As little is known about the blood profile of camels in Libya, this article is the first of a 4-part series describing the biochemical and haematological blood profile in Libyan camels. Part 1 of these manuscripts determines the values of enzymes, metabolites, electrolytes and haematological indices in the blood of Libyan camels, parts 2-4 evaluates the effects of breed, gender and age respectively on these values. In this study, blood samples were collected from sixty six camels of three different breeds, different ages and with both sex. The blood of the studied camels showed (i) average values of Potassium (K), Calcium (Ca), Magnesium (Mg), Phosphorus (Ph), Haemoglobin (Hb), Packed Cell Volume (PCV) and White Blood Cell (WBC) counts (ii) low values of Sodium (Na), Iron (Fe), total proteins, albumin, globulin, creatinine, cholesterol, triglycerides, Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), and low serum activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and amylase (AMS) enzymes and (iii) high values of glucose, urea, Red Blood Cell (RBC) counts, Erythrocyte Sedimentation Rate (ESR) and Mean Corpuscular Haemoglobin Concentration (MCHC). The finding of this study was documented and compared with the findings of similar studies performed elsewhere. arabic 25 English 134
Anwar Mustafa Abdalhadi Abdalmula, Amal Omar Elarif Buker, Fathia mahmoud Mohammad Ashour, Mansur Ennuri Moftah Shmela, , Ismail M Abograra, , Fahima A Alnagar(8-2018)

The human 11p15 region is divided into two independent imprinted domains, the H19/IGF2 and CDKN1C/KCNQ1 domains. Each domain is regulated by its own imprinting control regions, ICR1 and ICR2, which carry opposite germline imprints. The expression of 11p15 imprinted genes is regulated by two major mechanisms. ICR1 binds a zinc finger protein (CTCF) on the unmethylated maternal allele and acts as a chromatin insulator, whereas ICR2 is unmethylated on the paternal allele and serves as a promoter for a regulatory non-coding RNA (KCNQ1OT1). Dysregulation of 11p15 genomic imprinting results in two human foetal growth disorders: the Beckwith-Wiedemann (BWS) and the Silver-Russell (SRS) syndromes, which display opposite growth phenotypes. Various 11p15 epigenetic and genetic defects result in BWS and SRS. Gain or loss of DNA methylation account for 60% of BWS and SRS and, in most cases, the mechanism of the DNA methylation defect is unknown. The overall aim of this thesis was to decipher the mechanisms resulting in loss or gain of DNA methylation at ICR1 or ICR2 by investigating large cohorts of BWS and SRS patients displaying a “primary” DNA methylation defect. We aimed at establishing what was the incidence of copy number variations (CNVs) (duplications, deletions and segmental uniparental isodisomies) confined to one or one part of the H19/IGF2 or CDKN1C/KCNQ1 domains. We also screened extensively the ICR1 imprinting control region in BWS and SRS patients to identify new genetic defects. We show in this work that genetic defects in cis account for a significant proportion (approximately 30%) of BWS patients with ICR1 gain of DNA methylation but are rare in SRS and BWS patients with loss of DNA methylation at ICR1 and ICR2, respectively. We describe novel small gain and loss CNVs involving only part of the two domains in BWS and SRS. We also describe, for the first time, mutations and small deletions involving binding sites for the OCT4 and SOX2 pluripotency factors. Those defects account for approximately 14% of BWS cases and result in a BWS phenotype upon maternal transmission. We further characterize the role of OCT4/SOX2 pluripotency factors in the maintenance of genomic imprinting at the H19/IGF2 domain in mouse embryonic stem cells. By screening the whole 11p15 region for susceptibility alleles for loss or gain of DNA methylation, our group identified a novel 4.5 kb cis-regulatory region within the CDKN1C/KCNQ1 domain. A specific 4.5 kb haplotype confers, upon maternal transmission, a risk of ICR2 loss of DNA methylation in BWS patients. This study investigated the mechanism involved in the risk of ICR2 loss of DNA methylation in BWS and showed that within this 4.5 kb region, two SNPs (rs11823023 and rs179436) affect CTCF occupancy at DNA motifs flanking the CTCF 20 bp core motifs. This study identifies a new cis-regulatory region and highlights the crucial role of CTCF for the regulation of genomic imprinting at the CDKN1C/KCNQ1 domain. These recent findings bring new insights in the regulation of genomic imprinting at both the IGF2/H19 and CDKN1C/KCNQ1 domains. arabic 8 English 50
Mansur Ennuri Moftah Shmela(9-2014)

The imprinted expression of the IGF2 and H19 genes is controlled by the imprinting control region 1 (ICR1) located at chromosome 11p15.5. DNA methylation defects involving ICR1 result in two growth disorders with opposite phenotypes: an overgrowth disorder, the Beckwith-Wiedemann syndrome (maternal ICR1 hypermethylation in 10% of BWS cases) and a growth retardation disorder, the Silver-Russell syndrome (paternal ICR1 loss of methylation in 60% of SRS cases). In familial BWS, hypermethylation of ICR1 has been found in association with microdeletion of repetitive DNA motifs within ICR1 that bind the zinc finger protein CTCF; but more recently, ICR1 point mutations were described in BWS pedigrees. We present a case report of two brothers with BWS and prolonged post-pubertal growth resulting in very large stature. A maternally inherited point mutation was identified in ICR1 in both brothers, which altered binding of OCT transcription factors. The same mutation was present on the paternally inherited allele of their unaffected mother. This is a second report of a point mutation causing ICR1 hypermethylation by altering an OCT-binding motif. The atypical growth phenotype of the brothers may be connected to the unusual underlying cause of their BWS. arabic 24 English 118
Rebecca L Poole, Donald J Leith, Louise E Docherty, Mansur Ennuri Moftah Shmela, Christine Gicquel,, Miranda Splitt, I Karen Temple, Deborah J G Mackay(2-2012)