Genetics and Molecular Pathology Laboratory

Casablanca, Morocco

Genetics and Molecular Pathology Laboratory

Casablanca, Morocco
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Lakehayli S.,Laboratory of Pharmacology | Said N.,Laboratory of Pharmacology | El Khachibi M.,Genetics and Molecular Pathology Laboratory | El Ouahli M.,Sultan Moulay Slimane University | And 3 more authors.
Neuroscience | Year: 2016

Early-life events have long-term effects on brain structures and cause behavioral alterations that persist into adulthood. The present experiments were designed to investigate the effects of prenatal stress on diazepam-induced withdrawal syndrome and serotonin-1A (5HT1A) receptor expression in the raphe nuclei of adult offspring.The results of the present study reveal that maternal exposure to chronic footshock stress increased the anxiety-like behavior in the prenatally stressed (PS) animals withdrawn from chronic diazepam (2.5 mg/kg/day i.p for 1 week). Moreover, prenatal stress induced a down-regulation of 5HT1A mRNA in the raphe nuclei of adult offspring. To our knowledge, this study is the first to demonstrate that maternal exposure to chronic footshock stress enhances diazepam withdrawal symptoms and alters 5HT1A receptor gene expression in the raphe nuclei of adult offspring. Thus, more studies are needed to clarify the mechanisms underlying the decrease of 5HT1A receptors expression in the raphe nuclei of PS rats. © 2016 IBRO.


Tazzite A.,Genetics and Molecular Pathology Laboratory | Jouhadi H.,Ibn Rochd University Hospital | Nadifi S.,Genetics and Molecular Pathology Laboratory | Aretini P.,University of Pisa | And 4 more authors.
Gynecologic Oncology | Year: 2012

Objective: Breast cancer is the most common female cancer in Morocco. About 5 to 10% are due to hereditary predisposition and mutations in BRCA1 and BRCA2 genes are responsible for an important proportion of high-risk breast/ovarian cancer families. The relevance of BRCA1/2 mutations in the Moroccan population was not studied. The main objective of this study is to investigate the spectrum of BRCA1 and BRCA2 germline mutations in early onset and familial breast/ovarian cancer among Moroccan women. Methods: We screened the entire coding sequences and intron/exon boundaries of BRCA1 and BRCA2 genes in 40 patients by direct sequencing. Results: Nine pathogenic mutations were detected in ten unrelated families, five deleterious mutations in BRCA1 gene and four mutations in BRCA2 gene. Four novel mutations were found: one in BRCA1 (c.2805delA/2924delA) and three in BRCA2 (c.3381delT/3609delT; c.7110delA/7338delA and c.7235insG/7463insG). We also identified 51 distinct polymorphisms and unclassified variants (three described for the first time). Conclusions: Our data suggest that BRCA1 and BRCA2 mutations are responsible for a significant proportion of familial breast cancer in Moroccan patients. Therefore full BRCA1/2 screening should be offered to patients with a family history of breast/ovarian cancer. © 2012 Elsevier Inc. All rights reserved.


PubMed | Institute Pasteur, Hassan II University and Genetics and Molecular Pathology Laboratory
Type: Journal Article | Journal: European journal of medical genetics | Year: 2016

Deafness is one of the most common genetic diseases in humans and is subject to important genetic heterogeneity. The most common cause of non syndromic hearing loss (NSHL) is mutations in the GJB2 gene. This study aims to update and evaluate the spectrum of GJB2 allele variants in 152 Moroccan multiplex families with non syndromic hearing loss. Seven different mutations were detected: c.35delG, p.V37I, p.E47X, p.G200R, p.Del120E, p.R75Q, the last three mutations were described for the first time in Moroccan deaf patients, in addition to a novel nonsense mutation, the c.385G>T which is not referenced in any database. Sixty six families (43.42%) have mutations in the coding region of GJB2, while the homozygous c.35delG mutation still to date the most represented 51/152 (33.55%). The analysis of the geographical distribution of mutations located in GJB2 gene showed more allelic heterogeneity in the north and center compared to the south of Morocco. Our results showed that the GJB2 gene is a major contributor to non syndromic hearing loss in Morocco. Thus, this report of the GJB2 mutations spectrum all over Morocco has an important implication for establishing a suitable molecular diagnosis.


