheth, Emma Mercer, Jonathan M Coxhead, Chris PF Redfern, Heiko Peters, Alastair D Burt, Mauro Santibanez-Koref, Chris M Bacon, Louis Chesler, Alistair G Rust, David J Adams, Daniel Williamson, Steven C Clifford, Michael S Jackson

P22 Involvement of interleukin-1 in vitiligo pathogenesis

Mala Singh, Mohmmad Shoab Mansuri, Shahnawaz D. Jadeja, Hima Patel, Yogesh S. Marfatia, Rasheedunnisa Begum

P23 Cytogenetics abnormalities in 12,884 referred population for chromosomal analysis and the role of FISH in refining the diagnosis (cytogenetic experience 2004-2013)

Amal M Mohamed, Alaa K Kamel, Nivin A Helmy, Sayda A Hammad, Hesham F Kayed, Marwa I Shehab, Assad El Gerzawy, Maha M. Ead, Ola M Ead, Mona Mekkawy, Innas Mazen, Mona El-Ruby

P24 Analysis of binding properties of angiotensin-converting enzyme 2 through in silico method

S. M. A. Shahid, Qazi Mohammad Sajid Jamal, J. M. Arif, Mohtashim Lohani

P25 Relationship of genetics markers cis and trans to the β-S globin gene with fetal hemoglobin expression in Tunisian sickle cell patients

Moumni Imen, Chaouch Leila, Ouragini Houyem, Douzi Kais, Chaouachi Dorra Mellouli Fethi, Bejaoui Mohamed, Abbes Salem

P26 Analysis of estrogen receptor alpha gene polymorphisms in breast cancer: link to genetic predisposition in Sudanese women

Areeg Faggad, Amanuel T Gebreslasie, Hani Y Zaki, Badreldin E Abdalla

P27 KCNQI gene polymorphism and its association with CVD and T2DM in the Saudi population

Maha S AlShammari, Rhaya Al-Ali, Nader Al-Balawi , Mansour Al-Enazi, Ali Al-Muraikhi, Fadi Busaleh, Ali Al-Sahwan, Francis Borgio, Abdulazeez Sayyed, Amein Al-Ali, Sadananda Acharya

P28 Clinical, neuroimaging and cytogenetic study of a patient with microcephaly capillary malformation syndrome

Maha S. Zaki, Hala T. El-Bassyouni, Marwa I. Shehab

P29 Altered expression of CD200R1 on dendritic cells of patients with inflammatory bowel diseases: in silico investigations and clinical evaluations

Mohammed F. Elshal, Kaleemuddin M., Alia M. Aldahlawi, Omar Saadah,

J. Philip McCoy

P30 Development of real time PCR diagnostic protocol specific for the Saudi Arabian H1N1 viral strains

Adel E El-Tarras, Nabil S Awad, Abdulla A Alharthi, Mohamed M M Ibrahim

P31 Identification of novel genetic variations affecting Osteoarthritis patients

Haneen S Alsehli, Ashraf Dallol, Abdullah M Gari, Mohammed M Abbas, Roaa A Kadam, Mazen M. Gari, Mohmmed H Alkaff, Adel M Abuzenadah, Mamdooh A Gari

P32 An integrated database of GWAS SNVs and their evolutionary properties

Heba Abusamra, Sajjad Karim, Hend F Nour eldin, Elham M Alhathli, Nada Salem, Sudhir Kumar, Mohammed H Al-Qahtani

P33 Familial hypercholesterolemia in Saudi Arabia: prime time for a national registry and genetic analysis

Fatima A. Moradi, Omran M. Rashidi, Zuhier A. Awan

P34 Comparative genomics and network-based analyses of early hepatocellular carcinoma

Ibrahim Hamza Kaya, Olfat Al-Harazi, Dilek Colak

P35 A TALEN-based oncolytic viral vector approach to knock out ABCB1 gene mediated chemoresistance in cancer stem cells

Nabila A Alkousi, Takis Athanasopoulos

P36 Cartilage differentiation and gene expression of synovial fluid mesenchymal stem cells derived from osteoarthritis patients

Afnan O Bahmaid, Etimad A Alhwait, Mamdooh A Gari, Haneen S Alsehli, Mohammed M Abbas, Mohammed H Alkaf, Roaa Kadam, Ashraf Dallol, Gauthaman Kalamegam

P37 E-GRASP: Adding an evolutionary component to the genome-wide repository of associations (GRASP) resource

Hend F Nour Eldin, Sajjad Karim, Heba Abusamra, Elham Alhathli, Nada Salem, Mohammed H Al-Qahtani, Sudhir Kumar

P38 Screening of AGL gene mutation in Saudi family with glycogen storage disease Type III

Salma N Alsayed, Fawziah H Aljohani, Samaher M Habeeb, Rawan A Almashali, Sulman Basit, Samia M Ahmed

P39 High throughput proteomic data suggest modulation of cAMP dependent protein kinase A and mitochondrial function in infertile patients with varicocele

Rakesh Sharma, Ashok Agarwal, Damayanthi Durairajanayagam, Luna Samanta, Muhammad Abu-Elmagd, Adel M. Abuzenadah, Edmund S. Sabanegh, Mourad Assidi, Mohammed Al-Qahtani

P40 Significant protein profile alterations in men with primary and secondary infertility

Ashok Agarwal, Rakesh Sharma, Luna Samanta, Damayanthi Durairajanayagam, Mourad Assidi, Muhammad Abu-Elmagd, Mohammed Al-Qahtani, Adel M. Abuzenadah, Edmund S. Sabanegh

P41 Spermatozoa maturation in infertile patients involves compromised expression of heat shock proteins

Luna Samanta, Ashok Agarwal, Rakesh Sharma, Zhihong Cui, Mourad Assidi, Adel M. Abuzenadah, Muhammad Abu-Elmagd, Mohammed Al-Qahtani

P42 Array comparative genomic hybridization approach to search genomic answers for spontaneous recurrent abortion in Saudi Arabia

Alaa A Alboogmi, Nuha A Alansari, Maha M Al-Quaiti, Fai T Ashgan, Afnan Bandah, Hasan S Jamal, Abdullraheem Rozi, Zeenat Mirza, Adel M Abuzenadah, Sajjad Karim, Mohammed H Al-Qahtani

P43 Global gene expression profiling of Saudi kidney cancer patients

Sajjad Karim, Hans-Juergen Schulten, Ahmad J Al Sayyad, Hasan MA Farsi, Jaudah A Al-Maghrabi, Zeenat Mirza, Reem Alotibi, Alaa Al-Ahmadi, Nuha A Alansari, Alaa A Albogmi, Maha M Al-Quaiti, Fai T Ashgan, Afnan Bandah, Mohammed H Al-Qahtani

P44 Downregulated StAR gene and male reproductive dysfunction caused by nifedipine and ethosuximide

Rasha A Ebiya, Samia M Darwish, Metwally M. Montaser

P45 Clustering based gene expression feature selection method: A computational approach to enrich the classifier efficiency of differentially expressed genes

Heba Abusamra, Vladimir B. Bajic

P46 Prognostic significance of Osteopontin expression profile in colorectal carcinoma

Jaudah Al-Maghrabi, Wafaey Gomaa, Mehenaz Hanbazazh, Mahmoud Al-Ahwal, Asia Al-Harbi, Wejdan Al-Qahtani, Saher Hakamy, Ghali Baba, Abdelbaset Buhmeida, Mohammed Al-Qahtani

P47 High Glypican-3 expression pattern predicts longer disease-specific survival in colorectal carcinoma

Jaudah Al-Maghrabi, Abdullah Al-Harbi, Mahmoud Al-Ahwal, Asia Al-Harbi, Wejdan Al-Qahtani, Sahar Hakamy, Ghalia Baba, Abdelbaset Buhmeida, Mohammed Al-Qahtani

P48 An evolutionary re-assessment of GWAS single nucleotide variants implicated in the Cholesterol traits

Elham M Alhathli, Sajjad Karim, Nada Salem, Hend Nour Eldin, Heba Abusamra, Sudhir Kumar, Mohammed H Al-Qahtani

P49 Derivation and characterization of human Wharton’s jelly stem cells (hWJSCs) in vitro for future therapeutic applications

Aisha A Alyamani, Gauthaman Kalamegam, Etimad A Alhwait, Mamdooh A Gari, Mohammed M Abbas, Mohammed H Alkaf, Haneen S Alsehli, Roaa A Kadam, Mohammed Al-Qahtani

P50 Attitudes of healthcare students toward biomedical research in the post-genomic era

Rawan Gadi, Abdelbaset Buhmeida, Mourad Assidi , Adeel Chaudhary, Leena Merdad

P51 Evaluation of the immunomodulatory effects of thymoquinone on human bone marrow mesenchymal stem cells (BM-MSCs) from osteoarthritic patients

Saadiah M Alfakeeh, Etimad A Alhwait, Mamdooh A Gari, Mohammed M Abbas, Mohammed H Alkaf, Haneen S Alsehli, Roaa Kadam, Gauthaman Kalamegam

P52 Implication of IL-10 and IL-28 polymorphism with successful anti-HCV therapy and viral clearance

Rubi Ghazala, Shilu Mathew, M.Haroon Hamed, Mourad Assidi, Mohammed Al-Qahtani, Ishtiaq Qadri

P53 Selection of flavonoids against obesity protein (FTO) using in silico and in vitro approaches

Shilu Mathew, Lobna Mira, Manal Shaabad, Shireen Hussain, Mourad Assidi, Muhammad Abu-Elmagd, Mohammed Al-Qahtani

P54 Computational selection and in vitro validation of flavonoids as new antidepressant agents

Shilu Mathew, Manal Shaabad, Lobna Mira, Shireen Hussain, Mourad Assidi, Muhammad Abu-Elmagd, Mohammed Al-Qahtani

P55 In Silico prediction and prioritization of aging candidate genes associated with

progressive telomere shortening

Ahmed Rebai, Mourad Assidi, Abdelbaset Buhmeida, Muhammad Abu-Elmagd, Ashraf Dallol, Jerry W Shay

P56 Identification of new cancer testis antigen genes in diverse types of malignant human tumour cells

Mikhlid H Almutairi

P57 More comprehensive forensic genetic marker analyses for accurate human remains identification using massively parallel sequencing (MPS)

Angie Ambers, Jennifer Churchill, Jonathan King, Monika Stoljarova, Harrell Gill-King, Mourad Assidi, Muhammad Abu-Elmagd, Abdelbaset Buhmeida, Muhammad Al-Qatani, Bruce Budowle

P58 Flow cytometry approach towards treatment men infertility in Saudi Arabia

Muhammad Abu-Elmagd, Farid Ahmed, Ashraf Dallol, Mourad Assidi, Taha Abo Almagd, Sahar Hakamy, Ashok Agarwal, Muhammad Al-Qahtani, Adel Abuzenadah

P59 Tissue microarray based validation of CyclinD1 expression in renal cell carcinoma of Saudi kidney patients

Sajjad Karim, Hans-Juergen Schulten, Ahmad J Al Sayyad, Hasan MA Farsi, Jaudah A Al-Maghrabi, Abdelbaset Buhmaida, Zeenat Mirza, Reem Alotibi, Alaa Al-Ahmadi, Nuha A Alansari, Alaa A Albogmi, Maha M Al-Quaiti, Fai T Ashgan, Afnan Bandah, Mohammed H Al-Qahtani

