RESUMEN
A total of 149 unrelated and healthy individuals comprising: Tunisian Berbers, Tunisians with Andalusian origin and Libyans were typed with the SNPforID 34-plex ancestry informative marker (AIM) SNP panel. Results of 31 of the 34 SNPs are presented and no deviations from Hardy-Weinberg equilibrium were observed after Bonferroni correction (p=0.00161) except rs722098 (p=0.0000). Comparisons of allele frequencies showed high divergence values between North Africans and Europeans (δ>30%) in markers: rs4540055 (allele A) and rs16891982. Our study adds data that can be used as training set genotypes for future ancestry investigations in forensic cases and suggests these AIM-SNPs can successfully differentiate North Africans and Mediterranean Europeans.
Asunto(s)
Genética de Población , Polimorfismo de Nucleótido Simple , Frecuencia de los Genes , Humanos , Libia , TúnezRESUMEN
BACKGROUND: The most recent Alu insertions reveal different series of characteristics such as stability that make them particularly suitable genetic markers for human biological studies. AIM: Six human-specific Alu insertion polymorphisms were typed in two Tunisian Berber populations with the aim of analysing the genetic diversity of these two communities and the genetic relationships between this region of North Africa and other populations. SUBJECTS AND METHODS: Forty-seven Berbers from Sejnane and 33 from Takrouna were sampled. Alu insertion polymorphism was analysed using PCR with loci specific primers. RESULTS: A similar level of gene diversity was detected in Sejnane and Takrouna populations. PC results revealed genetic affinities between these two populations and some Eurasian populations (Germany, Genova and Syria). In contrast, there is a differentiation between these two Berber communities and North African and Iberian populations. CONCLUSION: The results of this study confirm the heterogeneity of Berbers in North Africa, which suggests their diverse origins. In the case of Sejnane and Takrouna populations, these results are in line with an ancient Euro Mediterranean background that has already been studied by archaeologists, particularly for the population of Sejnane.
Asunto(s)
Elementos Alu , Etnicidad/genética , Variación Genética , Marcadores Genéticos , Geografía , Humanos , Mutagénesis Insercional , Filogenia , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , TúnezRESUMEN
OBJECTIVES: Sporadic colorectal cancer is influenced by numerous single nucleotide polymorphisms (SNPs), each with minor effects on the cancer risk. This study seeks to determine whether there is any association of the I1307K, E1317Q and D1822V variants within the Adenomatous polyposis coli gene (APC) and risk to develop colorectal cancer in Tunisian population. METHODS: Direct sequencing was used to investigate three SNPs in the APC in 48 Tunisian sporadic colorectal cancer cases and 63 controls. RESULTS: There was no statistically significant association between the I1307K, E1317Q and D1822V variants investigated and colorectal cancer risk. CONCLUSION: The lack of association may show that these variants selected for this study are not involved in the colorectal carcinogenic process. Otherwise, the eventual biological effect is so little to go undetected, unless increasing the sample size.
Asunto(s)
Proteína de la Poliposis Adenomatosa del Colon/genética , Neoplasias Colorrectales/genética , Genes APC , Variación Genética , Mutación Missense , Polimorfismo de Nucleótido Simple , Sustitución de Aminoácidos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , ADN/sangre , ADN/genética , ADN/aislamiento & purificación , Cartilla de ADN , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Etnicidad/genética , Homocigoto , Humanos , Estadificación de Neoplasias , Grupos Raciales/genética , Factores de Riesgo , TúnezRESUMEN
Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells. It is highly expressed by all epithelial cells and represents a useful indicator of epithelial differentiation. The soluble fragment of CK19 (CYFRA 21-1) can be a useful circulating tumor marker and can be detected in the serum of cancer patients. The development of metastasis in patients with cancer of epithelial origin is due to the migration of tumor cells from the original tumor to distant organs. In order to detect micrometastasis in patients with breast cancer, we evaluated and compared CK19 gene expression using RT-PCR in blood samples collected from 80 healthy women and 80 patients with localized or metastatic breast cancer. The concentration of the soluble CK19 fragment CYFRA 21-1 was measured in serum of all study subjects by radioimmunoassay employing specific monoclonal antibodies. The relationship between the expression of this molecular marker and clinical stage, tumor differentiation and CK19 mRNA transcripts was investigated. We found that CK19 mRNA expression in blood (as a direct index of the presence of circulating tumor cells) was not correlated with CYFRA 21-1.
