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)

Salmonella enterica can be considered as one of the most important causes of foodpoisoning with poultry thought to be the main source. Although S. Typhimurium, S. Enteritidis and the vast majority of other Salmonella serovars generally produce little systemic disease in adult chickens, they are able to colonize the alimentary tract of poultry. The two caeca are the main sites of the colonization of Salmonellae in chickens, and the bacteria can be easily harvested from the caeca for analysis. Bacterial proteins analysed utilizing SDS-PAGE showed differences between in vitro and in vivo that out of about 40 protein bands of in vitro preparation only a few (3-5) bands can be visualized from in vivo preparations. We suggested that some avian proteases might be responsible. Accordingly, and to investigate the hypothesis that bacterial-precipitated protein harvested from chickens is thought to be more protective than bacteria grown in broth culture, the immunogenicity of protein-precipitated vaccines harvested from chicken intestine and those from broth culture (in vitro), were compared using bacterial proteins as an orally inoculated vaccine candidate in chicken. The results demonstrated that the in vitro sonicated proteins obtained from a nutrient broth culture had a much better protective vaccine effect than the in vivo sonicated proteins preparations harvested from bacteria grown in chickens arabic 14 English 81
Altayeb Elazomi, Elhadi Araibi, Abdulgader Dhawi, Hatem Khpiza, Susan Liddell, Margret Lovell, Paul Barrow(12-2016)

Peste des Petits Ruminants (PPR) is considered one of the most important transboundary animal diseases (TADs) with socio-economic impacts on national and international levels. During 2015-2016 a total of 690 serum samples were collected from unvaccinated domestic ruminants of which 555 sheep, and 135 goats representing teen provinces distributed in four Libyan branches (Green Mountain, Benghazi, West Mountain and Sabha). The sample were analysed at IZSAM, Teramo, Italy, by using competitive ELISA, IDvet innovative diagnostics (IDvet, 310 rue Louis Pasteur-34790 Grabels, France). The overall sero-prevalence rate (SPR) of PPR antibodies was estimated to be 41% (95% CL: 36% to 46%) among sheep and 39% (95% CL: 28% to 45%) among goat. A chi-square test was used to evaluate the probability of differences observed among SPR of infection. The results showed that the SPR of PPR was significantly (P= 0.015) higher in adult animals 41% (95% CL= 37%-46%) than in the young 24% (95% CL= 17%- 32%). The highest SPR 75% (95% CL= 61%-85%) was recorded in Sabha province (Southern Libya) which highlighted statistically difference (P= 0.00001). The preliminary results of the present study could be useful to better focus on specific area of Libya to improve understand and evaluate the risk factors for disease spreading and to plan disease control activities as requested by FAO/OIE (PPR Global Control and Eradication Strategy). arabic 19 English 100
Abdusalam Sharef Abdusalam Mahmoud(1-2020)