P60 Assessment of gold nanoparticles in molecular diagnostics and DNA damage studies

Rukhsana Satar, Mahmood Rasool, Waseem Ahmad, Nazia Nazam, Mohamad I Lone, Muhammad I Naseer, Mohammad S Jamal, Syed K Zaidi, Peter N Pushparaj, Mohammad A Jafri, Shakeel A Ansari, Mohammed H Alqahtani

P61 Surfing the biospecimen management and processing workflow at CEGMR Biobank

Hanan Bashier, Abrar Al Qahtani, Shilu Mathew, Amal M. Nour, Heba Alkhatabi, Adel M. Abu Zenadah, Abdelbaset Buhmeida, Mourad Assidi, Muhammed Al Qahtani

P62 Autism Spectrum Disorder: knowledge, attitude and awareness in Jeddah, Kingdom of Saudi Arabia

Muhammad Faheem, Shilu Mathew, Shiny Mathew, Peter Natesan Pushparaj, Mohammad H. Al-Qahtani

P63 Simultaneous genetic screening of the coagulation pathway genes using the Thromboscan targeted sequencing panel

Hani A. Alhadrami, Ashraf Dallol, Adel Abuzenadah

P64 Genome wide array comparative genomic hybridization analysis in patients with syndromic congenital heart defects

Ibtessam R. Hussein, Adeel G. Chaudhary, Rima S Bader, Randa Bassiouni, Maha Alquaiti, Fai Ashgan, Hans Schulten, Mohamed Nabil Alama, Mohammad H. Al Qahtani

P65 Toxocogenetic evaluation of 1, 2-Dichloroethane in bone marrow, blood and cells of immune system using conventional, molecular and flowcytometric approaches

Mohammad I Lone, Nazia Nizam, Waseem Ahmad, Mohammad A Jafri, Mahmood Rasool, Shakeel A Ansari, Muhammed H Al-Qahtani

P66 Molecular cytogenetic diagnosis of sexual development disorders in newborn: A case of ambiguous genitalia

Eradah Alshihri, Muhammad Abu-Elmagd, Lina Alharbi, Mourad Assidi, Mohammed Al-Qahtani

P67 Identification of disease specific gene expression clusters and pathways in hepatocellular carcinoma using In Silico methodologies

Shilu Mathew, Peter Pushparaj Natesan, Muhammed Al Qahtani

P68 Human Wharton’s Jelly stem cell conditioned medium inhibits primary ovarian cancer cells in vitro: Identification of probable targets and mechanisms using systems biology

Gauthaman Kalamegam, Peter Natesan Pushparaj, Fazal Khan, Roaa Kadam, Farid Ahmed, Mourad Assidi, Khalid Hussain Wali Sait, Nisreen Anfinan, Mohammed Al Qahtani

P69 Mutation spectrum of ASPM (Abnormal Spindle-like, Microcephaly-associated) gene in Saudi Arabian population

Muhammad I Naseer, Adeel G Chaudhary, Mohammad S Jamal, Shilu Mathew, Lobna S Mira, Peter N Pushparaj, Shakeel A Ansari, Mahmood Rasool, Mohammed H AlQahtani

P70 Identification and characterization of novel genes and mutations of primary microcephaly in Saudi Arabian population

Muhammad I Naseer, Adeel G Chaudhary, Shilu Mathew, Lobna S Mira, Mohammad S Jamal, Sameera Sogaty, Randa I Bassiouni, Mahmood Rasool, Mohammed H AlQahtani

P71 Molecular genetic analysis of hereditary nonpolyposis colorectal cancer (Lynch Syndrome) in Saudi Arabian population

Mahmood Rasool, Shakeel A Ansari, Mohammad S Jamal, Peter N Pushparaj, Abdulrahman MS Sibiani, Waseem Ahmad, Abdelbaset Buhmeida, Mohammad A Jafri, Mohiuddin K Warsi, Muhammad I Naseer, Mohammed H Al-Qahtani

P72 Function predication of hypothetical proteins from genome database of chlamydia trachomatis

Rubi, Kundan Kumar, Ahmad AT Naqvi, Faizan Ahmad, Md I Hassan, Mohammad S Jamal, Mahmood Rasool, Mohammed H AlQahtani

P73 Transcription factors as novel molecular targets for skin cancer

Ashraf Ali, Jummanah Jarullah, Mahmood Rasool, Abdelbasit Buhmeida, Shahida Khan, Ghufrana Abdussami, Maryam Mahfooz, Mohammad A Kamal, Ghazi A Damanhouri, Mohammad S Jamal

P74 An In Silico analysis of Plumbagin binding to apoptosis executioner: Caspase-3 and Caspase-7

Bushra Jarullah, Jummanah Jarullah, Mohammad SS Jarullah, Ashraf Ali, Mahmood Rasool, Mohammad S Jamal

P75 Single cell genomics applications for preimplantation genetic screening optimization: Comparative analysis of whole genome amplification technologies

Mourad Assidi, Muhammad Abu-Elmagd, Osama Bajouh, Peter Natesan Pushparaj, Mohammed Al-Qahtani, Adel Abuzenadah

P76 ZFP36 regulates miRs-34a in anti-IgM triggered immature B cells

Mohammad S Jamal, Jummanah Jarullah, Abdulah EA Mathkoor, Hashim MA Alsalmi, Anas MM Oun, Ghazi A Damanhauri, Mahmood Rasool, Mohammed H AlQahtani

P77 Identification of a novel mutation in the STAMBP gene in a family with microcephaly-capillary malformation syndrome

Muhammad I. Naseer, Mahmood Rasool, Sameera Sogaty, Adeel G. Chudhary, Yousif A. Abutalib, Daniele Merico, Susan Walker, Christian R. Marshall, Mehdi Zarrei, Stephen W. Scherer, Mohammad H. Al-Qahtani

P78 Copy number variations in Saudi patients with intellectual disability and epilepsy

Muhammad I. Naseer, Muhammad Faheem, Adeel G. Chaudhary, Mahmood Rasool, Gauthaman Kalamegam, Fai Talal Ashgan, Mourad Assidi, Farid Ahmed, Syed Kashif Zaidi, Mohammed M. Jan, Mohammad H. Al-Qahtani

P79 Prognostic significance of CD44 expression profile in colorectal carcinoma

Maryam Al-Zahrani, Sahira Lary, Sahar Hakamy, Ashraf Dallol, Mahmoud Al-Ahwal, Jaudah Al-Maghrabi, Emmanuel Dermitzakis, Adel Abuzenadah, Abdelbaset Buhmeida, Mohammed Al-Qahtani

P80 Association of the endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications

Abeer A Al-refai, Mona Saleh, Rehab I Yassien, Mahmmoud Kamel, Rabab M Habeb

P81 SNPs array to screen genetic variation among diabetic patients

Najlaa Filimban, Ashraf Dallol, Nadia Ghannam, Mohammed Al-Qahtani, Adel Mohammed Abuzenadah

P82 Detection and genotyping of Helicobacter pylori among gastric cancer patients from Saudi Arabian population

Fehmida Bibi, Sana Akhtar, Esam I. Azhar, Muhammad Yasir, Muhammad I. Nasser, Asif A. Jiman-Fatani, Ali Sawan

P83 Antimicrobial drug resistance and molecular detection of susceptibility to Fluoroquinolones among clinical isolates of Salmonella species from Jeddah-Saudi Arabia

Ruaa A Lahzah, Asho Ali

P84 Identification of the toxic and virulence nature of MAP1138c protein of Mycobacterium avium subsp. paratuberculosis

Syed A Hassan, Seyed E Hasnain, Iftikhar A Tayubi, Hamza A Abujabal, Alaa O Magrabi

P85 In vitro and in silico evaluation of miR137 in human breast cancer

Fazal Khan, Gauthaman Kalamegam, Peter Natesan Pushparaj, Adel Abuzenada, Taha Abduallah Kumosani, Elie Barbour, Mohammed Al-Qahtani

P86 Auruka gene is over-expressed in Saudi breast cancer

Manal Shabaad, Shilu Mathew, Ashraf Dallol, Adnan Merdad, Abdelbaset Buhmeida, Mohammed Al-Qahtani

P87 The potential of immunogenomics in personalized healthcare

Mourad Assidi, Muhammad Abu-Elmagd, Kalamegam Gauthaman, Mamdooh Gari, Adeel Chaudhary, Adel Abuzenadah, Peter Natesan Pushparaj, Mohammed Al-Qahtani

P88 In Silico physiochemical and structural characterization of a putative ORF MAP0591 and its implication in the pathogenesis of Mycobacterium paratuberculosis in ruminants and humans

Syed A Hassan, Iftikhar A Tayubi, Hani MA Aljahdali

P89 Effects of heat shock on human bone marrow mesenchymal stem cells (BM-MSCs): Implications in regenerative medicine

Reham Al Nono, Mamdooh Gari, Haneen Alsehli, Farid Ahmed, Mohammed Abbas, Gauthaman Kalamegam, Mohammed Al-Qahtani

P90 In Silico analyses of the molecular targets of Resveratrol unravels its importance in mast cell mediated allergic responses

Shilu Mathew, Fazal Khan, Mahmood Rasool, Mohammed Sarwar Jamal, Muhammad Imran Naseer, Zeenat Mirza, Sajjad Karim, Shakeel Ansari, Mourad Assidi, Gauthaman Kalamegam, Mamdooh Gari, Adeel Chaudhary, Adel Abuzenadah, Peter Natesan Pushparaj, Mohammed Al-Qahtani

P91 Effects of environmental particulate matter on bone-marrow mesenchymal stem cells

Muhammad Abu-Elmagd, Gauthaman Kalamegam, Roaa Kadam, Mansour A Alghamdi, Magdy Shamy, Max Costa, Mamdouh I Khoder, Mourad Assidi, Peter Natesan Pushparaj, Mamdooh Gari, Mohammed Al-Qahtani

P92 Distinctive charge clusters in human virus proteomes

Najla Kharrat, Sabrine Belmabrouk, Rania Abdelhedi, Riadh Benmarzoug, Mourad Assidi, Mohammed H. Al Qahtani, Ahmed Rebai

P93 In vitro experimental model and approach in identification of new biomarkers of inflammatory forms of arthritis

Ghazi Dhamanhouri, Peter Natesan Pushparaj, Abdelwahab Noorwali, Mohammad Khalid Alwasiyah, Afnan Bahamaid, Saadiah Alfakeeh, Aisha Alyamani, Haneen Alsehli, Mohammed Abbas, Mamdooh Gari, Ali Mobasheri, Gauthaman Kalamegam, Mohammed Al-Qahtani

P94 Molecular docking of GABAA receptor subunit γ-2 with novel anti-epileptic compounds

Muhammad Faheem, Shilu Mathew, Peter Natesan Pushparaj, Mohammad H. Al-Qahtani

P95 Breast cancer knowledge, awareness, and practices among Saudi females residing in Jeddah

Shilu Mathew, Muhammad Faheem, Shiny Mathew, Peter Natesan Pushparaj, Mohammad H. Al-Qahtani

