Background Disruption of 11p15 imprinting results in two fetal growth disorders with opposite phenotypes: the Beckwith–Wiedemann (BWS; MIM 130650) and the Silver–Russell (SRS; MIM 180860) syndromes. DNA methylation defects account for 60% of BWS and SRS cases and, in most cases, occur without any identified mutation in a cis-acting regulatory sequence or a trans-acting factor. Methods We investigated whether 11p15 cis-acting sequence variants account for primary DNA methylation defects in patients with SRS and BWS with loss of DNA methylation at ICR1 and ICR2, respectively. Results We identified a 4.5 kb haplotype that, upon maternal transmission, is associated with a risk of ICR2 loss of DNA methylation in patients with BWS. This novel region is located within the second intron of the KCNQ1 gene, 170 kb upstream of the ICR2 imprinting centre and encompasses two CTCF binding sites. We showed that, within the 4.5 kb region, two SNPs (rs11823023 and rs179436) affect CTCF occupancy at DNA motifs flanking the CTCF 20 bp core motif. Conclusions This study shows that genetic variants confer a risk of DNA methylation defect with a parent-of-origin effect and highlights the crucial role of CTCF for the regulation of genomic imprinting of the CDKN1C/KCNQ1 domain. arabic 26 English 132
Julie Demars, Mansur Ennuri Moftah Shmela, Abdul Waheed Khan , Kai Syin Lee, Salah Azzi, Patrice Dehais, Irène Netchine, Sylvie Rossignol, Yves Le Bouc, Assam El-Osta, Christine Gicquel(7-2014)

Abstract As little is known about the blood profile of camels in libya, this article is the second of a 4-part series describing the biochemical and haematological blood profile in Libyan camels. In Part 1 of these manuscripts, the overall blood biochemical and haematological mean values of camels in Libya were determined, parts 2-4 evaluates the effects of breed, gender and age respectively on these values. Blood samples were collected from three camel breeds, namely, Fakhreya, Sirtaweya and Mahari, and the levels of enzymes, metabolites, electrolytes and haematological indices were measured. The blood of the Sirtaweya breed showed (i) higher levels of aspartate aminotransferase (AST), albumin and Phosphorus (Ph), than the other two breeds, (ii) higher levels of lactate dehydrogenase (LDH), amylase (AMS) and total proteins than the Fakhreya breed and (iii) higher levels of glucose, triglycerides, total cholesterol, Very Low Density Lipoprotein (VLDL), Low Density Lipoprotein (LDL), Calcium (Ca), Packed Cell volume (PCV), Mean Corpuscular Volume (MCV) and Albumin/Globulin (A/G) ratio than the Mahari breed. The Fakhreya breed had (i) higher levels of urea, Iron (Fe), Haemoglobin (Hb), Mean Corpuscular Haemoglobin (MCH) and neutrophils number than the other two breeds, (ii) higher levels of glucose, A/G, LDL, Ca, PCV, MCV and monocytes number than the Mahari breed and (iii) higher levels of erythrocyte osmotic fragility, MCH and Mean Corpuscular Hemoglobin Concentration (MCHC) than the Sirtaweya breed. The Mahari breed had (i) higher levels of globulin than the other two breeds, (ii) higher levels of AMS than the Fakhreya breed and (iii) higher levels of erythrocyte osmotic fragility, Erythrocyte Sedimentation Rate (ESR), MCHC than the Sirtaweya breed. The tested blood parameters in the three Libyan breeds in this study were affected by breed variations. arabic 28 English 143
Anwar Mustafa Abdalhadi Abdalmula, F. A. Alnagar, Amal Omar Elarif Buker, Fathia mahmoud Mohammad Ashour, I. M. Abograra , Mansur Ennuri Moftah Shmela(10-2018)

The imprinted 11p15 region is organized in two domains, each of them under the control of its own imprinting control region (ICR1 for the IGF2/H19 domain and ICR2 for the KCNQ1OT1/CDKN1C domain). Disruption of 11p15 imprinting results in two fetal growth disorders with opposite phenotypes: the Beckwith-Wiedemann (BWS) and the Silver-Russell (SRS) syndromes. Various 11p15 genetic and epigenetic defects have been demonstrated in BWS and SRS. Among them, isolated DNA methylation defects account for approximately 60% of patients. To investigate whether cryptic copy number variations (CNVs) involving only part of one of the two imprinted domains account for 11p15 isolated DNA methylation defects, we designed a single nucleotide polymorphism array covering the whole 11p15 imprinted region and genotyped 185 SRS or BWS cases with loss or gain of DNA methylation at either ICR1 or ICR2. We describe herein novel small gain and loss CNVs in six BWS or SRS patients, including maternally inherited cis-duplications involving only part of one of the two imprinted domains. We also show that ICR2 deletions do not account for BWS with ICR2 loss of methylation and that uniparental isodisomy involving only one of the two imprinted domains is not a mechanism for SRS or BWS. arabic 22 English 137
- Demars, J., S. Rossignol, I. Netchine, K. S. Lee, Mansur Ennuri Moftah Shmela, L. Faivre, J. Weill, S. Odent, S. Azzi, P. Callier, J. Lucas, C. Dubourg, J. Andrieux, Y. Le Bouc, A. El-Osta , C. Gicquel(10-2011)