Nadhira Saidi-Mehtar’s research while affiliated with Université des Sciences et de la Technologie d'Oran Mohamed Boudiaf and other places

Retinoblastoma (RB) is an intraocular malignant tumour which occurs in children during the first months of life, with an incidence of 1 in 15,000 live births. Antioncogene RB1 located on chromosome 13q14.2, is at the origin of this pathology. For retinoblastoma development, two allele mutations of this gene are required. The aim of this study firstly, was to identify mutations that affect the RB1 gene in constitutional level, to detect early subject at risk or asymptomatic carriers and secondly to contribute on the understanding of the molecular pathogenesis. The study concerned 61 patients with retinoblastoma in Western Algeria. DNA from blood was used for amplification and gene sequencing. The results were completed by in-silico analysis using bio-informatic methods to know the mutation impact on the pRB1 protein function. Amplification and sequencing results gave nineteen different variations bases, including eight exonic changes: three missense mutations and five nonsense mutations located in exons 1,7,8,12,18,19,20 and 23. There are an important number of mutations located in twelve RB1 gene introns. These mutations were identified in germinal level for children with no family history of the disease. In conclusion, this study reported two new RB1 mutations in exons 1 and 7 among the eight identified. The mutations described in sporadic forms of retinoblastoma are transmissible forms in 13.11% of cases in our studied population. This study would improve role of genetic testing for management and family screening.

The local cattle populations belonging to the ‘Brune de l’Atlas’ cattle in Algeria and Morocco are potential resources in terms of genetic diversity and socioeconomic prevalence and their characterization is an essential step in any program designed to conserve genetic diversity. Our objectives were to assess the genetic diversity, the population structure and relationships among four Algerian cattle breeds, the Biskra, Cheurfa, Chelifienne and Guelmoise and of two Moroccan, the Oulmès-Zaër and Tidili by genotyping 50 309 single nucleotide polymorphism in 203 unrelated animals. A low population structure was observed across breeds with pairwise FST values ranging from 0.008 to 0.043, suggesting a high level of gene flow. These data were combined with the available data on cattle populations representative of Europe (EUT), West African taurine (WAT) and zebu (ZEB). Principle Components Analysis was carried out which revealed that the Maghrebin populations are closer to the EUT/ZEB population than to the WAT. Structure analysis confirmed this mixed origin of the Maghrebin cattle populations. We also detected the influence of zebu breeds in Cheurfa and Guelmoise populations. This study provides the first information about genetic diversity within and between Algerian and Moroccan cattle populations and gives a detailed description of their genetic structure and relationships according to their historical origins. This study revealed that several combined effects contributed to shape the genetic diversity of the six Maghrebin populations studied: (i) gene flow among local breeds, (ii) the recent introgression of European breeds in local Algerian breeds and (iii) the traditional management systems. The results of this study will primarily assist policy makers and livestock keepers to make useful decisions for improvement of genetic resources while ensuring the preservation and conservation of local breeds in Algeria and Morocco.

Basal cell carcinoma (BCC) is the commonest skin cancer in human. It is characterized by a strictly local malignity with a frequent tendency to relapse. BCC development results from the interaction between environmental factors and genetic alterations, including mutations in the TP53 gene involved in its progression and relapse. TP53 gene is named “guardian of the genome”, as it plays major roles in genomic stability. In addition to mutations, several polymorphisms had been detected in the wild-type TP53. The polymorphic variant is usually associated to BCC diseases at codon 72 of TP53 (Arg72Pro). Objectives: In the present study, we undertook a case control study to explore a possible association between TP53 Arg72Pro polymorphism and the predisposition to BCC in Northwest Algerian population. Methods: TP53 Arg72Pro polymorphism was investigated by PCR/RFLP then confirmed by DNA sequencing of 61 controls versus 50 BCC cases. Results: This study allows us to characterize BCC subgroups regarding age, tumor location, and relapse. No correlation was found between any of these criteria and each of the two variants of TP53 Arg72Pro. No association was found between TP53 Arg72Pro variants and developing BCC either (BCC group: Pro = 54%, versus Control group: Pro = 53 %, P > 0.05, OR 1.52 (0.89 - 2.60)). Finally, as expected, sun-exposure was confirmed as a risk factor for BCC. Conclusions: This study supports that analyzing TP53 Arg72Pro polymorphism is of no interest for identifying high-risk subjects for BCC in the Algerian population. Further studies are needed to explain the role of this polymorphism in genetic predisposition to BCC in some other populations. Keywords: Basal Cell Carcinoma; TP53; Arg72Pro Polymorphism; Genetic predisposition; Algerian population

Introduction - Le gène TP53 a fait l’objet de très nombreux travaux. Sa nature polymorphe et son rôle central dans la régulation du cycle cellulaire ont mis en évidence son potentiel de gène candidat dans la susceptibilité et la survenue de différents cancers. Bien que plusieurs polymorphismes du gène TP53 aient été étudiés comme facteurs de risque pour différents cancers, le plus largement étudié est le polymorphisme Arg72Pro (rs1042522), à l’origine d’une substitution d’une Arginie (Arg) en Proline (Pro) ou inversement, connu pour ses différentes fonctions biologiques.Notre objectif est d’explorer la participation du polymorphisme (SNP) Arg72Pro du gène TP53, dans l’expressivité du cancer colorectal (CCR) et du carcinome basocellulaire (CBC) dans une population de l’Ouest Algérien.Matériels et Méthodes - Le déséquilibre de transmission allélique de ce SNP a été réalisé sur une population constituée de 116 individus atteints de CCR, 50 sujets atteints de CBC et enfin une population contrôle constituée de 121 individus sains,par la technique de Biologie Moléculaire PCR/RFLP (Polymerase Chain Reaction/Restriction Fragment LengthPolymorphism).Résultats - L’association du marqueur Arg72Pro avec le CBC a montré une augmentation significative de l’allèle Pro chez les cas par rapport aux contrôles (54% vs 46%, OR=8,85 [4,98-16,03], p<10-7). Cet allèle semble conférer un risque important dedévelopper le CBC. Par ailleurs, les résultats n’ont montré aucune différence significative entre les sujets atteints de CCR et les contrôles, ce qui pourrait exclure son implication dans la survenue du CCR dans notre population (p>0.05).Conclusion - Le polymorphisme Arg72Pro du gène TP53 peut être considéré comme marqueur de risque pour le CBC mais pas pour le CCR.

Microsatellite information. (DOC)

Plot of the DeltaK statistics (Evanno et al., 2005) for the total sample. (DOCX)

Neighbor-net network constructed using the distance of Reynolds et al. (1983) considering the whole dataset arranged into three Algerian (light blue area) and three Egyptian (light yellow area) populations. (DOCX)

Pair-wise FST values among the three Egyptian (Falahy, Maghraby, Sudany) and the three Algerian (Azawad, Rguibi, Targui) populations. (DOCX)

Neighbor-joining tree constructed using the distance of Nei (1983) considering the whole dataset arranged into three Algerian and three Egyptian populations. (DOCX)

Neighbor-joining tree constructed using the distance of Reynolds et al. (1983) considering the whole dataset arranged into three Algerian and three Egyptian populations. (DOCX)