P96 Anti-inflammatory role of Sesamin by Attenuation of Iba1/TNF-α/ICAM-1/iNOS signaling in Diabetic Retinopathy

Mohammad Sarwar Jamal, Syed Kashif Zaidi, Raziuddin Khan, Kanchan Bhatia, Mohammed H. Al-Qahtani, Saif Ahmad

P97 Identification of drug lead molecule against vp35 protein of Ebola virus: An In-Silico approach

Iftikhar AslamTayubi, Manish Tripathi, Syed Asif Hassan, Rahul Shrivastava

P98 An approach to personalized medicine from SNP-calling through disease analysis using whole exome-sequencing of three sub-continental populations

Iftikhar A Tayubi, Syed Hassan, Hamza A.S Abujabal

P99 Low versus high frequency of Glucose –6 – Phosphate Dehydrogenase (G6PD) deficiency in urban against tribal population of Gujarat – A signal to natural selection

Ishani Shah, Bushra Jarullah, Mohammad S Jamal, Jummanah Jarullah

P100 Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update

Ishfaq A Sheikh, Ejaz Ahmad, Mohammad S Jamal, Mohd Rehan, Muhammad Abu-Elmagd, Iftikhar A Tayubi, Samera F AlBasri, Osama S Bajouh, Rola F Turki, Adel M Abuzenadah, Ghazi A Damanhouri, Mohd A Beg, Mohammed Al-Qahtani

P101 Prevalence of congenital heart diseases among Down syndrome cases in Saudi Arabia: role of molecular genetics in the pathogenesis

Sahar AF Hammoudah, Khalid M AlHarbi, Lama M El-Attar, Ahmed MZ Darwish

P102 Combinatorial efficacy of specific pathway inhibitors in breast cancer cells

Sara M Ibrahim, Ashraf Dallol, Hani Choudhry, Adel Abuzenadah, Jalaludden Awlia, Adeel Chaudhary, Farid Ahmed, Mohammed Al-Qahtani

P103 MiR-143 and miR-145 cluster as potential replacement medicine for the treatment of cancer

Mohammad A Jafri, Muhammad Abu-Elmagd, Mourad Assidi, Mohammed Al-Qahtani

P104 Metagenomic profile of gut microbiota during pregnancy in Saudi population

Imran khan, Muhammad Yasir, Esam I. Azhar, Sameera Al-basri, Elie Barbour, Taha Kumosani

P105 Exploration of anticancer targets of selected metabolites of Phoenix dactylifera L. using systems biological approaches

Fazal Khan, Gauthaman Kalamegam, Peter Natesan Pushparaj, Adel Abuzenada, Taha Abduallah Kumosani, Elie Barbour

P106 CD226 and CD40 gene polymorphism in susceptibility to Juvenile rheumatoid arthritis in Egyptian patients

Heba M. EL Sayed, Eman A. Hafez

P107 Paediatric exome sequencing in autism spectrum disorder ascertained in Saudi families

Hans-Juergen Schulten, Aisha Hassan Elaimi, Ibtessam R Hussein, Randa Ibrahim Bassiouni, Mohammad Khalid Alwasiyah, Richard F Wintle, Adeel Chaudhary, Stephen W Scherer, Mohammed Al-Qahtani

P108 Crystal structure of the complex formed between Phospholipase A2 and the central core hydrophobic fragment of Alzheimer’s β- amyloid peptide: a reductionist approach

Zeenat Mirza, Vikram Gopalakrishna Pillai, Sajjad Karim, Sujata Sharma, Punit Kaur, Alagiri Srinivasan, Tej P Singh, Mohammed Al-Qahtani

P109 Differential expression profiling between meningiomas from female and male patients

Reem Alotibi, Alaa Al-Ahmadi, Fatima Al-Adwani, Deema Hussein, Sajjad Karim, Mona Al-Sharif, Awatif Jamal, Fahad Al-Ghamdi, Jaudah Al-Maghrabi, Saleh S Baeesa, Mohammed Bangash, Adeel Chaudhary, Hans-Juergen Schulten, Mohammed Al-Qahtani

P110 Neurospheres as models of early brain development and therapeutics

Muhammad Faheem, Peter Natesan Pushparaj, Shilu Mathew, Taha Abdullah Kumosani, Gauthaman Kalamegam, Mohammed Al-Qahtani

P111 Identification of a recurrent causative missense mutation p.(W577C) at the LDLR exon 12 in familial hypercholesterolemia affected Saudi families

Faisal A Al-Allaf, Zainularifeen Abduljaleel, Abdullah Alashwal, Mohiuddin M. Taher, Abdellatif Bouazzaoui, Halah Abalkhail, Faisal A. Ba-Hammam, Mohammad Athar

P112 Epithelial ovarian carcinoma (EOC): Systems oncological approach to identify diagnostic, prognostic and therapeutic biomarkers

Gauthaman Kalamegam, Peter Natesan Pushparaj, Muhammad Abu-Elmagd, Farid Ahmed Khalid HussainWali Sait, Nisreen Anfinan, Mamdooh Gari, Adeel Chaudhary, Adel Abuzenadah, Mourad Assidi, Mohammed Al-Qahtani

P113 Crohn’s disease phenotype in northern Tunisian population

Naira Ben Mami, Yosr Z Haffani, Mouna Medhioub, Lamine Hamzaoui, Ameur Cherif, Msadok Azouz

P114 Establishment of In Silico approaches to decipher the potential toxicity and mechanism of action of drug candidates and environmental agents

Gauthaman Kalamegam, Fazal Khan, Shilu Mathew, Mohammed Imran Nasser, Mahmood Rasool, Farid Ahmed, Peter Natesan Pushparaj, Mohammed Al-Qahtani

P115 1q Gain predicts poor prognosis marker for young breast cancer patients

Shereen A Turkistany, Lina M Al-harbi, Ashraf Dallol, Jamal Sabir, Adeel Chaudhary, Adel Abuzenadah

P116 Disorders of sex chromosomes in a diagnostic genomic medicine unit in Saudi Arabia: Prevalence, diagnosis and future guidelines

Basmah Al-Madoudi, Bayan Al-Aslani, Khulud Al-Harbi, Rwan Al-Jahdali, Hanadi Qudaih, Emad Al Hamzy, Mourad Assidi, Mohammed Al Qahtani

P117 Combination of WYE354 and Sunitinib demonstrate synergistic inhibition of acute myeloid leukemia in vitro

Asad M Ilyas, Youssri Ahmed, Mamdooh Gari, Farid Ahmed, Mohammed Alqahtani

P118 Integrated use of evolutionary information in GWAS reveals important SNPs in Asthma

Nada Salem, Sajjad Karim, Elham M Alhathli, Heba Abusamra, Hend F Nour Eldin, Mohammed H Al-Qahtani, Sudhir Kumar

P119 Assessment of BRAF, IDH1, IDH2, and EGFR mutations in a series of primary brain tumors

Fatima Al-Adwani, Deema Hussein, Mona Al-Sharif, Awatif Jamal, Fahad Al-Ghamdi, Jaudah Al-Maghrabi, Saleh S Baeesa, Mohammed Bangash, Adeel Chaudhary, Mohammed Al-Qahtani, Hans-Juergen Schulten

P120 Expression profiles distinguish oligodendrogliomas from glioblastoma multiformes with or without oligodendroglioma component

Alaa Alamandi, Reem Alotibi, Deema Hussein, Sajjad Karim, Jaudah Al-Maghrabi, Fahad Al-Ghamdi, Awatif Jamal, Saleh S Baeesa, Mohammed Bangash, Adeel Chaudhary, Hans-Juergen Schulten, Mohammed Al-Qahtani

P121 Hierarchical clustering in thyroid goiters and hyperplastic lesions

Ohoud Subhi, Nadia Bagatian, Sajjad Karim, Adel Al-Johari, Osman Abdel Al-Hamour, Hosam Al-Aradati, Abdulmonem Al-Mutawa, Faisal Al-Mashat, Jaudah Al-Maghrabi, Hans-Juergen Schulten, Mohammad Al-Qahtani

P122 Differential expression analysis in thyroiditis and papillary thyroid carcinomas with or without coexisting thyroiditis

Nadia Bagatian, Ohoud Subhi, Sajjad Karim, Adel Al-Johari, Osman Abdel Al-Hamour, Abdulmonem Al-Mutawa, Hosam Al-Aradati, Faisal Al-Mashat, Mohammad Al-Qahtani, Hans-Juergen Schulten, Jaudah Al-Maghrabi

P123 Metagenomic analysis of waste water microbiome in Sausdi Arabia

Muhammad W shah, Muhammad Yasir, Esam I Azhar, Saad Al-Masoodi

P124 Molecular characterization of Helicobacter pylori from faecal samples of Tunisian patients with gastric cancer

Yosr Z Haffani, Msadok Azouz, Emna Khamla, Chaima Jlassi, Ahmed S. Masmoudi, Ameur Cherif, Lassaad Belbahri

P125 Diagnostic application of the oncoscan© panel for the identification of hereditary cancer syndrome

Shadi Al-Khayyat, Roba Attas, Atlal Abu-Sanad, Mohammed Abuzinadah, Adnan MerdadAshraf Dallol, Adeel Chaudhary, Mohammed Al-Qahtani, Adel Abuzenadah

P126 Characterization of clinical and neurocognitive features in a family with a novel OGT gene missense mutation c. 1193G > A/ (p. Ala319Thr)

Habib Bouazzi, Carlos Trujillo, Mohammad Khalid Alwasiyah, Mohammed Al-Qahtani

P127 Case report: a rare homozygous deletion mutation of TMEM70 gene associated with 3-Methylglutaconic Aciduria and cataract in a Saudi patient

Maha Alotaibi, Rami Nassir

P128 Isolation and purification of antimicrobial milk proteins

Ishfaq A Sheikh, Mohammad A Kamal, Essam H Jiffri, Ghulam M Ashraf, Mohd A Beg

P129 Integrated analysis reveals association of ATP8B1 gene with colorectal cancer

Mohammad A Aziz, Rizwan Ali, Mahmood Rasool, Mohammad S Jamal, Nusaibah samman, Ghufrana Abdussami, Sathish Periyasamy, Mohiuddin K Warsi, Mohammed Aldress, Majed Al Otaibi, Zeyad Al Yousef, Mohamed Boudjelal, Abdelbasit Buhmeida, Mohammed H Al-Qahtani, Ibrahim AlAbdulkarim

P130 Implication of IL-10 and IL-28 polymorphism with successful anti-HCV therapy and viral clearance

Rubi Ghazala, Shilu Mathew, M. Haroon Hamed, Mourad Assidi, Mohammed Al-Qahtani, Ishtiaq Qadri

P131 Interactions of endocrine disruptor di-(2-ethylhexyl) phthalate (DEHP) and its metabolite mono-2-ethylhexyl phthalate (MEHP) with progesterone receptor

Ishfaq A Sheikh, Muhammad Abu-Elmagd, Rola F Turki, Ghazi A Damanhouri, Mohd A. Beg

P132 Association of HCV nucleotide polymorphism in the development of hepatocellular carcinoma

