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Article ; Online: A Distinctive Pattern of Diversity for the

Mourali-Chebil, Soufia / Elkamel, Sarra / Boussetta, Sami / Pakstis, Andrew J / Kidd, Kenneth K / Benammar-Elgaaied, Amel / Cherni, Lotfi

Human biology

2023 Volume 93, Issue 3, Page(s) 163–177

Abstract: ... ...

Abstract	The
MeSH term(s)	Humans ; Africa, Northern ; Amino Acids ; Biological Assay ; Forensic Medicine ; Nucleotides
Chemical Substances	Amino Acids ; Nucleotides ; taste receptors, type 2
Language	English
Publishing date	2023-09-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1116-2
ISSN	1534-6617 ; 0018-7143
ISSN (online)	1534-6617
ISSN	0018-7143
DOI	10.1353/hub.2021.0009
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Article ; Online: New Insight into the human genetic diversity in North African populations by genotyping of SNPs in DRD3, CSMD1 and NRG1 genes.

Mestiri, Souhir / Boussetta, Sami / Pakstis, Andrew J / El Kamel, Sarra / Ben Ammar El Gaaied, Amel / Kidd, Kenneth K / Cherni, Lotfi

Molecular genetics & genomic medicine

2022 Volume 10, Issue 3, Page(s) e1871

Abstract: Background: The single nucleotide polymorphisms (SNPs) of the dopamine D3 receptor (DRD3), the CUB and sushi multiple domains 1 (CSMD1) and the neuregulin 1 (NRG1) genes were used to study the genetic diversity and affinity among North African ... ...

Abstract	Background: The single nucleotide polymorphisms (SNPs) of the dopamine D3 receptor (DRD3), the CUB and sushi multiple domains 1 (CSMD1) and the neuregulin 1 (NRG1) genes were used to study the genetic diversity and affinity among North African populations and to examine their genetic relationships in worldwide populations. Methods: The rs3773678, rs3732783 and rs6280 SNPs of the DRD3 gene located on chromosome 3, the rs10108270 SNP of the CSMD1 gene and the rs383632, rs385396 and rs1462906 SNPs of the NRG1 gene located on chromosome 8 were analysed in 366 individuals from seven North African populations (Libya, Kairouan, Mehdia, Sousse, Kesra, Smar and Kerkennah). Results: The low values of F Conclusions: The Kairouan population exhibited a relatively low rate of genetic variability. The North African population has undergone significant gene flow but also evolutionary forces that have made it genetically distinct from other populations.
MeSH term(s)	Blacks ; Genotype ; Haplotypes ; Humans ; Membrane Proteins/genetics ; Neuregulin-1/genetics ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D3/genetics ; Tumor Suppressor Proteins/genetics ; United States
Chemical Substances	CSMD1 protein, human ; DRD3 protein, human ; Membrane Proteins ; NRG1 protein, human ; Neuregulin-1 ; Receptors, Dopamine D3 ; Tumor Suppressor Proteins
Language	English
Publishing date	2022-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2734884-2
ISSN	2324-9269 ; 2324-9269
ISSN (online)	2324-9269
ISSN	2324-9269
DOI	10.1002/mgg3.1871
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Article: Genetic diversity of the North African population revealed by the typing of SNPs in the DRD2/ANKK1 genomic region

Mestiri, Souhir / Boussetta, Sami / Pakstis, Andrew J / Elkamel, Sarra / Elgaaied, Amel Ben Ammar / Kidd, Kenneth K / Cherni, Lotfi

Elsevier B.V. Gene. 2021 Apr. 20, v. 777

2021

Abstract: The dopamine – related genes, like dopamine D2 receptor (DRD2) gene and ankyrin repeat and kinase domain containing 1 (ANKK1) gene are implicated in neurological functions. Some polymorphisms of the DRD2/ANKK1 locus (TaqIA, TaqIB, TaqID) have been used ... ...