PubMed | Genetics and Molecular Pathology Laboratory, Ibn Rochd University Hospital and Institute Pasteur du Maroc
Type: | Journal: BMC cancer | Year: 2015

Identification of specific mutations in cancer patients may lead to the discovery of genes, which can affect susceptibility and/or prognosis. It has previously been reported that mutations in BRCA1 and BRCA2 genes are linked to breast cancer. Here, we evaluated the use of the High Resolution Melting (HRM) approach to screen for mutations in exon 11 of BRCA1 gene in Moroccan patients.HRM analysis was used to screen exon 11 from 71 breast cancer patients in order to detect different variants. Conventional Sanger sequencing was used to confirm the presence of possible mutations. Distribution of different SNPs was determined by SNaPshot analysis software.In order to assess the efficacy of the HRM approach to screen for mutations, especially in diagnosis, we first used two samples with previously known mutations, 2924delA and 3398delC. Indeed, these previously known sequence variants were detected by the HRM approach and yielded melting curves with atypical shape relative to wild-type control sequences. We then analyzed, 69 samples from breast cancer patients using the HRM method, and were able to detect two samples with atypical curves. Sequencing of the two samples, using the conventional Sanger approach, confirmed the presence of the same SNP (c.2612C>T) in both samples.Our results strongly suggest that the HRM approach represents a reliable and highly sensitive method for mutation scanning, especially in diagnosis.


Said N.,Laboratory of Pharmacology | Lakehayli S.,Laboratory of Pharmacology | El Khachibi M.,Genetics and Molecular Pathology Laboratory | El Ouahli M.,Sultan Moulay Slimane University | And 3 more authors.
Neuroscience | Year: 2015

Prenatal stress (PS) can induce several long-lasting behavioral and molecular abnormalities in rats. It can also be considered as a risk factor for many psychiatric diseases like schizophrenia, depression or PTSD and predispose to addiction. In this study, we investigated the effect of prenatal stress on the reinforcing properties of nicotine in the CPP paradigm. Then, we examined the mRNA expression of the D2 dopaminergic receptors using the quantitative real-time PCR technique in the nucleus accumbens (NAcc). We found that prenatally stressed rats exhibited a greater place preference for the nicotine-paired compartment than the control rats. Moreover, we observed an overexpression of the DRD2 gene in adult offspring stressed in utero and a downregulation in the PS NIC group (PS rats treated with nicotine) compared with their control counterparts (C NIC).These data suggest that maternal stress can permanently alter the offspring's addictive behavior and D2 receptors' expression. © 2015 IBRO.


Lakehayli S.,Laboratory of Pharmacology | Said N.,Laboratory of Pharmacology | Khachibi M.E.,Genetics and Molecular Pathology Laboratory | Ouahli M.E.,Sultan Moulay Slimane University | And 3 more authors.
Neuroscience Letters | Year: 2015

Early life stress during the gestational period alters specific neuronal circuits leading to behavioral alterations later in life. In the present study, we assessed the effects of prenatal stress and repeated benzodiazepine administration on dopamine receptor 2 expression in the nucleus accumbens of adult offspring.Our results show elevated Drd2 expression levels in the nucleus accumbens (NAcc) of prenatally stressed rats compared to control subjects, while repeated diazepam administration in adulthood down-regulated Drd2 expression and prevented the effect of prenatal stress. These observations suggest that prenatal stress may induce permanent alterations in the corticolimbic pathway implicated in drug-seeking behavior. © 2015 Elsevier Ireland Ltd.


PubMed | Genetics and Molecular Pathology Laboratory, Sultan Moulay Slimane University and Laboratory of Pharmacology
Type: | Journal: Neuroscience | Year: 2016

Early-life events have long-term effects on brain structures and cause behavioral alterations that persist into adulthood. The present experiments were designed to investigate the effects of prenatal stress on diazepam-induced withdrawal syndrome and serotonin-1A (5HT1A) receptor expression in the raphe nuclei of adult offspring. The results of the present study reveal that maternal exposure to chronic footshock stress increased the anxiety-like behavior in the prenatally stressed (PS) animals withdrawn from chronic diazepam (2.5mg/kg/day i.p for 1week). Moreover, prenatal stress induced a down-regulation of 5HT1A mRNA in the raphe nuclei of adult offspring. To our knowledge, this study is the first to demonstrate that maternal exposure to chronic footshock stress enhances diazepam withdrawal symptoms and alters 5HT1A receptor gene expression in the raphe nuclei of adult offspring. Thus, more studies are needed to clarify the mechanisms underlying the decrease of 5HT1A receptors expression in the raphe nuclei of PS rats.