Mohd Suhail, Abid Qureshi, Adil Jamal, Peter Natesan Pushparaj, Mohammad Al-Qahtani, Ishtiaq Qadri

P133 Gene expression profiling by DNA microarrays in colon cancer treated with chelidonine alkaloid

Mahmoud Z El-Readi, Safaa Y Eid, Michael Wink

P134 Successful in vitro fertilization after eight failed trials

Ahmed M. Isa, Lulu Alnuaim, Johara Almutawa, Basim Abu-Rafae, Saleh Alasiri, Saleh Binsaleh

P135 Genetic sensitivity analysis using SCGE, cell cycle and mitochondrial membrane potential in OPs stressed leukocytes in Rattus norvegicus through flow cytometric input

Nazia Nazam, Mohamad I Lone, Waseem Ahmad, Shakeel A Ansari, Mohamed H Alqahtani

O1 Regulation of genes by telomere length over long distances

Jerry W. Shay

University of Texas Southwestern Medical Center, Dallas, Texas, USA

The ends of linear chromosomes are called telomeres that resemble broken DNA. However, the telomeres are protected from the DNA damage responses due to the formation of a looping structure (T-loop) and by “capping” the telomeres with a series of shelterin proteins. It is generally thought the main, if not only, function of telomeres is protection from DNA damage responses. When telomeres get very short due to normal replicative aging, cells stop dividing due to loss of the telomere end protective functions. We have previously reported that telomeres may also have additional functions in human cells. Telomeres are characterized by a distinct chromatin structure with spreading of heterochromatin into the subtelomeric regions, but little is known about the chromatin conformation of human telomeres. We have previously shown, using a luciferase reporter introduced into telomeres, that there is a 10-fold decreased expression of the reporter compared to the reporter introduced into internal genomic loci. This phenomenon is known as Telomere Position Effects (TPE). We have also found that a human gene, interferon stimulating gene 15 (ISG15), (~1 M base pairs from the 1p36.33 telomere) is silenced in young cells with long telomerase, upregulated in cells with short telomeres and silenced again in old cells with experimentally hTERT (telomerase) elongated telomeres. However, we observed genes between ISG15 and the telomere are not regulated by classic telomere position effects (TPE). To distinguish this type of telomere length dependent regulation of gene expression from classic TPE, we have termed this type of regulation Telomere Position Effects Over Long Distances (TPE-OLD). We discovered using 3D co-FISH and a modification of Hi-C (chromosome capture followed by high-throughput sequencing), that there are a significant number of genes within the first 10 M bases distal to the telomere on many chromosomes regulated by telomere length with genes closer to the telomere not being regulated by TPE.

O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy

Noriko Homma1, Ruyun Zhou1, Muhammad Imran Naseer2, Adeel G. Chaudhary2, Mohammed Al-Qahtani2, Nobutaka Hirokawa1,2

1Department of Cell Biology and Anatomy, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan; 2Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

Correspondence: Nobutaka Hirokawa (hirokawa@m.u-tokyo.ac.jp) – Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

Kinesin super family protein 2A (KIF2A) is an ATP-dependent microtubule destabilizer, that belongs to the kinesin-13 family. It is highly expressed in juvenile brains, but its postnatal function has not been determined due to mortality in KIF2A-deficient mice. In addition, KIF2A is a causal gene in human Malformation of Cortical Development (MCD) with epilepsy, but the contribution of KIF2A to its pathogenesis is not yet understood due to the small number of human patients. In this study, we first analyzed the prenatal function of KIF2A using kif2a-KO mice. These mice were pale, breathed irregularly, and exhibited frequent twitching in addition to malformations resembling those in kif2a-mutated human patients. To determine the post-migration function of KIF2A, we generated newly tamoxifen-inducible conditional knockout mice. Despite successful neuronal migration, all offspring displayed hyper-activity, weight loss, severe cortical/hippocampal-focus epilepsy, and died. Interestingly, KIF2A was highly expressed in excitatory axons, in cortical neurites in layers II/III/V and in dentate mossy fibers (MF). In the cortex, the loss of KIF2A generated aberrant axon sprouting in those layers. In the hippocampus, the loss of KIF2A resulted in the development of hippocampal sclerosis, MF sprouting, and recurrent excitatory circuits resembling but different from TLE. These phenotypes developed without excitation. cKO granule cells exhibited failed axon/dendrite determination, and developed multiple short axons throughout the entire molecular layer. These results suggest that KIF2A is crucial postnatally for establishing accurate neuronal circuits, in addition to its role in prenatal cell survival, migration, and axon elongation.

O3 Integration of metagenomics and metabolomics in gut microbiome research

Maryam Goudarzi1 and Albert J. Fornace Jr.1,2,3,4

1Department of Biochemistry and Molecular & Cellular Biology, Lombardi Comprehensive Cancer Center. Georgetown University, Washington, DC, USA; 2Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; 3Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; 4Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, KSA

Correspondence: Albert J. Fornace Jr. (af294@georgetown.edu) – Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, KSA

The gut is the largest reservoir of microbes in the body, harboring more than 100 trillion microorganisms in a well-balanced communication with the host factors. The gut microbiota plays an essential role in a wide range of biological functions such as digestion and the development of immunological responses. The microbial community composition and diversity is important in maintaining the homeostatis in the host. Factors, which may influence the gut microbial composition include diet, environmental exposures, age, genetics, and many more. Recent advances in technology, particularly 16S rRNA sequencing and mass spectrometry have enabled us to survey these microbial communities at the phylogenetic level and assess the host/microbes co-metabolism. The metagenomic studies have shed light on the functional composition of the gut microbiota and have determined that in diseases such as inflammatory bowel disease (IBD) there is an increase in functions of the auxotrophic and pathobiont bacteria. A number of studies have also pointed to an increase in the sulfate-reducing bacteria, such as Desulfovibrio, in IBD. On the other hand, metabolomics studies have revealed that taurine-conjugated bile acids increase the availability of free sulfur causing an expansion of the sulfate-reducing pathobiont Bilophila wadsworthia, which drive colitis in genetically susceptible IL10 −/− but not wild-type mice. Furthermore, an increased in glutathione transport and riboflavin metabolism and a decrease in biosynthesis of amino acids have been reported in ulcerative colitis patients, which is indicative of increased predisposition for managing oxidative stress, a hallmark of an inflammatory environment. Our current studies have explored the correlative nature of the microbe/host co-metabolism to characterize the regulatory role of microbiota in maintaining host health. These correlative host/microbial studies have the potential to determine causality, response to treatment, risk prediction, and keystone species for use as probiotics in diseases such as IBD or colitis induced by immuno-radiotherapy.

O4 A unique integrated system to discern pathogenesis of central nervous system tumors

Saleh Baeesa, Deema Hussain, Mohammed Bangash, Fahad Alghamdi, Hans-Juergen Schulten, Angel Carracedo, Ishaq Khan, Hanadi Qashqari, Nawal Madkhali, Mohamad Saka, Kulvinder S. Saini, Awatif Jamal, Jaudah Al-Maghrabi, Adel Abuzenadah, Adeel Chaudhary, Mohammed Al Qahtani and Ghazi Damanhouri

King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence: Deema Hussain (deemah@hotmail.com) – King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia

Central Nervous System Tumors (CNST) are a collection of neoplasms that grow in the brain and the spinal cord. Long term survival for patients carrying these tumors can reach at best 14 % in countries that provide optimal health operating systems. Despite advancement in cancer targeted therapy, surgery and radiation remain typically the main methods of treatment, even though both are challenging and may affect the quality of life of survivors adversely. Inventive approaches and deeper comprehensions of tumor characteristics are needed to transform treatment options for CNST patients. We established a unique integrated system to enable analysis of multiple bio-parameters of individual CNST. Each sample recovered was prepared to preserve tissue and generate a corresponding cell line with a purpose to process for genetic, biochemical, cytological and pharmacological analysis. A collection of 84 tumors were recovered, with a wide range of tumor types including Meningiomas, Astrocytomas, Oligodendrogliomas, Medulloblastomas and Glioblastomas. Generating a tumor type combined outlook facilitated access to vital information, as exemplified by the analysis of sixteen primary Meningiomas. Investigating the gene expression profile of uncultured tumors samples while considering the live cell behavior in relation to morphology, growth, stemness and sensitivity to chemotherapy, enabled the identification of possible novel prognostic markers for Meningiomas, including the recently associated cancer stem cell marker Anterior Gradient 2 Homolog (AGR2). This integrated analysis approach is critical for the development of safe, efficacious and potent targeted therapeutic modalities.

O5 RPL27A is a target of miR-595 and deficiency contributes to ribosomal dysgenesis

Heba Alkhatabi

Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

Myelodysplasia with monosomy 7 or deletion 7q has a dismal prognosis and high propensity for leukaemic transformation. The exact pathogenesis of these disorders remains elusive. We investigated functional consequences of deletion of microRNAs (miRNAs) residing on chromosome 7q, focusing on miR-595. Using a novel assay, several targets for miR-595 were identified, including a large ribosomal subunit RPL27A. RPL27A downregulation induced p53 activation, apoptosis and inhibited proliferation. Importantly, p53-independent effects were identified secondary to a reduction in the ribosome subunit 60s with associated ribosome dysgenesis. Of note, RPL27A overexpression showed no significant effects on p53 mRNA levels but did enhance proliferation. In normal CD34+ cells, RPL27A knockdown preferentially blocked erythroid proliferation and differentiation. Lastly, miR-595 appears significantly downregulated in MDS patient samples possessing -7/-7q anomalies compared to those with normal karyotype. We postulate that haploinsufficency of miR-595 in patients with -7/del 7q may contribute to disease pathogenesis via RPL27A modulation.

O6 Next generation DNA sequencing panels for haemostatic and platelet disorders and for Fanconi anaemia in routine diagnostic service

Anne Goodeve, Laura Crookes, Nikolas Niksic, Nicholas Beauchamp

Sheffield Diagnostic Genetic Service, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield, UK

Correspondence: Anne Goodeve (a.goodeve@sheffield.ac.uk) – Sheffield Diagnostic Genetic Service, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield, UK

Next Generation sequencing (NGS) is transforming delivery of diagnostic molecular genetics. Gene panels are being utilised to analyse groups of related disorders and to extend diagnostic capability in comparison with previous Sanger sequencing. The aim of this study is to examine the utility of gene panels for diagnostic/research NGS analysis of haemostatic and platelet disorders and for Fanconi anaemia. Requests were received for all but one (F5) genes on the haemostasis/platelet panel. Candidate pathogenic mutations were identified in 24 of 39 patients (62 %), including 15/16 males diagnosed with haemophilia A and 3/7 individuals with possible von Willebrand disease. Some analyses (e.g. ADAMTS13, MYH9, VWF) were requested to help exclude specific diagnoses. In addition to analysis of single genes, combinations were analysed simultaneously, e.g. F8 & F9 (possible carrier relative of deceased haemophilia patient; unknown type); F8, F9, F13A1, F13B and VWF (baby died of bleeding shortly after birth), F8 & VWF (low FVIII:C). In contrast, nearly all patients referred for FA analysis were seeking a diagnosis of the disorder and all 16 genes were analysed in most individuals investigated (15/19). Biallelic mutations were identified in 7 cases (33 %) in BRCA2, FANCA, FANCC, FANCD2 and FANCG. A single heterozygous mutation was identified in 2 patients (13 %), 2 heterozygous mutations in different genes in 1 case (7 %), homozygous mutations in 2 (13 %) and no mutation in 5 (33 %). We can conclude that NGS provides a single laboratory workflow for analysis of gene panels for related disorders as well as for whole genomes/exomes. Data analysis can include a single gene, such as ADAMTS13, or ≥ 1 gene for disorders such as those affecting fibrinogen. For disorders potentially caused by one of the several genes in a pathway such as FA, all can be analysed simultaneously. Use of NGS provides a single laboratory workflow for analysis of gene panels for many different disorders and can dramatically reduce time to achieve a definitive diagnosis.