Abstract	The dopamine – related genes, like dopamine D2 receptor (DRD2) gene and ankyrin repeat and kinase domain containing 1 (ANKK1) gene are implicated in neurological functions. Some polymorphisms of the DRD2/ANKK1 locus (TaqIA, TaqIB, TaqID) have been used to study genetic diversity and the evolution of human populations. The present investigation aims to assess the genetic diversity in seven North African populations in order to explore their genetic structure and to compare them to others worldwide populations studied for the same locus.Nine single nucleotide polymorphisms (SNPs) from the DRD2/ANKK1 locus (rs1800497 TaqIA, rs2242592, rs1124492, rs6277, rs6275, rs1079727, rs2002453, rs2234690 and rs1079597 TaqIB) were typed in 366 individuals from seven North African populations: six from Tunisia (Sousse, Smar, Kesra, Kairouan, Mehdia and Kerkennah) and one from Libya.The allelic frequencies of rs2002453 and rs2234690 were higher in the Smar population than in the other North African populations. More, the Smar population showed the lowest average heterozygosity (0.313). The principal component analysis (PCA) showed that the Smar population was clearly separated from others. Furthermore, linkage disequilibrium analysis shown a high linkage disequilibrium in the North African population and essentially in Smar population. Comparison with other world populations has shown that the heterozygosity of North African population was very close to that of the African and European populations. The PCA and the haplotypic analysis suggested the presence of an important Eurasian genetic component for the North African population.These results suggested that the Smar population was isolated from the others North Africans ones by its peculiar genetic structure because of isolation, endogamy and genetic drift. On the other hand, the North African population is characterized by a multi ancestral gene pool from Eurasia and sub-Saharan Africa due to human migration since prehistoric times.
Keywords	dopamine ; dopamine receptors ; evolution ; gene pool ; genes ; genetic drift ; genetic variation ; genomics ; heterozygosity ; humans ; immigration ; linkage disequilibrium ; loci ; principal component analysis ; Eurasia ; Sub-Saharan Africa ; Tunisia
Language	English
Dates of publication	2021-0420
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145466
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Article ; Online: Association of a common genetic variant (insertion/deletion) in ACE gene with prostate cancer susceptibility in a Tunisian population.

Said, Rahma / Jenni, Rim / Boussetta, Sami / Ammous, Feryel / Zouari, Skander / Zaghbib, Selim / Chakroun, Marouene / Derouiche, Amine / Chebil, Mohamed / Ouerhani, Slah

Journal of clinical laboratory analysis

2021 Volume 36, Issue 1, Page(s) e24129

Abstract: Background: Angiotensin-converting enzyme (ACE) plays a pivotal role in several pathologies including cancers. The association of insertion/deletion (I/D) polymorphism of the ACE gene with prostate cancer (PC) risk remains controversial. We aimed to ... ...

Abstract	Background: Angiotensin-converting enzyme (ACE) plays a pivotal role in several pathologies including cancers. The association of insertion/deletion (I/D) polymorphism of the ACE gene with prostate cancer (PC) risk remains controversial. We aimed to investigate for the first time, to our Knowledge, in North Africa the potential relationship between ACE I/D polymorphism with PC susceptibility and clinical outcomes of PC patients. Methods: This case-control study included 143 healthy individuals and 124 patients diagnosed with PC. Using genomic DNA, the samples were genotyped for ACE I/D polymorphism by polymerase chain reaction (PCR). Results: We found that The D allele is significantly associated with an increased risk of PC and D/D + D/I genotypes were at 3 times increased risk of PC ([p = 0.005], OR = 2.95, IC 95% = 1.26-7.09) compared with I/I genotype (p = 0.003, OR = 0.3, IC 95% = 0.12-0.74). We observed an association between D/D and D/I genotypes with advanced age (≥70 years) (p = 0.014; r Conclusion: The ACE I/D polymorphism is likely to predispose to PC and could play a role in PC progression and aggressiveness.
MeSH term(s)	Aged ; Aged, 80 and over ; Alu Elements/genetics ; Case-Control Studies ; Genetic Predisposition to Disease/epidemiology ; Genetic Predisposition to Disease/genetics ; Humans ; INDEL Mutation/genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/genetics ; Polymorphism, Genetic/genetics ; Prostatic Neoplasms/epidemiology ; Prostatic Neoplasms/genetics ; Tunisia
Chemical Substances	ACE protein, human (EC 3.4.15.1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2021-11-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	645095-7
ISSN	1098-2825 ; 0887-8013
ISSN (online)	1098-2825
ISSN	0887-8013
DOI	10.1002/jcla.24129
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Article ; Online: Genetic diversity of the North African population revealed by the typing of SNPs in the DRD2/ANKK1 genomic region.