PubMed | Genetics and Molecular Pathology Laboratory, Sultan Moulay Slimane University and Laboratory of Pharmacology
Type: | Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience | Year: 2015

Maternal distress has often been associated with cognitive deficiencies and drug abuse in rats. This study examined these behavioral effects in offspring of mothers stressed during gestation. To this end, pregnant dams were subjected to daily electric foot shocks during the last 10 days of pregnancy. We measured litter parameters and body weights of the descendants after weaning (21 days) and at adulthood (80 days). Afterwards, prenatally stressed and control rats performances in the novel object recognition test were compared in order to evaluate their memory while others underwent the Water consumption test to assess the nicotine withdrawal intensity after perinatal manipulations. Meanwhile, another set of rats were sacrificed and 5HT1A receptors mRNA expression was measured in the raphe nuclei by quantitative Real Time PCR. We noticed no significant influence of maternal stress on litter size and body weight right after weaning. However, control rats were heavier than the stressed rats in adulthood. The results also showed a significant decrease in the recognition score in rats stressed in utero compared to the controls. Moreover, a heightened anxiety symptom was observed in the prenatally stressed offspring following nicotine withdrawal. Additionally, the Real Time PCR method revealed that prenatal stress induced a significant decrease in 5HT1A receptors levels in the raphe nuclei. Nicotine had a similar effect on these receptors expression in both nicotine-treated control and prenatally stressed groups. Taken together, these findings suggest that the cognitive functions and drug dependence can be triggered by early adverse events in rats.


PubMed | Genetics and Molecular Pathology Laboratory, Sultan Moulay Slimane University and Laboratory of Pharmacology
Type: | Journal: Neuroscience letters | Year: 2015

Early life stress during the gestational period alters specific neuronal circuits leading to behavioral alterations later in life. In the present study, we assessed the effects of prenatal stress and repeated benzodiazepine administration on dopamine receptor 2 expression in the nucleus accumbens of adult offspring. Our results show elevated Drd2 expression levels in the nucleus accumbens (NAcc) of prenatally stressed rats compared to control subjects, while repeated diazepam administration in adulthood down-regulated Drd2 expression and prevented the effect of prenatal stress. These observations suggest that prenatal stress may induce permanent alterations in the corticolimbic pathway implicated in drug-seeking behavior.


Tazzite A.,Genetics and Molecular Pathology Laboratory
Ethiopian journal of health sciences | Year: 2013

Breast cancer is the most common cancer affecting women all over the world. In addition to hormonal and environmental causes, family history is emerging as an important risk factor in the etiology of this disease. The aim of the present study is thus to compare the clinico-pathological features of familial and sporadic breast cancer in Moroccan patients. A comparative retrospective cohort study was conducted on 570 women with familial and sporadic breast cancer who were diagnosed and treated in the Oncology Center of Ibn Rochd University Hospital in 2009. Data on breast cancer risk factors and clinico-pathological characteristics of the tumors were extracted from patients' medical records. Familial cases represented 18.4% of breast cancer patients. The age of onset appears to be earlier in familial breast cancers (P=0.0024). There were no significant differences between familial and sporadic groups according to histological type, tumor size and estrogen receptor status. However, Scarff-Bloom-Richardson grade III was found in 43.8% of familial cases vs 26.7% of sporadic cases (P=0.0127) and the lymph node involvement was observed in 72.4% of familial cases vs 58.9% in sporadic cases (P=0.0213). Moreover, familial breast cancer patients present especially progesterone receptor-negative tumors (P=0.0380). Our initial significant findings show that familial breast cancer seems to affect young women and tends to present high Scarff-Bloom-Richardson grade tumors with lymph node involvement and absence of progesterone receptors. These preliminary results may be useful as clinical marker to identify familial breast cancer allowing the development of careful follow-up for this patients subtype.

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