O7 Targeted sequencing panels and their utilization in personalized medicine

Adel M. Abuzenadah

Center of Innovations in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Several milestones have to be achieved in order to introduce the concept of personalized medicine to the healthcare system in Saudi Arabia. There is a notable lack of publicly available information about the “normal” genetic makeup of this population which is hindering the complete elucidation of “disease” genomes. Therefore, it is important that considerable effort should be spent on the identification of the genetic and epigenetic risk factors that predispose to the common diseases in the Kingdom of Saudi Arabia. Knowledge gained will help in the elucidation of disease biomarkers and drug response modifiers. Furthermore, providers of personalized medicine should validate internationally-approved biomarkers and risk factor indicators for use in the Kingdom of Saudi Arabia. Most importantly, genetic tests offered to the public should be designed to be cost-effective without compromising sensitivity or specificity and with fast turnaround amenable to use in the clinic. Towards this end, we at the Center of Innovations in Personalized Medicine (CIPM) at King Abdulaziz University are utilizing the robustness of the Ion Torrent Personal Genome Machine to design genetic tests for afflictions common to the Kingdom of Saudi Arabia. We have designed and tested custom Ampliseq panels as well as used panels from the Life Technologies catalog. Our array of targeted sequencing panel now covers conditions such as deafness, beta-thalassemia, thrombophilia, inborn errors of metabolism, and cancer susceptibility. We will report on the progress achieved so far and discuss the future of such platform in the delivery of individualized diagnostics.

O8 International biobanking in the era of precision medicine

Jim Vaught

President, ISBER, Editor-in-Chief, Biopreservation & Biobanking, USA

Biospecimens are collected from patients and other donors in a variety of ways for basic, clinical and epidemiologic research studies. Methods for collecting, processing, storing and analyzing biospecimens have usually been developed locally for diagnostic and research purposes, with little consideration for standardization or long-term quality management. Biospecimen management has developed into a more scientifically-based endeavor, as researchers have realized that biospecimens and data of consistent quality are required as we enter the era of precision medicine.

Best practices have been developed by organizations such as the International Society for Biological and Environmental and Repositories (ISBER), the U.S. National Cancer Institute (NCI), the International Agency for Research on Cancer (IARC) and the European Organization for Economic Cooperation and Development (OECD). Biospecimen research programs have been developed to establish evidence-based standard procedures to control the collection and processing of biospecimens. Molecular data from the analysis of biospecimens contribute directly to the diagnosis of disease and treatment of patients. Various “pre-analytical” variables can affect the quality of biospecimens. Among these variables are: the amount of time that it takes for surgical removal of the biospecimen; the time the specimen spends at room temperature before it is frozen or fixed with formalin; and many other variables that can affect biospecimen quality. There is the potential for: incorrect diagnoses; incorrect treatment; irreproducible results; and overall the potential for misinterpretation of artifacts as new biomarkers. The adoption of best practices for biospecimen collection and processing is an important part of the strategy to advance translational research and precision medicine. These practices should include:
  • Governance models with clearly stated technical standards, ethical guidelines, access policies and procedures, scientific rationale, and long-term custodianship plans.

  • A strong quality management program with clearly defined standard operating procedures, and regular audits to assure compliance.

  • A comprehensive business model that has a sustainable cost-recovery plan, or a plan to assure consistent long-term financial support.

  • In general, adherence to a set of best practices governing both technical and ethical/legal issues.

The future development of international collaboration in biobanking will require cooperation among various nations to standardize and harmonize their biospecimen practices.

O9 Biobank and biodata for clinical and forensic applications

Bruce Budowle1,2, Mourad Assidi2, Abdelbaset Buhmeida2

1Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA; 2Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence: Bruce Budowle (bruce.budowle@unthsc.edu) – Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

With advances in molecular biology (i.e., OMICs) and computational capabilities, society is on the verge of demystifying the causes of diseases with an expectation of better diagnostics, prognostics, and possible therapeutics for health and well-being. However, forensic science (for 30 years) embraced the field of genetics and built an entire infrastructure relying on DNA typing from biospecimen collection to final results integrated under strict and formal quality assurance guidelines. Both the medical and forensic disciplines rely on the accumulation of big data to perform precision, or personalized, analyses. These two disciplines have built biobanks and/or databanks with different rationales, designs and governance. Databanks and databases can be exploited to harness the power of emerging technologies and either enable detection of putative genes or potential suspects, and promote development of innovative biomarkers and treatments. Both resources must provide value, have proper ethical/conduct governance, develop capabilities to store and retrieve samples and annotated data, and be managed and maintained. Medical databases typically are governed by institutions (often not government agencies, although constrained by laws) and can be either free to those who donate samples or consumers pay for tests. Samples and metadata are provided on a voluntary consent basis, and the resource may be available to many interested parties. Forensic databases are controlled by the government, access is limited to law enforcement, and sample donation often is mandatory. Medical and forensic big data resources, views of data sharing, experiences of both systems users are discussed. Another resource, the human microbiome, should be considered. The composition of the microbiome can affect health and well-being. Indeed, the microbiome may end up being a more flexible and dynamic manner to address aspects of personalized medicine. Forensic genetics also may benefit as the microbes may serve as genetic signatures that could individualize humans and serve as another powerful identification tool. Forensic and medical biobanks should begin considering on how to sample, collect and store such samples in suitable core facilities, the microbiome banks. Such integration of the microbiome to either forensic and/or medical biobanks will revolutionize current approaches towards individualized medicine and precision forensics.

O10 Tissue microarray technique: a powerful adjunct tool for molecular profiling of solid tumors

Jaudah Al-Maghrabi

Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Tissue microarray (TMA) is one of the most revolutionary technologies introduced into research and routine laboratories during the past decade. It is based on the idea of applying miniaturization and a high throughput approach for tissue analysis. TMA is a method of harvesting small disks of tissue from a range of standard histological sections and placing them in an array on a recipient paraffin block such that hundreds of cases can be analysed simultaneously saving money and time. In this presentation we will go through the guidelines for conducting TMA, Advantages and disadvantages of TMA and we will present our experience of TMA establishment in Saudi Arabia. In the Kingdom of Saudi Arabia remains the Tissue Microarray “TMA” technique almost absent in the laboratories of pathology, at least, to our knowledge, in the western region of the Kingdom, and therefore, this project will contribute in principle to establish this modern technology, to help reduce expenses for materials and reagents used in research conducted in the field of cancer. So far, we successfully transferred approximately 7723 FFPE blocks of different types of solid tumors which, already archived at department of pathology, KAUH, during the last two decades to approximately 180 TMA FFPE Blocks. In addition, we validated and estimated the concordance rate between conventional FFPE full section and TMA FFPE slides which, was realistic and of good quality. Moreover, we also validated the TMA technique in an integrative and comprehensive approach with immunohistochemistry (IHC) for protein profiling of different markers and Bright-field double in situ hybridization (BDISH) for gene profiling in different solid tumors. The TMA technique seems to us as feasible, reasonable, doable and multipurpose. However, hard work is considered necessary to procure the associated clinic-pathologic and follow up data of these samples to make the full package constructive and valuable for the scientists and research community for further downstream molecular profiling and characterization of solid tumors in order to initiate a basic platforms (infrastructure) for prognostic and predictive genomic models (molecular signatures) to facilitate the approach towards personalized oncology in Saudi Health System.

O11 The CEGMR biobanking unit: achievements, challenges and future plans

Abdelbaset Buhmeida1, Mourad Assidi1 and Leena Merdad2

1Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Dental Public Health, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence: Abdelbaset Buhmeida (abuhme@utu.fi) – Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

Since the achievement of the Human Genome Project in 2003, a significant increase in biobanks in terms of number, design, scale and governance has been noticed worldwide in order to support effective genomic research. Biobanks/Biorepositories are the main core around which OMICs scale research and advanced clinical applications have been performed to drive the Precision Medicine wave toward shaping the future of human welfare. Consequently, a biobanking unit has been developed at the Center of Excellence in Genomic Medicine (CEGMR) in 2008 to collect, store and release high quality biospecimens with fully annotated clinico-pathological data according to best practices established worldwide in order to deliver personalized diagnostics and tailor individualized therapeutics for the Saudi population. Despite promising milestones and over 150 publications in ISI journals using CEGMR Biobank Unit (CBU) biospecimens, the awareness about biobanking and biospecimen donation remains the foremost challenge. Reaching the benefits of biobanks rely on an educated public and well trained healthcare providers that will enable the establishment of perpetual and comprehensive partnerships between several stakeholders involved in healthcare service. A survey conducted by our CBU team targeted healthcare students at King Abdulaziz University and showed that only 46 % of them have heard about the “Human Genome Project”. Surprisingly, 72 % of these future healthcare providers have never heard of the term “biobank” which was significantly correlated with lower willingness to donate biospecimens. Interestingly, around 50 % of healthcare students were willing to donate biospecimens and believed that it will advance medical research and benefit the whole society. Better general health status, previous blood donation and higher scores of biobanking knowledge were significantly associated with the willingness to donate (p-value = 0.048, p-value = 0.043 and p-value < 0.001, respectively). These findings highlight the urgency of developing a multidisciplinary awareness strategy to integrate biobanking and OMICs scale approaches in the healthcare students’ curricula, building up therefore well qualified healthcare providers’ competencies. Simultaneously, a suitable and lifelong public outreach program about biobanking tailored to the diverse communities in Saudi Arabia must be launched to ensure their effective involvement in the biobanking and precision medicine trend with adequate awareness about benefits and risks.

O12 Phylomedicine of tumors

Sudhir Kumar, Sayaka Miura, and Karen Gomez

Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA

Correspondence: Sudhir Kumar (s.kumar@temple.edu) – Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA

Comparative analysis of sequences is routinely employed in tracing the origins, patterns, and evolutionary relationships of homologous sequences from strains, populations, and species. Now, these analyses are poised to become key in oncology owing to escalating sequencing of tumors. They will reveal evolutionary history of clones that comprise tumors, patterns of sequence diversity, and tempo and mode of clonal evolution that underlie the origin and adaptive proliferation of cancerous cells. I will present results from our evaluation of the performance of many existing computational methods in correctly inferring tumor clones from multi-region sequencing data. I will also present our new methods for inferring clone and tumor histories, which establish that our new method accurately infers (a) clusters of variants (clonotypes) that comprise a tumor, (b) evolutionary tree of clonotypes, and (c) estimates of their relative frequencies in tumors. These methods are based on fundamental molecular evolutionary principles and they will greatly facilitate cancer-related research pursued by basic biologists and clinicians.