Mestiri, Souhir / Boussetta, Sami / Pakstis, Andrew J / Elkamel, Sarra / Elgaaied, Amel Ben Ammar / Kidd, Kenneth K / Cherni, Lotfi

Gene

2021 Volume 777, Page(s) 145466

Abstract: The dopamine - related genes, like dopamine D2 receptor (DRD2) gene and ankyrin repeat and kinase domain containing 1 (ANKK1) gene are implicated in neurological functions. Some polymorphisms of the DRD2/ANKK1 locus (TaqIA, TaqIB, TaqID) have been used ... ...

Abstract	The dopamine - related genes, like dopamine D2 receptor (DRD2) gene and ankyrin repeat and kinase domain containing 1 (ANKK1) gene are implicated in neurological functions. Some polymorphisms of the DRD2/ANKK1 locus (TaqIA, TaqIB, TaqID) have been used to study genetic diversity and the evolution of human populations. The present investigation aims to assess the genetic diversity in seven North African populations in order to explore their genetic structure and to compare them to others worldwide populations studied for the same locus. Nine single nucleotide polymorphisms (SNPs) from the DRD2/ANKK1 locus (rs1800497 TaqIA, rs2242592, rs1124492, rs6277, rs6275, rs1079727, rs2002453, rs2234690 and rs1079597 TaqIB) were typed in 366 individuals from seven North African populations: six from Tunisia (Sousse, Smar, Kesra, Kairouan, Mehdia and Kerkennah) and one from Libya. The allelic frequencies of rs2002453 and rs2234690 were higher in the Smar population than in the other North African populations. More, the Smar population showed the lowest average heterozygosity (0.313). The principal component analysis (PCA) showed that the Smar population was clearly separated from others. Furthermore, linkage disequilibrium analysis shown a high linkage disequilibrium in the North African population and essentially in Smar population. Comparison with other world populations has shown that the heterozygosity of North African population was very close to that of the African and European populations. The PCA and the haplotypic analysis suggested the presence of an important Eurasian genetic component for the North African population. These results suggested that the Smar population was isolated from the others North Africans ones by its peculiar genetic structure because of isolation, endogamy and genetic drift. On the other hand, the North African population is characterized by a multi ancestral gene pool from Eurasia and sub-Saharan Africa due to human migration since prehistoric times.
MeSH term(s)	Adult ; Africa, Northern/ethnology ; African Continental Ancestry Group ; Alleles ; Ethnic Groups/genetics ; Female ; Gene Frequency/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Genomics ; Genotype ; Genotyping Techniques ; Haplotypes/genetics ; Heterozygote ; Human Migration ; Humans ; Linkage Disequilibrium/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Protein-Serine-Threonine Kinases/genetics ; Receptors, Dopamine D2/genetics
Chemical Substances	DRD2 protein, human ; Receptors, Dopamine D2 ; ANKK1 protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-01-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145466
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Article ; Online: STAT3 polymorphisms in North Africa and its implication in breast cancer.

Ziadi, Wafa / Boussetta, Sami / Elkamel, Sarra / Pakstis, Andrew J / Kidd, Kenneth K / Medimegh, Imen / Ben Ammar Elgaaied, Amel / Cherni, Lotfi

Molecular genetics & genomic medicine

2021 Volume 9, Issue 8, Page(s) e1744

Abstract: Background: Only a few studies have investigated the association of single nucleotide polymorphisms in STAT3 gene with the susceptibility to cancer and response to chemotherapy. Our aim was to determine the allele frequencies of rs3869550, rs957971, and ...