Asunto(s)
Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Queratina-19/sangre , Queratinas/sangre , ARN Mensajero/sangre , Adulto , Antígenos de Neoplasias/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/secundario , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Queratina-19/genética , Queratinas/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Sensibilidad y Especificidad , TúnezRESUMEN
Hereditary breast cancer accounts for 3-8% of all breast cancers, with mutations in the BRCA1 and BRCA2 genes responsible for up to 30% of these. To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, we studied 36 patients who had at least one first degree relative with breast and/or ovarian cancer Thirty-four 34 patients were suggestive of the BRCA1 mutation and two were suggestive of the BRCA2 mutation, based on the presence of male breast cancer detected in their corresponding pedigrees. Four mutations in BRCA1 were detected, including a novel frame-shift mutation (c.211dupA) in two unrelated patients and three other frameshift mutations--c.4041delAG, c.2551delG and c.5266dupC. Our study is the first to describe the c.5266dupC mutation in a non-Jewish Ashkenazi population. Two frameshift mutations (c.1309del4 and c.5682insA) were observed in BRCA2. Nineteen percent (7/36) of the familial cases had deleterious mutations of the BRCA1 or BRCA2 genes. Almost all patients with deleterious mutations of BRCA1 reported a family history of breast and/or ovarian cancer in the index case or in their relatives. Our data are the first to contribute to information on the mutation spectrum of BRCA genes in Tunisia, and we give a recommendation for improving clinical genetic testing policy.
Asunto(s)
Neoplasias de la Mama/genética , Genes BRCA1 , Genes BRCA2 , Mutación , Femenino , Humanos , TúnezRESUMEN
BRCA1 is a tumor suppressor gene which is inactivated by mutation in familial breast and ovarian cancers. Over 300 different disease causing germ-line mutations have been described; 60% are unique to an individual family. This diversity and the large size of the gene lead us to search for a prescreening method for BRCA1 mutations. Since BRCA1 is a nuclear protein in normal cells, but reported by some authors to be cytoplasmic in breast tumor cells of patients with BRCA1 mutation, we evaluated immunohistochemistry as a prescreening technique to identify BRCA1 mutations in patients with familial presentation of breast cancer. Using a monoclonal antibody against the carboxy-terminal region of BRCA1, we performed immunohistochemistry on 18 tumor samples from patients with hereditary breast cancer. Cytoplasmic staining of BRCA1 was observed in 10 cases. Of the 18 tumors, 12 (66%) showed either BRCA mutation or BRCA1 accumulation or both, indicating that BRCA1 function might be lost in breast tumor cells not only through mutation, but also via abnormal cytoplasmic location. The immunohistochemical test used in this study would not be efficient as a pre-screening method of deleterious mutations, but it appeared useful to investigate tumor physiology.
Asunto(s)
Proteína BRCA1/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Proteína BRCA1/biosíntesis , Proteína BRCA1/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama Masculina/genética , Neoplasias de la Mama Masculina/metabolismo , Carcinoma Ductal de Mama/epidemiología , Carcinoma Ductal de Mama/genética , Citoplasma/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Linaje , Receptores de Estrógenos/biosíntesis , Receptores de Progesterona/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Túnez/epidemiologíaRESUMEN
North Africa is populated by many Arab- and Berber-speaking populations whose genetic history is still poorly understood. In this study, we analyse the HLA-DRB1 and DQB1 molecular diversity in three populations from the south of Tunisia--Berbers from Jerba, Berbers from Matmata and Arabs from Gabes--and we compare them to a large set of populations from the whole Mediterranean region. Among the three populations studied, the Berbers from Jerba are the most peculiar, as they diverge significantly from other North Africans while being genetically highly diversified and close to populations from the Near East. Thus, Jerba may have been a crossing point, in historical times, where colonization from the eastern Mediterranean area left significant genetic traces. By contrast, the populations from Matmata and Gabes are genetically similar to other Arab and Berber-speaking populations from different areas of the Maghrib, despite some peculiar allele and haplotype frequencies. At a larger scale, northwest Africa and southwest Europe are closely related according to these polymorphisms, while the populations from the eastern Mediterranean area are much more differentiated. The close genetic relatedness found for HLA among populations of the western Mediterranean region challenges previous results based on Y chromosome analyses, where the Gibraltar Strait appeared to constitute a main genetic barrier.
Asunto(s)
Variación Genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Alelos , Frecuencia de los Genes , Genética de Población , Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Haplotipos , Humanos , Región Mediterránea , TúnezRESUMEN
Jerba is an island situated in the South-East of Tunisia were some ethnic groups (Arabs, Berbers, Blacks, Jewishs and others) cohabit for centuries. The religion and cultural differences have represented an obstacle to a mixture between these groups. In order to evaluate the genetic differentiation between the muslim groups (Arabs, Berbers and Blacks), we have analysed the polymorphism of a mitochondrial DNA coding region. The cytochrome oxydase coding region (COII) was amplified by PCR in 57 Arabs, 42 Berbers and 16 Blacks. The amplified products were analysed by Restriction Fragment Length Polymorphism (RFLP). Genetic distances were calculated by using the AMOVA program. The values of these distances were significantly different between Arabs and Blacks, and between Berbers and Blacks but not between Arabs and Berbers. So That, to refine the evaluation of genetic diversity between Arabs and Berbers, we have analysed the polymorphism of a second mitochondrial coding region which encodes for the fifth unit of NADH deshydrogenase (ND5). Eleven haplotypes were defined from the resulting data of mitochondrial COII and ND5 polymorphism and a significant genetic distance between Arabs and Berbers was computed.