O13 Clinical implementation of pharmacogenomics for colorectal cancer treatment

Angel Carracedo1, Mahmood Rasool2

1Genomic Medicine Group- Galician Foundation of Genomic Medicine (SERGAS), CIBERER, University of Santiago de Compostela, Santiago de Compostela, Spain; 2Center of Excellence in Genomic Medicine, King Abdulaziz University, Jeddah, KSA

Correspondence: Angel Carracedo (angel.carracedo@usc.es) – Genomic Medicine Group- Galician Foundation of Genomic Medicine (SERGAS), CIBERER, University of Santiago de Compostela, Santiago de Compostela, Spain

Colorectal cancer (CRC) is the third most prevalent cancer in men and the second in women worldwide and although a great improvement in response rate and patient’s survival was recently achieved through the introduction of new-targeted agents in combination with standard fluoropyrimidines-based chemotherapeutic regimens, still adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Some biomarkers to guide CRC treatment have been developed and some of them are considered valid by the regulatory agencies and included in the technical sheet of the drugs but many others are still “probable valid” needed of additional validation and cost-efficiency studies. Some of the most promising biomarkers are still not translated to clinical practice nor approved by the agencies. In addition, there is a lack of integration in a common framework of biomarkers at different levels (germline, somatic, epigenetic) limiting translation and cost-efficiency analysis. Here we present a strategy for the translation to clinical practice of pharmacogenomic biomarkers to predict response (both efficacy and ADRs) and to guide treatment in colorectal cancer including previous valid biomarkers approved by EMA, probable biomarkers at germline and somatic level. The selected markers include variants at DNA level (sequence level and methylation markers) and RNA level (including miRNA). The use of specific CTC genomic alterations associated with treatment resistance and recurrence to guide the selection of target therapies in mCRC patients will be also discussed. The final goal is an integrative approach for a practical translation to clinical practice of CRC pharmacogenomics. To achieve this goal cost efficiency studies will be performed and a pilot project has been to organize workflow and optimize decision-making processes.

O14 From association to causality: translation of GWAS findings for genomic medicine

Ahmed Rebai

Laboratory of Molecular and Cellular Screening Processes (Bioinformatics Group), Centre of Biotechnology of Sfax, P.O. Box “1177”, Sfax, Tunisia

With the decrease of the cost of high throughput genotyping and sequencing, Genome wide Association Studies (GWAS) have become a good approach to identify sequence variations and mainly Single nucleotide polymorphisms (SNP) that are related to complex and common diseases. However, GWAS data allow only associational inference and is only able to identify sequence variants that are statistically associated with the disease status. The last seven years have seen an exponential growth in the number of GWAS which resulted in over 15 thousand associated Single Nucleotide polymorphisms (SNPs) identified in more than 2100 published studies. Although many statistical methods and algorithms have been developed to increase the power to detect association, testing causal relationship between the associated SNPs and the disease risk was not given much attention. A causal variant is a ‘mutation’ that contributes to an increase in risk to disease. Establishing causality from association is thus a challenging task, hindered by many complicating factors and remains a major concern in identifying genetic causes of common diseases, particularly for clinical translation of GWAS findings. In order to establish causality, we generally need intervention, which means not only observing the genotypes of some individuals but taking actions that can manipulate these genotypes, which can only be done in animal models. However, recent studies showed that, although we cannot estimate causal effects using observations alone, it is possible to use the classical framework of causality inference to get estimate of lower bounds for these effects. Here I build on recent works within the Bayesian networks modeling framework, to present an original approach to test causality based on observation data only. Based on standard GWAS data alone, this approach provides a measure for ranking causal effects of associated variants. The accuracy and stability of this measure is assessed and compared to other approaches. Selecting the most likely causal variants from GWAS results will allow the prioritization and designs of targeted experiments to unravel causal mechanisms underlying association and effective clinical translation of GWAS findings for genomic medicine, including individual risk prediction, advanced clinical strategies and personalized treatments.

O15 E-GRASP: an interactive database and web application for efficient analysis of disease-associated genetic information

Sajjad Karim1, Hend F Nour Eldin1, Heba Abusamra1, Elham M Alhathli1, Nada Salem1, Mohammed H Al-Qahtani1, and Sudhir Kumar1,2

1Center of Excellence in Genomic Medicine Research, King Abdulaziz University, PO Box 80216, Jeddah 21589, Saudi Arabia; 2Institute for Genomics and Evolutionary Medicine, Temple University (SERC 602A), Philadelphia, PA 19122, USA

Correspondence: Sajjad Karim (skarim1@kau.edu.sa) – Center of Excellence in Genomic Medicine Research, King Abdulaziz University, PO Box 80216, Jeddah 21589, Saudi Arabia

Genome-wide association study data is used widely to identify the genetic variants associated with complex traits or common disease. Genome-Wide Repository of Associations between SNPs and Phenotypes (GRASP) is a refined database, containing  8.87 million SNP associations reported in 2044 studies and ~178 thousand phenotypes, derived from GWAS data. GRASP v2.0 users face difficulties in access and correlation of SNPs with traits. Thus we aimed to design an interactive database providing detailed information of SNPs required for better data interpretation, communication between possible collaborators and new hypotheses to be generated. To develop a web application, we used ASP.net as front-end tool; SQL server, MatLab, D3.js, D3Plus.js and jQuery data table as back-end tools; JavaScript and Ajax for client-side purpose. MATLAB was used to analyse the statistical replication and evolutionary information of each SNPs and all SNPs were mapped to genome position of human genome build 38 (hg38) using LiftOver. We developed a new web application called E-GRASP using an advance tool and different filter code to retrieve and represent data in better way leading to fast and easy data analysis. We retrieved and retained all information of GRASP in E-GRASP and added new information including statistical replication and evolutionary information of each SNPs. E-GRASP provides information under following categories: (i) SNPs view- provides information about SNPid, PMID, P-value, chromosome, position, number of studies and phenotypes for each SNPs; (ii) Study view- explains about unique SNPs replication in each studies and phenotypes, and (iii) Evolutionary view- describes evolutionary information including E-value for SNP phenotype association, E-rank of the evolutionary rate and time span of the position retrieved from the “E-rank Web Server” for each SNP. Web application allows the users to computed P-rank and E-rank using P-value and E-value respectively for each phenotype of different studies. In conclusion, E-GRASP is more representative database with additional information of SNPs replication and evolutionary scores, facilitating the comprehensive qualitative and quantitative analysis. In future, we aim add complete data sets of studies available in GRASP and provide more filters to get refined information.

O16 The supercomputer facility “AZIZ” at KAU: utility and future prospects

Hossam Faheem

Fujitsu Technology Solutions International

Aziz is ranked No. 360 among the world’s Top 500 supercomputers. Aziz is also one of the top 10 supercomputers in Kingdom of Saudi Arabia. Primary objective of Aziz is to support growing number of researchers and scientists in King Abdul Aziz University and its partners across different geographical locations. The compute facility consists of high-end compute nodes; interconnect infrastructure, and storage capabilities. Compute nodes consist of a total of 496 nodes (11,904 cores) for running large parallel jobs as well as a large number of small parallel or serial jobs. 380 nodes are standard compute nodes (9120 cores) with 96 GB (4GB per core) for running the majority of mixed HPC applications. The remaining 112 high memory compute nodes (2688 cores) with 256 GB (10.6GB per core) are intended for applications that require large memory for their execution. 2 NVidia Tesla K20 GPGPU equipped compute nodes (2496 CUDA cores) with 96GB for running applications with the ability to use GPU-based accelerators. 2 Intel Phi 5110P Co-processor equipped compute nodes (120 Xeon phi cores) with 96GB for running applications with the ability to use MIC based accelerators. Storage space contains Fujitsu FEFS high-speed parallel file system of 2 PB acts as scratch space as well as storage for current running jobs. A total of 28 I/O servers and Infiniband as interconnect enable high speed non-blocking storage access to compute nodes. To address the needs of longer term storage capacity at KAU, a total of 6 PB of usable permanent storage solution was provided with automatic archival system. A NAS storage unit of total 22 TB usable space acts as home directory and application space for users. Infiniband network consists of Intel QDR which is used as interconnect connecting computing nodes and FEFS high-speed storage system. It Features like non-blocking configuration and RDMA enables application use full potential of underlying interconnect and reach maximum performance, delivering results in least possible time. We believe that Aziz will have a great effect on accelerating scientific research and solving computationally intensive problems at KAU.

O17 New research into the causes of male infertility

Ashok Agarwal

Case Western Reserve University, School of Medicine and Lerner College of Medicine, Cleveland Clinic Foundation; American Center for Reproductive Medicine, Andrology Center, Cleveland, Ohio, USA

Twenty-five percent of male-factor cases present with no identifiable cause of male infertility. Conventional semen analysis provides important but limited information in the laboratory diagnosis of male infertility. While advanced sperm function tests provide additional information at the cellular level, understanding the underlying molecular mechanism of sperm dysfunction is important. The talk will mainly focus on new research into the causes of male infertility. Proteomics is the new frontier of research in male infertility as it allows the identification of numerous sperm-specific proteins. In addition, it provides a greater understanding of protein functions involved in sperm processes such as motility, capacitation, acrosome reaction & fertilization. Identification of alterations in major proteins associated with dysfunctional sperm will help in our understanding of the pathology of male infertility. The speaker will examine, 1) the current methodology and techniques used in the global proteomic analysis of sperm and seminal plasma samples from infertile men with various clinical diagnosis, 2) examine the bioinformatics tools and search engines employed in analyzing the data; 3) discuss the key findings of recent proteomics research published from his center. Finally, the speaker will review the future of proteomics in male infertility and list the major challenges in introducing proteomics in the laboratory diagnosis of male infertility.

O18 The Klinefelter syndrome: recent progress in pathophysiology and management

Eberhard Nieschlag1,2, Joachim Wistuba1, Oliver S. Damm1, Mohd A. Beg2, Taha A. Abdel-Meguid3, Hisham A. Mosli3, Osama S. Bajouh4, Adel M. Abuzenadah2,5, Mohammed H. Al-Qahtani2

1Center for Reproductive Medicine and Andrology, University of Münster, Münster, Germany; 2Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Urology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia; 4Department of Obstetrics and Gynecology, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia; 5KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence: Eberhard Nieschlag (Eberhard.Nieschlag@ukmuenster.de) – Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

Background

The Klinefelter syndrome (KS), 47, XXY karyotype, is the most common chromosome aneuploidy in men characterized by hypogonadism, infertility, and other comorbidities. The incidence of KS in the general male population is 1:500, whereas in our ongoing project in Saudi Arabia the incidence is 1:11 in selected patients with azoospermia or low sperm counts.

Fertility

Until recently KS men were considered infertile as about 90 % of KS men are azoospermic. Recently, sperm were obtained by testicular sperm extraction for intracytoplasmic sperm injection into oocytes, resulting in live-born children. Most of these children have a euploid karyotype as these sperm derive from tubuli with euploid spermatogonial foci. As shown in a KS mouse model these spermatogonia get lost during early development so that cryopreservation of testicular biopsies from prepubertal boys for later gamete maturation in vitro is discussed.