Abstract	Background: Only a few studies have investigated the association of single nucleotide polymorphisms in STAT3 gene with the susceptibility to cancer and response to chemotherapy. Our aim was to determine the allele frequencies of rs3869550, rs957971, and rs7211777 at the STAT3 gene in North African populations and compare them to 1000 genomes populations, and to investigate their relation with cancer. Methods: The targeted SNPs have been analyzed in six Tunisian populations and a sample of Libyans using TaqMan® Assay. The results were compared to 1000 Genomes Project population samples. Targeting of the regions encompassing the three SNPs by micro-ARN was assessed using miR databases. Results: The analysis of the 3 SNPs showed that North African populations were close to South Asians. As expected, African populations presented a significant frequency of the ancestral CCG haplotype in contrast to other populations where the fully derived TGA haplotype was more frequent. The presence and diversity of rare haplotypes at STAT3 in North African populations could have been generated by recombination between the two major haplotypes. A screening of the micro-RNA databases showed that the STAT3 region with the mutated allele of rs7211777 (G>A) could be targeted by miR hsa-miR-3606-5p, which also targets genes involved in breast cancer.
MeSH term(s)	Breast Neoplasms/genetics ; Female ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; STAT3 Transcription Factor/genetics ; Tunisia
Chemical Substances	STAT3 Transcription Factor ; STAT3 protein, human
Language	English
Publishing date	2021-07-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2734884-2
ISSN	2324-9269 ; 2324-9269
ISSN (online)	2324-9269
ISSN	2324-9269
DOI	10.1002/mgg3.1744
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Article ; Online: Investigation of the genetic structure of Kabyle and Chaouia Algerian populations through the polymorphism of Alu insertion markers.

Badache, Hocine / Boussetta, Sami / Elgaaeid, Amel Benammar / Cherni, Lotfi / El-Khil, Houssein Khodjet

Annals of human biology

2019 Volume 46, Issue 2, Page(s) 150–159

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Algeria ; Alleles ; Alu Elements ; Gene Frequency ; Genetic Variation ; Humans ; Polymorphism, Genetic
Language	English
Publishing date	2019-04-09
Publishing country	England
Document type	Journal Article
ZDB-ID	186656-4
ISSN	1464-5033 ; 0301-4460
ISSN (online)	1464-5033
ISSN	0301-4460
DOI	10.1080/03014460.2019.1588994
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Article: Mitochondrial DNA and Alzheimer’s disease: a first case–control study of the Tunisian population

Ben Salem, Nesrine / Boussetta, Sami / de Rojas, Itziar / Moreno-Grau, Sonia / Montrreal, Laura / Mokni, Narjes / Mahmoud, Imene / Younes, Samia / Daouassi, Nizar / Frih-Ayed, Mahbouba / Hammami, Afef / Ben Ammar Elgaaied, Amel / Ruiz, Agustín / Cherni, Lotfi

Molecular biology reports. 2022 Mar., v. 49, no. 3

2022

Abstract: BACKGROUND: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial ... ...

Abstract	BACKGROUND: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial alteration has been proposed as a possible cause of AD. Therefore, several studies have focused on finding an association between inherited mitochondrial DNA variants and AD onset. METHODS: In this study, we looked, for the first time, for a potential association between mitochondrial haplogroups or polymorphisms and AD in the Tunisian population. We also evaluated the distribution of the major genetic risk factor for AD, the apolipoprotein E epsilon 4 (APOE ε4), in this population. In total, 159 single-nucleotide polymorphisms (SNPs) of mitochondrial DNA haplogroups were genotyped in 254 individuals (58 patients and 196 controls). An additional genotyping of APOE ε4 was performed. RESULTS: No significant association between mitochondrial haplogroups and AD was found. However, two individual SNPs, A5656G (p = 0.03821, OR = 10.46) and A13759G (p = 0.03719, OR = 10.78), showed a significant association with AD. APOE 4 was confirmed as a risk factor for AD (p = 0.000014). CONCLUSION: Our findings may confirm the absence of a relation between mitochondrial haplogroups and AD and support the possible involvement of some inherited variants in the pathogenicity of AD.
Keywords	apolipoprotein E ; case-control studies ; etiology ; genotyping ; mitochondria ; mitochondrial DNA ; molecular biology ; neurodegenerative diseases ; pathogenicity ; risk factors
Language	English
Dates of publication	2022-03
Size	p. 1687-1700.
Publishing place	Springer Netherlands
Document type	Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-06978-7
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Article: Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort [Erratum: February 2022, v.49(2); p.1259]

Hemissi, Imen / Boussetta, Sami / Dallali, Hamza / Hellal, Faycel / Durand, Geoffroy / Voegele, Catherine / Ayed, Haroun / Zaghbib, Selim / Naimi, Zeineb / Ayadi, Mouna / Chebil, Mohamed / Mckay, James / Le Calvez-Kelm, Florence / Ouerhani, Slah

Molecular biology reports. 2022 Feb., v. 49, no. 2

2022

Abstract: BACKGOUND: Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case–control study was to evaluate the implication of a selected SNP panel in the risk of BCa ... ...

