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-Q...

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Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. Methods: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. Results: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. Conclusion: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met.

Background: The type 3 Von Willebrand International RegistrieSInhibitor Prospective Study (3WINTERS-IPS) is a no-profit, investigator initiated, multicenter, European-Iranian observational, retrospective and prospective study on patients with diagnosis of type 3 VWD. Patients with type 3 von Willebrand Disease (VWD3) have markedly reduced levels of von Willebrand factor (VWF) and very severe bleeding phenotype. Due to the recessive inheritance pattern, VWD3 is by definition a rare bleeding disorder (1:Million) but its prevalence may increase in countries like Iran with consanguineous marriages. Aim: To identify the VWF genetic defects in a cohort of European and Iranian patients with previously diagnosed VWD3 enrolled into the 3WINTERS-IPS project. Methods: Patients classified locally as VWD3 were enrolled in the study following informed consent. 141 patients were from 9 different European countries and 119 patients were from the Islamic Republic of Iran. Plasma/buffy-coat samples were sent to expert labs to confirm patient's laboratory phenotype and to perform molecular analysis. PCR and Sanger sequencing/ next generation sequencing and multiplex-ligation dependent probe amplification were used in Hamburg, Sheffield and Milan to confirm previously identified variants or to seek previously unidentified variants. Results: DNA samples from 122 patients from Europe and 114 patients from Iran were analyzed at the molecular level. Of the 236 VWD3 patients under evaluation 24 are still in progress. Of the 212 fully evaluated patients 139 were homozygous (EU/IR=46/93) and 43 were compound heterozygous (EU/IR=36/7). In the remaining 30 patients no variants were identified in 19 samples (EU/IR=6/13) and only one variant was found in the remaining 11 cases (EU/IR=10/1). 135 (EU/IR=82/53) different gene defects were identified among the 375 (EU/IR=174/201) alleles found in this study. Of these 135 variants identified 51(EU/IR=22/29) were not reported on the www.ensembl.org database. The distribution of the different type of variants identified in the two populations is shown in the Figure. The two charts are showing quite similar percentages of the variants identified, with a main exception for the Small deletions and Small insertions. Only five variants are shared among the two populations. Three of these are the "hotspot" variants at the Arg codon, p.Arg1659* (EU/IR=9/8), p.Arg1853* (EU/IR=2/3) and p.Arg2535* (EU/IR=1/2). However, a missense variant , p.Cys275Ser (EU/IR=1/2) and a large deletion, delEx1_Ex5 (EU/IR=1/2) were also found in both populations. Fifteen variants were recurrent and were found in 154 alleles, whereas 49 variants were found only once in the heterozygous state (EU/IR=40/9) and 50 variants were found only twice, mainly in the homozygous state (EU/IR=25/25). Six large deletions were identified (delEx1_Ex3, delEx1_Ex5, delEx14_Ex15, delEx17, delEx35_Ex52 and delEx1_Ex52) and a duplication (dupEx1_Ex28), nevertheless 52 alleles with missense variants were identified (EU/IR=20/32). Discussion: As expected, the majority of the Iranian patients were found to be homozygous (Homozygous/Compound Heterozygous=93/7) reflecting a high rate of consanguinity, nevertheless half of the European patients were found to be homozygous (Homozygous/Compound Heterozygous=46/36). The European populations demonstrated a higher heterogeneity of variants with 82 different variants among the 175 mutated alleles vs 53 different variants among the 201 mutated alleles identified in the Iranian population. Nevertheless, a higher number of previously unreported variants was found in the Iranian population (29) vs the European one (22), probably due to bias of previous investigations performed in European patients. Figure Figure. Disclosures Peyvandi: Ablynx: Other: Member of Advisory Board, Speakers Bureau; Shire: Speakers Bureau; Roche: Speakers Bureau; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Novo Nordisk: Speakers Bureau; Sobi: Speakers Bureau; Sobi: Speakers Bureau; Novo Nordisk: Speakers Bureau; Kedrion: Consultancy; Novo Nordisk: Speakers Bureau; Octapharma US: Honoraria; Novo Nordisk: Speakers Bureau; Sobi: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Kedrion: Consultancy; Novo Nordisk: Speakers Bureau; Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Octapharma US: Honoraria; Shire: Speakers Bureau; Roche: Speakers Bureau; Kedrion: Consultancy; Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Octapharma US: Honoraria; Octapharma US: Honoraria; Sobi: Speakers Bureau; Roche: Speakers Bureau; Octapharma US: Honoraria; Shire: Speakers Bureau; Sobi: Speakers Bureau; Roche: Speakers Bureau; Roche: Speakers Bureau; Shire: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Shire: Speakers Bureau. Schneppenheim:CSL Behring: Consultancy; SHIRE: Consultancy. Berntorp:Octapharma: Consultancy; CSL Behring: Consultancy; Shire: Consultancy, Other: honoraria for lecturing . Eikenboom:CSL: Research Funding. Mannucci:Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kedrion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Grifols: Speakers Bureau; Alexion: Speakers Bureau; Baxalta/Shire: Speakers Bureau; Novo Nordisk: Speakers Bureau. Mazzucconi:Baxalta-Shire: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novartis,: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau. Oldenburg:Swedish Orphan Biovitrum: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.