Comorbidities

KS is often associated with gynecomastia, metabolic syndrome, diabetes type II, cardiopathies, thrombosis, embolism, osteoporosis, and epilepsy. Androgen receptor polymorphism influences the incidence and together with smaller diameter of arteries in KS may aggravate associated disorders. Paternal compared to maternal origin of X chromosome is associated with a more pronounced risk of insulin resistance, metabolic syndrome, and cardiac disorders.

Psycho-neurological function

Half of KS patients suffer from disturbed verbalization and legasthenia causing difficulties in communication and learning, many develop autism spectrum disorders. Neuro-imaging showed anomalies in the brain of KS patients. KS mice also exhibit cognition, memory, and learning difficulties and help to elucidate the psycho-neurological shortcomings.

Testosterone treatment

All KS men develop a lack of testosterone sooner or later. Although the capacity for biosynthesis of testosterone of the hyperplastic Leydig cells is normal, the hormone seems to be trapped in the testis due to impaired blood flow as shown in the KS mouse. Therefore, testosterone substitution remains the prime option in treating KS men. As current modalities of testosterone substitution cannot remedy all symptoms, recent discussion focuses on when the treatment should be initiated (prepubertal, pubertal, or adult?) and what the optimal serum levels should be.

Acknowledgements

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under HiCi grant no. (1434-141-453). The authors, therefore, acknowledge with thanks DSR technical and financial support.

O19 A new look to reproductive medicine in the era of genomics

Serdar Coskun

Assisted Reproductive Technology Laboratory, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, KSA

Recent advances in the molecular biology made the genomic technologies widely available to the medical community. Reproductive medicine is also adapting these changes into its practice. The impact is more profound in the field of preimplantation genetic diagnosis (PGD). The main limitation in PGD has been the availability of a small quantity of genetic material hampering the use of genomic technologies. In recent years, improved whole genome amplification techniques with more sensitive detection methods made possible to use microarrays and next generation sequencing in PGD. We now can identify single gene disorders in embryos along with screening all 23 chromosomal abnormalities. Currently, there are studies evaluating the effect of chromosomal screening in improving the in vitro fertilization outcomes. Another impact of genomic technologies will be on understanding the mechanism of infertility. There is about 20 % of the infertility cases considered as “unexplained” with no known causes according to the current tests available. Whole genome sequencing might help to uncover the genetic bases of these cases. We have recently shown TLE6 mutation the underlying cause of repeated fertilization failure. The third impact of these technologies will be on treatment where drugs and dose could be individualized according to the genetic background of a person. Some of the genomic technologies are also being used in prenatal diagnosis (PND) in the clinical settings. Namely, the noninvasive PND is now available to the patients as a routine test. In this presentation, the newly adapted genomic methodologies and their applications to the reproductive medicine will be reviewed.

P1 Wnt signalling receptors expression in Saudi breast cancer patients

Muhammad Abu-Elmagd1,2, Abdelbaset Buhmeida1,2, Ashraf Dallol1,2, Jaudah Al-Maghrabi3, Sahar Hakamy1, Wejdan Al-Qahtani1, Asia Al-Harbi1, Shireen Hussain1, Mourad Assidi1,2, Mohammed Al-Qahtani1,2, Adel Abuzenadah1,2

1Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; 2Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Pathology, Faculty of medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence: Muhammad Abu-Elmagd (mabuelmagd@kau.edu.sa) – Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Background

Wnt ligands and their receptors “Frizzleds’ constitute a pivotal signalling that mediates a considerable number of cellular events during development, in adulthood and cancer including fate determination, polarity, tissue patterning, and proliferation. At least ten members of frizzled transcription factors have been characterised each of which is known as seven transmembrane G protein-coupled receptor. In cancer, frizzled receptors expression is associated with tumour development and patient’s outcomes including recurrence and survival [1]. High level of Fizzled6 expression in particular was reported during leukemogenesis [2]. Our current study aimed to analyse the expression pattern of a number of frizzled receptors in Saudi Arabia breast cancer (BC) tissue and here we present only FRIZZLED6 (FZD6) analysis.

Subjects and methods

BC tissue samples from more than 615 patients aged between 25-80 years who were reported for BC complications at King Abdulaziz University Hospital, Jeddah, Saudi Arabia were used. All samples, processed for paraffin sectioning, were subjected to tissue array technology and automated immunohistochemistry staining for Frizzled genes according to the protocol described in detail in [3].

Results

Expression pattern analysis of Frizzled6 revealed that its expression is mainly cytoplasmic while few cases showed, in addition, nuclear expression reflecting the heterogeneity of the tumour. The majority of BC tissues (60 % of the samples) showed no/weak expression patterns while around 40 % of the samples showed moderate to high level of the expression.

Conclusions

We have analysed the expression pattern of a number of Wnt signalling receptors (Frizzleds) in Saudi BC patients. Among these receptors is FZD6 which revealed in general weak expression. FZD6 expression is currently further analysed and being correlated with patients clinico-pathological features in order to evaluate its prognostic significance in BC.

Acknowledgements

This project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH) – King Abdulaziz City for Science and Technology, Saudi Arabia – Award number (13-CIPM-01).

References

1. Ueno K, Hirata H, Hinoda Y, Dahiya R: Frizzled homolog proteins, microRNAs and Wnt signaling in cancer. International journal of cancer Journal international du cancer 2013, 132(8):1731-1740.

2. Wu QL, Zierold C, Ranheim EA: Dysregulation of Frizzled 6 is a critical component of B-cell leukemogenesis in a mouse model of chronic lymphocytic leukemia. Blood 2009, 113(13):3031-3039.

3. Al-Khattabi H, Kelany A, Buhmeida A, Al-Maghrabi J, Lari S, Chaudhary A, Gari M, Abuzenadah A, Al-Qahtani M: Evaluation of HER-2/neu gene amplification by fluorescence in situ hybridization and immunohistochemistry in Saudi female breast cancer. Anticancer research 2010, 30(10):4081-4088.

P2 Analysis of oxidative stress interactome during spermatogenesis: a systems biology approach to reproduction

Burak Ozkosem1, Rick DuBois2

1Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA; 2Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA

Correspondence: Burak Ozkosem (burak.ozkosem@mail.mcgill.ca) – Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA

Background

Daily production of spermatozoa is a complex process and severely affected by oxidative stress. Spermatogenesis is one of the most gainful cell-producing systems in animals, generating 100 million spermatozoa each day forming high levels of protein-protein interactions (PPIs). Interactions depend on cell type, cell cycle phase, developmental stage, oxidative stress conditions, redox mediated protein modifications, presence of cofactors, and other binding partners. To better understand how sperm production is regulated, we performed network analysis of redox mediated PPIs during spermatogenesis. Interactions between the major signaling pathways in germ cells yet to be investigated [1]. Furthermore, interactions between antioxidant defense proteins and sperm signaling pathways (e.g., energy production, sperm-egg recognition, and fertilization) are not known.

Results

Our interactome analysis combined experimental and predicted PPIs [2,3]. PPIs that were coming from different databases showed a small overlap, and also male infertility proteins are not well known and knowledge of their interactors are based on low throughput studies. Only 26 proteins were found to be annotated in the ReactomeDB [4]. Our curated network representing Antioxidant Response pathway proteins and their interactors consists of 101 nodes and 235 edges.

Conclusions

Almost 40 % of human genes do not have a PfamA or GO annotation, no current studies provide a list of potential functions [3,4]. We found that only two proteins, superoxide dismutase 1 and 2 (SOD1 and SOD2) had genetic interactions, while SOD3 had only one physical interaction which was inferred from mouse, also nitric oxidase 4 (NOX4) and glutathione peroxidase 5 (GPX5) didn’t show any interactions Other proteins showed physical interactions and more than 90 % those proteins had minimum 4 unique interactors. Oxidative stress response proteins with high number of interactions are involved in biological processes in sperm, and by manipulating this PPI network we simulated sperm specific conditions. Catalase (CAT) is not present in mature sperm, in the absence of CAT, the interactome would shift to new PPIs involving other antioxidants or alternative pathways. Combining computational and experimental tools for identifying PPIs will enrich the maps of PPIs in germ cells, and help understanding molecular basis of the increase in infertile population.

References

1. Ozkosem, B., & O'Flaherty, C: Detrimental Effects of Oxidative Stress on Spermatozoa Lacking Peroxiredoxin 6. Free Radic Biol and Med 2012, 53: S86.

2. Orchard S, Kerrien S, Abbani S, Aranda B, Bhate J, Bidwell S, Bridge A, Briganti L, Brinkman Fiona SL, Cesareni G, Chatr-aryamontri A, Chautard E, Chen C, Dumousseau M, Goll J, Hancock Robert EW, Hannick LI, Jurisica I, Khadake J, Lynn DJ, Mahadevan U, Perfetto L, Raghunath A, Ricard-Blum S, Roechert B, Salwinski L, Stümpflen V, Tyers M, Uetz P, Xenarios I, Hermjakob H: Protein interaction data curation: the International Molecular Exchange (IMEx) consortium. Nat Methods 2012, 9:345–350.

3. Barabási AL, Gulbahce N, Loscalzo J: Network medicine: a network-based approach to human disease. Nat Rev Genet 2011, 12: 56–68.

4. Vidal, M: Interactome Modelling. FEBS Letters 2005, 579, 8: 1834-1838
Fig. 1 (abstract P2)

Expression details of known male fertility related proteins and functional Interactions

Table 1 (abstract P2)

Major antioxidant response/defense proteins in testes and their interaction statistics

 

High Throughput

Low Throughput

Total Interactions

Unique Interactors

Publications

CAT

13 (50 %)

13 (50 %)

26

13

15

GPX1

1 (10 %)

9 (90 %)

10

4

3

GPX2

3 (100 %)

0 (0 %)

3

3

1

GPX3

0 (0 %)

1 (100 %)

1

1

1

GPX4

5 (100 %)

0 (0 %)

5

4

4

GPX5

0 (0 %)

0 (0 %)

0

0

0

GPX6

2 (100 %)

0 (0 %)

2

2

2

GPX7

2 (100 %)

0 (0 %)

2

2

2

NOS2

139 (79 %)

36 (21 %)

175

148

17

NOX4

0 (0 %)

0 (0 %)

0

0

0

NOX5

0 (0 %)

5 (100 %)

5

4

2

PRDX1

92 (78 %)

26 (22 %)

118

98

52

PRDX2

45 (75 %)

15 (25 %)

60

53

23

PRDX3

33 (73 %)

12 (27 %)

45

33

24

PRDX4

42 (78 %)

12 (22 %)

54

42

27

PRDX5

35 (100 %)

0 (0 %)

35

32

11

PRDX6

41 (75 %)

14 (25 %)

55

45

29

SOD1

18 (24 %)

58 (76 %)

76

44

31

SOD2

18 (78 %)

5 (22 %)

23

19

13

SOD3

0 (0 %)

1 (100 %)

1

1

1

SRXN1

35 (100 %)

0 (0 %)

35

35

2

TXN

52 (60 %)

35 (40 %)

87

61

39

P3 Interleukin-18 gene variants are strongly associated with idiopathic recurrent pregnancy loss

Safia S Messaoudi1, Maryam T Dandana2, Touhami Mahjoub2, Wassim Y Almawi3

1Forensic Biology Department, College of Forensic Sciences, Naif Arab University for Security Sciences, Riyadh, Kingdom of Saudi Arabia; 2College of Pharmacy of Monastir, Monastir, Tunisia; 3Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain

Correspondence: Safia S Messaoudi (safsafsophie@gmail.com) – Forensic Biology Department, College of Forensic Sciences, Naif Arab University for Security Sciences, Riyadh, Kingdom of Saudi Arabia

Background

Interleukin-18 (IL-18) is an important regulator of innate and acquired immune responses with a proposed role in a variety of early inflammatory responses [1]. This cytokine is actively involved in the regulation of immune responses in order to have a successful pregnancy and enhances either T helper 1 (Th1) or Th2 differentiation depending on the immunologic state [2]. Alterations of IL-18 expression and secretion were linked with the pathogenesis of pregnancy complications, such as recurrent pregnancy loss (RPL) [3].