Abstract	BACKGOUND: Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case–control study was to evaluate the implication of a selected SNP panel in the risk of BCa development in a Tunisian cohort. We were also interested in studying the interaction between this predictive panel and environmental risk factors. METHODS: The case/control cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) was composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology). RESULTS: We have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR 2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non–smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A > G), ARNT/ rs1889740 (C > T) or GSTA4/rs17614751 (G–A) were respectively at 2.775, 3.069 and 6.608-fold increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa classes. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype. CONCLUSIONS: The determined association between environmental factors, genetic variations and the risk of Bca development may provide additional information to urologists that may help them for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies.
Keywords	carcinogenesis ; case-control studies ; decision support systems ; genes ; genotyping ; heterozygosity ; homozygosity ; molecular biology ; risk reduction ; tobacco use ; urinary bladder neoplasms
Language	English
Dates of publication	2022-02
Size	p. 1233-1258.
Publishing place	Springer Netherlands
Document type	Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-06951-4
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Article ; Online: Ancient and recent Middle Eastern maternal genetic contribution to North Africa as viewed by mtDNA diversity in Tunisian Arab populations.

Elkamel, Sarra / Boussetta, Sami / Khodjet-El-Khil, Houssein / Benammar Elgaaied, Amel / Cherni, Lotfi

American journal of human biology : the official journal of the Human Biology Council

2018 Volume 30, Issue 3, Page(s) e23100

Abstract: Objectives: Through previous mitochondrial DNA studies, the Middle Eastern maternal genetic contribution to Tunisian populations appears limited. In fact, most of the studied communities were cosmopolitan, or of Berber or Andalusian origin. To provide ... ...

Abstract	Objectives: Through previous mitochondrial DNA studies, the Middle Eastern maternal genetic contribution to Tunisian populations appears limited. In fact, most of the studied communities were cosmopolitan, or of Berber or Andalusian origin. To provide genetic evidence for the actual contribution of Middle Eastern mtDNA lineages to Tunisia, we focused on two Arab speaking populations from Kairouan and Wesletia known to belong to an Arab genealogical lineage. Materials and methods: A total of 114 samples were sequenced for the mtDNA HVS-I and HVS-II regions. Using these data, we evaluated the distribution of Middle Eastern haplogroups in the study populations, constructed interpolation maps, and established phylogenetic networks allowing estimation of the coalescence time for three specific Middle Eastern subclades (R0a, J1b, and T1). Results: Both studied populations displayed North African genetic structure and Middle Eastern lineages with a frequency of 12% and 28.12% in Kairouan and Wesletia, respectively. TMRCA estimates for haplogroups T1a, R0a, and J1b in Tunisian Arabian samples were around 15 000 YBP, 9000 to 5000 YBP, and 960 to 600 YBP, respectively. Conclusions: The Middle Eastern maternal genetic contribution to Tunisian populations, as to other North African populations, occurred mostly in deep prehistory. They were brought in different migration waves during the Upper Paleolithic, probably with the expansion of Iberomaurusian culture, and during Epipaleolithic and Early Neolithic periods, which are concomitant with the Capsian civilization. Middle Eastern lineages also came to Tunisia during the recent Islamic expansion of the 7th CE and the subsequent massive Bedouin migration during the 11th CE.
MeSH term(s)	Arabs/genetics ; DNA, Mitochondrial/analysis ; Genetic Variation ; Haplotypes/genetics ; Phylogeny ; Sequence Analysis, DNA ; Tunisia
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2018-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1025339-7
ISSN	1520-6300 ; 1042-0533
ISSN (online)	1520-6300
ISSN	1042-0533
DOI	10.1002/ajhb.23100
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