Furthermore, genetic variants in IL-18 gene were identified to have an impact on the level of IL-18 protein secretion [4].

In this study, we investigate the possible associations of Interleukin-18 (IL-18) promoter single nucleotide polymorphisms (SNPs) with idiopathic recurrent pregnancy loss (RPL).

Materials and methods

We evaluated −656C/A (rs1946519), −137G/C (rs187238), −119A/C (rs360718), and −105G/A (rs360717) IL-18 promoter polymorphisms (SNPs) by Taqman assays in 470 Tunisian women comprising 235 RPL cases and 235 age-matched multiparous control women. The association of IL-18 alleles, and genotypes with RPL was evaluated by Fisher’s exact test and regression analysis. A value of P < 0.05 will be considered statistically significant.

Results

Genotype distribution of −656C/A, −137G/C, −119A/C, and −105G/A was in Hardy–Weinberg equilibrium. The A allele of −105G/A (P < 0.001) and the A allele of −656C/A (P < 0.01), but not the C allele of −119A/C (P = 0.93) or C allele of −137G/C (P = 0.32), were significantly associated with RPL. Significant differences in −656C/A (P < 0.001) and −105G/A (P < 0.001), but not −119A/C (P = 0.78) or −137G/C (P = 0.12) regarding the distribution of genotypes were noted between RPL cases and control women. Since both variants were linked with reduced IL-18 availability [4] our findings underscore the significance of reduced IL-18 in the maintenance of normal pregnancy [5], and in the pathogenesis of pregnancy complications [6], including RPL [4]. Our results confirm the lack of association between rs187238and RPL in southern Iranian women [7].

Conclusions

We demonstrated that the IL-18 promoter variants −656C/A and −105G/A are significantly associated with RPL among Tunisian women.

References

1. Dinarello CA, Novick D, Kim S, Kaplanski G. Interleukin-18 and IL-18 binding protein. Front Immunol. 2013 Oct 8;4:289.

2. Chaouat, G., Ledee-Bataille, N., Dubanchet, S., Zourbas, S., Sandra, O., Martal, J., 2004. TH1/TH2 paradigm in pregnancy: paradigm lost? Cytokines in pregnancy/early abortion: reexamining the TH1/TH2 paradigm. Int. Arch. Allergy Immunol. 134, 93–119.

3. Ostojić, S., Volk, M., Medica, I., Kapović, M., Meden-Vrtovec, H., Peterlin, B., 2007. Polymorphisms in the interleukin-12/18 genes and recurrent spontaneous abortion. Am. J. Reprod. Immunol. 58, 403–408.

4. Barbaux, S., Poirier, O., Godefroy, T., Kleinert, H., Blankenberg, S., Cambien, F., Tiret, L., 2007. Differential haplotypic expression of the interleukin-18 gene . Eur. J. Hum. Genet. 15, 856–863.

5. Wilson, R., Moor, J., Jenkins, C., Miller, H., Walker, J.J., McLean, M.A., et al., 2004. Abnormal first trimester serum interleukin 18 levels are asso-ciated with a poor outcome in women with a history of recurrent miscarriage. Am. J. Reprod. Immunol. 51, 156–159.

6. Roland, L., Gagné, A., Bélanger, M.C., Boutet, M., Julien, P., Bilodeau, J.F., 2010. Plasma interleukin-18 (IL-18) levels are correlated with antioxidant vitamin coenzyme Q(10) in preeclampsia. Acta Obstet. Gynecol. Scand. 89, 360–366.

7. Naeimi, S., Ghiam, A.F., Mojtahedi, Z., Dehaghani, A.S., Amani, D., Ghaderi, A., 2006. Interleukin-18 gene promoter polymorphisms and recurrent spontaneous abortion. Eur. J. Obstet. Gynecol. Reprod. Biol. 128, 5–9.
Table 2 (abstract P3)

IL-18 SNPs analyzed

Name

HWE P

Minor allele

Cases MAFa

Controls MAF

P b

OR (95% CI)

rs1946519

0.58

A

0.46

0.31

<0.001

1.91 (1.48–2.45)

rs187238

0.65

A

0.31

0.28

0.32

1.15 (0.89–1.50)

rs360718

0.45

C

0.27

0.27

0.93

0.98 (0.75–1.28)

rs360717

0.12

A

0.49

0.30

<0.001

2.18 (1.70–2.78)

MAF, minor allele frequency; HWE, Hardy–Weinberg equilibrium

aMinor allele defined based on control frequency

bObserved P value

Table 3 (abstract P3)

IL-18 genotype frequencies

SNP

Genotype

Casesa

Controlsa

P b

OR (95% CI)

rs1946519

C/C

66 (0.28)c

114 (0.48)

<0.001

1.00 (reference)

 

C/A

120 (0.51)

97 (0.41)

 

2.11 (1.42–3.15)

 

A/A

49 (0.21)

24 (0.10)

 

3.19 (1.82–5.60)

rs187238

G/G

122 (0.52)

126 (0.53)

0.12

1.00 (reference)

 

G/C

82 (0.35)

92 (0.39)

 

0.86 (0.59–1.25)

 

C/C

31 (0.13)

19 (0.08)

 

1.61 (0.90–2.90)

rs360718

A/A

132 (0.56)

127 (0.54)

0.61

1.00 (reference)

 

A/C

82 (0.35)

89 (0.38)

 

0.84 (0.58–1.22)

 

C/C

21 (0.09)

19 (0.08)

 

1.05 (0.56–1.96)

rs360717

G/G

82 (0.35)c

120 (0.51)

<0.001

1.00 (reference)

 

G/A

78 (0.33)

89 (0.38)

 

1.22 (0.83–1.80)

 

A/A

75 (0.32)

26 (0.11)

 

4.08 (2.51–6.64)

aA total of 235 RPL cases and 235 control subjects were included

bPearson’s chi squared test

cNumber of subjects (frequency)

P4 Effect of environmental factors on gene-gene and gene-environment reactions: model and theoretical study applied to environmental interventions using genotype

S. Abdalla1, M. Nabil Al-Aama2

1Department of Physics, Faculty of Science, King Abdulaziz University Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia; 2Internal Medicine and Cardiology, King Abdulaziz University Medical School, Jeddah, Saudi Arabia

Correspondence: S. Abdalla (smabdullah@kau.edu.sa) – Department of Physics, Faculty of Science, King Abdulaziz University Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia

Background

Genotype is affected by both the ecological [1, 2] and genetic factors [3] to some known and conjoint diseases of contrast where the size of which genes and environment interact. Neglecting the presence of risk factors, ecological factors will lead to assess the probabilities of some benefits in a definite population sample. Here, there must be a general methodology for the analysis of twin data as the gene interactions (epistasis), the possible weightiness of the gene, and genetic interactions of the environment, and the conditions which stop the presumption of “equal environments” for mono monozygotic and dizygotic twins.

Materials and methods

A model to study the genes and gene to gene environment interactions [1, 2] is presented. The classic twin study assumptions, including Fisher’s hypothesis which presumes that genes act as hazard points for combined features in a style needs dominate polygenic added: long way. Provided there will be no confusion when applying: Environmental-, twin- and family- data; results show an issue for every trait or common disease [4]. Every fine-detail that is present through the solution space will match with a different system of the potential hazard and the action of environment and genes. Every fine-detail that is present through the solution space will match with a different system of the potential hazard and the action of environment- [5] and genes [6].

Conclusions

The present data showed the possibility of limiting the spread of conjoint diseases when applying environmental-interactions to certain gene. Our results emphasize the significance of the genetic makeup of the individual when estimating the possible hazards of complex diseases is overstated [3, 4]. Moreover, when the phenomena are a powerful, genetically, because of epistasis, environmental explanation for the large risk of common brotherhood is reasonable, even when considering high heritage typical cases. Thus, the results confirm the potential the previously rejected on the light of the data of the case twin. Thus, genetic models of family assembly may be incorrect and chase additional genes can be counter-productive to a large extent.

References

1. Abdalla S, Al-Hadeethi Y., Gene’s alternations with exposure time of environmental factors, Gene. 2013 Oct 10; 528(2):256-60. doi:10.1016/j.gene.2013.06.065. Epub 2013 Jul 13.

2. Abdalla S, Al-Hadeethi Y and El-Shewy E K, Effect of environmental factors on gene alterations in complex diseases: simulation study using Gene-Environment iNteraction Simulator 2, BMC Genomics 2014, 15(Suppl. 2):P47 doi:10.1186/1471-2164-15-S2-P47

3. Abdalla S, M Letarte, Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease, J Med Genet. 2006 February; 43(2): 97–110. doi:10.1136/jmg.2005.030833, PMCID: PMC2603035

4. Veronique MM Vorselaars, Sebastiaan Velthuis, Repke J Snijder, Jan Albert Vos, Johannes J Mager, Martijn C Post, Pulmonary hypertension in hereditary haemorrhagic telangiectasia, World J Cardiol. 2015 May 26; 7(5): 230–237. Published online 2015 May 26. doi:10.4330/wjc.v7.i5.230, PMCID: PMC4438464

5. Ferdos Alaa el Din, Sylvie Patri, Vincent Thoreau, Montserrat Rodriguez-Ballesteros, Eva Hamade, Sabine Bailly, Brigitte Gilbert-Dussardier, Raghida Abou Merhi, Alain Kitzis, Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by Hereditary Hemorrhagic Telangiectasia, PMCID: PMC4503601

6. Abdalla S, Cymerman U, Rushlow D, Chen N, Stoeber GP, Lemire EG, Letarte M., Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia, Hum Mutat. 2005 Mar;25(3):320-1.

P5 Genomics and transcriptomic analysis of imatinib resistance in gastrointestinal stromal tumor

Asmaa Elzawahry1, Tsuyoshi Takahashi2, Sachiyo Mimaki3, Eisaku Furukawa1, Rie Nakatsuka2, Isao Kurosaka1, Takahiko Nishigaki2, Hiromi Nakamura4, Satoshi Serada4, Tetsuji Naka5, Seiichi Hirota6, Tatsuhiro Shibata5, Katsuya Tsuchihara3, Toshirou Nishida7, Mamoru Kato1

1Department of Bioinformatics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuuoo-ku, Tokyo 104-0045, Japan; 2Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita City, Osaka, 565-0871, Japan; 3Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan;