North African Populations Research Articles

Identification of novel mutations by targeted NGS in Moroccan families clinically diagnosed with a neuromuscular disorder

Background and aimsThe identification of underlying genes of genetic conditions has expanded greatly in the past decades, which has broadened the field of genes responsible for inherited neuromuscular diseases. We aimed to investigate mutations associated with neuromuscular disorders phenotypes in 2 Moroccan families. Material and methodsNext-generation sequencing combined with Sanger sequencing could assist with understanding the hereditary variety and underlying disease mechanisms in these disorders. ResultsTwo novel homozygous mutations were described in this study. The SIL1 mutation is the first identified in the Moroccan population, the mutation was identified as the main cause of Marinesco-Sjogren syndrome in one patient. While the second mutation identified in the fatty acid 2-hydroxylase gene (FA2H) was associated with the Spastic paraplegia 35 in another patient, both transmitted in an autosomal recessive pattern. Discussion and conclusionsThese conditions are extremely rare in the North African population and may be underdiagnosed due to overlapping clinical characteristics and heterogeneity of these diseases. We have reported in this study mutations associated with the diseases found in the patients. In addition, we have narrowed the phenotypic spectrum, as well as the diagnostic orientation of patients with neuromuscular disorders, who might have very similar symptoms to other disease groups.

Genetic analysis of sixteen autosomal STR loci in three Tunisian populations from Makthar, Nabeul and Sousse

Background Due to its strategic location, Tunisia witnessed the succession and influence of many civilisations throughout history. However, the majority of studies carried out on Tunisia are focussed on Barbarian ethnicity. Aim To estimate genetic diversity and genetic structure of three Tunisian populations using autosomal STRs. Subjects and methods 278 individuals were analysed for sixteen STRs. Allele frequencies and statistical parameters were determined. Results The studied populations showed genetic affinity with geographically close populations. AMOVA showed no genetic difference between the Tunisian populations. Nevertheless, the variance between the populations of the same group was significant, reflecting their heterogeneity even though they came from the same geographical area, and had the same ethnicity and complex demographic history. Conclusion Our results strongly supported the application of autosomal genetic markers in anthropological and forensic studies. The analyses conducted at the 15-loci level provide the resolution to assess the phylogenetic relationships among the populations examined and other geographically targeted worldwide populations, while the results resulting from the 10-loci studies provide an understanding of the relationships and origins of the North African populations. Furthermore, the current report demonstrates that the battery of autosomal STRs reported are useful, providing the power of discrimination for forensic and paternity analyses.

Genomewide association analysis of warfarin dose requirements in Middle Eastern and North African populations.

To date, there has been no genomewide association study (GWAS) from the Middle East and North African (MENA) region to identify genetic variants associated with warfarin dose variability using this approach. In this study, we aimed to conduct the first GWAS of warfarin dose requirements in patients from the MENA region. A total of 132 Qatari (discovery) and 50 Egyptians (replication) were genotyped using Illumina Multi‐Ethnic Global BeadChip Array. A GWAS was performed on log‐transformed weekly warfarin dose in the studied population, adjusting for clinical characteristics and ancestry. The genomewide signals from the discovery cohort were tested in the Egyptian cohort. A GWAS meta‐analysis, including the Qatari and Egyptian cohorts, was also performed and the output from this analysis was used in a gene‐based analysis. The discovery analysis in Qatari identified five genomewide single‐nucleotide polymorphisms (SNPs) in chromosome 16. These signals were replicated in the Egyptian cohort. Combining the two data through a GWAS meta‐analysis strengthened the association in chromosome 16 with VKORC1 rs9934438 being the lead genomewide signal (β = −0.17, 6 × 10−15). Other SNPs were identified in chromosome 10 at a p value less than 1 × 10−5. The genetic variants within VKORC1 rs9934438 and CYP2C9 rs4086116 explained 39% and 27% of the variability in the weekly warfarin dose requirement in the Qatari and Egyptians, respectively. This is the first GWAS of warfarin dose variability in the MENA region. It confirms the importance of VKORC1 and CYP2C9 variants in warfarin dose variability among patients from the MENA region.

Clinical predictors of response to clozapine in Tunisian patients with treatment resistant schizophrenia

IntroductionTreatment resistant schizophrenia (TRS), affecting approximately one-third of patients with schizophrenia, is associated with a serious impairment in global psychosocial functioning. Clozapine is the only licensed drug for TRS. However its prescription remains limited by its side effects requiring mandatory monitoring. The need to identify clinical factors associated with good response to clozapine in TRS has been established. The presence of ethnic differences in these factors and the scarcity of data on the Tunisian or more generally the North-African population warrants the conduct of a clinical study on the subject. The aim of this study was to investigate demographic, clinical, and biochemical patient characteristics as potential predictors of response to clozapine. MethodsThis is a cross-sectional and retrospective study, at the “F and A psychiatry departments” of Razi Hospital in Manouba, Tunisia. All patients, with DSM 5 diagnosis of schizophrenia in its resistant form, on clozapine for at least 12 months and who consulted from June 1, 2018 to November 30, 2018 were included. We investigated premorbid functioning by the premorbid adjusment scale, demographic and clinical characteristics, and clozapine plasma level as potential clozapine response predictors. The response to clozapine was defined by a total BPRS score of 35 or less. ResultsSixty-three patients were included in the study. The mean age at clozapine introduction was 30,84 ±9,25 years. The mean duration of clozapine treatment was 7,22 ± 4,02 years.There were 16 clozapine responders (25%) who had BPRS total scores below or equal to 35 and 47 non-responders (75%).A higher premorbid social functioning in childhood (p = 0,018) and early adolescence (p = 0,024) was associated with better response to clozapine. A delay clozapine initiation shorter than 7 years(p = 0,036), one atypical antipsychotic trial (p = 0,029) and schizophrenia paranoid subtype (p< 0.01) were found to be significantly predictive of good clozapine response. None of the demographic factors or biochemical characteristics were associated with clozapine response. ConclusionsOur work is consistent with previous studies suggesting the need for clinicians to be aware of the clinical predictors of a good response to clozapine to overcome their reluctance to prescribe it. It also highlighted the major prognostic role of premorbid adjustment in the clinical response to treatment. However, prospective studies including therapeutic drug monitoring would be very useful to better delineate the sub-group of patients to whom clozapine would benefit the most and to improve prescription modalities.

Indocyanine Green Fluorescence-Guided Sentinel Node Biopsy in Breast Cancer Within a North African Population: A Retrospective Study.

Radio isotopes and blue dyes alone or in combination are the most commonly used tracer agents in sentinel node (SN) biopsy for early breast cancer. Recent studies have found fluorescence method using indocyanine green (ICG) as a promising technology with fewer disadvantages. Retrospective analysis of our database that included patients with clinically node-negative breast cancer scheduled for breast surgery and SN biopsy between 2016 and January 2021. Patients who underwent detection using fluorescence-ICG were included in this study. A total of 47 patients were included. Median age was 50 (range: 24-78) years. Mean tumor size was 3.4 ± 1.5 cm. All patients received ICG injection and 11 received a combination of ICG and blue dye. Forty-five successful SN identifications with ICG were performed and 99 nodes retrieved. Eleven procedures were undertaken after initial systemic therapy. Twenty-four patients had at least one positive SN for malignancy. Mean follow up was 29.2 months and no axillary recurrence was noted during the study period. ICG appears to be a feasible and accurate method for SN biopsy with high identification rate. This is the first study of ICG in sentinel node biopsy in a North African population.

First characterization of congenital myasthenic syndrome type 5 in North Africa.

Congenital myasthenic syndromes (CMS) are associated with defects in the structure and the function of neuromuscular junctions. These rare disorders can result from mutations in the collagenic tail of endplate acetylcholinesterase (COLQ) essentially associated with autosomal recessive inheritance. With the lowered cost of genetic testing and increased access to next-generation sequencing, many mutations have been reported to date. In this study we identified the first COLQ homozygous mutation c.1193T>A in the North African population. This study outlines the genetic and phenotypic features of a CMS patient in a Moroccan family. It also describes a novel COLQ missense mutation associated with CMS-5. COLQ mutations are probably underdiagnosed in these North African populations, this is an issue as CMS-5 may be treated with ephedrine, and albuterol. Indeed, patients can seriously benefit and even recover after the treatment that should be planned according to genetic tests and clinical findings.

Deep analysis of the LRTOMTc.242G>A variant in non-syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies.

Autosomal recessive non‐syndromic hearing loss (ARNSHL) is the most common inherited sensory impairment. It is particularly frequent in North African populations who have a high rate of consanguineous marriage. The c.242G>A homozygous variant in LRTOMT gene was previously established as pathogenic and is associated with NSHL in both humans and mice. The aim of this study is to determine the carrier frequency for the LRTOMT c.242G>A variant and also to estimate its age in addition to evaluating its diagnostic potential as a deafness biomarker among various populations and ethnicities in Northern African countries. A total of 179 Tunisian and 34 Libyan unrelated deafness patients were screened for this variant. The homozygous c.242G>A variant was found in 5.02% and 2.94% in Tunisian and Libyan families, respectively. Subsequent screening for this variant in 263 healthy controls of various ethnicities (136 Tunisian Berbers, 32 Andalusian and 95 Tunisian from undefined ethnic origin) revealed higher frequency for the heterozygous state among Tunisians of Berber origin only (19.11%). Genotyping 7 microsatellite markers nearby the variant location in ARNSHL patients who had the homozygous variant revealed the same haplotype suggesting a common founder origin for this variant. The age of this variant was estimated to be between 2025 and 3425 years (this corresponds to 3400 years when the variant rate was set at 10−3 or 2600 years when the variant rate is set at 10−2), spreading along with the Berber population who migrated to North Africa. In conclusion, the LRTOMT c.242G>A homozygous variant could be used as a useful deafness biomarker for North African ARNSHL patients meanwhile the heterozygous variant could be utilized in genealogical studies for tracing those of the Berber ethnic group.

Anthropometric measurements of non-arthritic knees in an Egyptian population: an MRI-based study

BackgroundKnee anthropometric characteristics were evaluated for different ethnicities; however, data from North African populations are deficient. The primary aim was to investigate the Egyptian knees’ anthropometric characteristics as a representative of North African populations. Secondary aims are as follows: (1) to study the anthropometric gender difference, (2) to compare results with other ethnic groups, and (3) to study the mismatch in comparison to geometric characteristics of modern TKA implant designs.MethodsTwo hundred normal knee MRI scans (100 females and 100 males, aging from 18 to 60) were obtained for analysis. Linear measurements (anteroposterior (AP), mediolateral (ML), and aspect ratio (AR)) of the planned cut surface of the distal femur (f) and the proximal tibia (t) were evaluated.ResultsA significant difference between both sexes was found, males had larger measurements in anteroposterior [fAP: 60.97 ± 3.1 vs 54.78 ± 3.3 (P < 0.001), tAP: 46.89 ± 3.0 vs 41.35 ± 2.9 (P < 0.001)] and mediolateral [fML: 74.89 ± 3.2 vs 67.29 ± 3.7 (P < 0.001), tML: 76.01 ± 3.0 vs 67.26 ± 3.2 (P < 0.001)], the mean femoral and tibial AP and ML measurements were different from other ethnic groups. None of the seven studied TKA systems matched the largest ML or the smallest AP dimensions of the distal femur in the current study population.ConclusionA significant difference was found between males’ and females’ knee anthropometric characteristics. Some of the commonly used TKA implants in our area could not provide a perfect fit and coverage.Trial registrationClinicalTrials.gov identifier: NCT03622034, registered on July 28, 2018.

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers

BackgroundBreast cancer is the world’s most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations.MethodsA total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated.ResultsIn the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations.ConclusionOur study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.

Urban and industrial landscapes interact with microhabitat to predict occurrence of European Turtle Dove (Streptopelia turtur) in Mediterranean oases: Implications for conservation

The assessment of the impact of urban and industrial landscapes on the occurrence of vulnerable species is one key step in the view to maintaining them in environments that are becoming urbanised. In the present study, we aimed to investigate this issue with regards to the vulnerable European Turtle Dove (TD) (Streptopelia turtur) in the coastal Mediterranean oases. Here, we used data on a series of variables, including microhabitat and urban-industrial landscapes, to identify the best predictors that cause variation in the probability of TD occurrence by means of generalized linear mixed models. The results revealed a significant interaction between the distance to the industrial complex and coverage of fruit trees at the microhabitat scale in explaining this probability (Adj. R2 = 22%; P = 0.001). This probability becomes higher than 0.50 when the distance from the industrial complex is more than 8 km and the cover of fruit trees is above 30%. A high probability of TD occurrence is also recorded in the presence of a very weak cover of urban areas. In the Gabès region, the highest probability of TD occurrence was recorded in the southern oases, thus highlighting their central role in conserving this Columbidae. For the species’ conservation, it is imperative to (i) uninstall the Gabès industrial complex from this coastal Mediterranean area, (ii) protect the southern oases, which constitute important breeding areas for the species in the south-east of Tunisia, (iii) enhance habitat quality in the farthest oases from the industrial complex, and (iv) set up a monitoring system aiming to quantify the impact of urban growth on this North African TD population.

STAT3 polymorphisms in North Africa and its implication in breast cancer.

BackgroundOnly 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.MethodsThe 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.ResultsThe 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.

Molecular Clocks and Archeogenomics of a Late Period Egyptian Date Palm Leaf Reveal Introgression from Wild Relatives and Add Timestamps on the Domestication.

The date palm, Phoenix dactylifera, has been a cornerstone of Middle Eastern and North African agriculture for millennia. It was first domesticated in the Persian Gulf, and its evolution appears to have been influenced by gene flow from two wild relatives, P. theophrasti, currently restricted to Crete and Turkey, and P. sylvestris, widespread from Bangladesh to the West Himalayas. Genomes of ancient date palm seeds show that gene flow from P. theophrasti to P. dactylifera may have occurred by ∼2,200 years ago, but traces of P. sylvestris could not be detected. We here integrate archeogenomics of a ∼2,100-year-old P. dactylifera leaf from Saqqara (Egypt), molecular-clock dating, and coalescence approaches with population genomic tests, to probe the hybridization between the date palm and its two closest relatives and provide minimum and maximum timestamps for its reticulated evolution. The Saqqara date palm shares a close genetic affinity with North African date palm populations, and we find clear genomic admixture from both P. theophrasti, and P. sylvestris, indicating that both had contributed to the date palm genome by 2,100 years ago. Molecular-clocks placed the divergence of P. theophrasti from P. dactylifera/P. sylvestris and that of P. dactylifera from P. sylvestris in the Upper Miocene, but strongly supported, conflicting topologies point to older gene flow between P. theophrasti and P. dactylifera, and P. sylvestris and P. dactylifera. Our work highlights the ancient hybrid origin of the date palms, and prompts the investigation of the functional significance of genetic material introgressed from both close relatives, which in turn could prove useful for modern date palm breeding.

Phylogeography of Aphanius fasciatus (Osteichthyes: Aphaniidae) in the Mediterranean Sea, with a focus on its conservation in Cyprus

Aphanius fasciatus is a small fish occurring in Mediterranean brackish environments. In Cyprus it is known from three localities separated by long stretches of coast. The genetic diversity of these populations was evaluated using fragments of two mitochondrial genes. A comparison with the other available data showed that Cyprus populations represent a distinct lineage. The other lineages are concentrated in a relatively small area between the Strait of Sicily and the Western Ionian Sea, while all other areas include a subset of these lineages, suggesting that the aforementioned area might have acted as a glacial refugium. Landlocked North-African populations diverge from all other populations, suggesting that they might have originated in the Late Pleistocene, during transgression events of the Mediterranean Sea in North-African inland water bodies. The genetic diversity of A. fasciatus varied across different Cyprus populations, with a pattern mirroring the degree of environmental degradation, which likely affected population genetic variability through demographic reductions. The three Cyprus populations showed genetic uniqueness, suggesting the need of population-based management practices; the low genetic diversity of two populations, and the number of threats affecting them, suggest that the species should be considered endangered at national level and deserves protection measures.

Breeding Ecology of the Iberian Chiffchaff Phylloscopus ibericus: First Data from North Africa

Till now, the breeding biology of several North African bird populations has been little studied, particularly that of the southern populations of Iberian chiffchaff Phylloscopus ibericus. In the present study, total of 31 nests of Iberian chiffchaff were monitored in the northeastern Algeria during 2013–2017. The nesting period, clutch and brood sizes, and reproductive success of the species were determined. The first egg-laying dates of the first broods were spread over the first twenty days of April. There were significant among-year variations in nesting seasons. The Iberian chiffchaff clutch sizes averaged 4.51 eggs. The number of hatchlings and fledglings averaged 4.09 and 3.54 nestlings, respectively. There is no correlation between the nest height above the ground and the hatching and the breeding success of the species. Predation and nest abandonment were the main causes of the breeding failure of the Iberian chiffchaff in studied population, however, in general the breeding success was high – 80.7%. Breeding data for the Iberian chiffchaff at the southern edge of its breeding range in North Africa show smaller clutches and production of fewer young compared to the common chiffchaff Phylloscopus collybita in Europe.

The genomes of ancient date palms germinated from 2,000 y old seeds

Seven date palm seeds (Phoenix dactylifera L.), radiocarbon dated from the fourth century BCE to the second century CE, were recovered from archaeological sites in the Southern Levant and germinated to yield viable plants. We conducted whole-genome sequencing of these germinated ancient samples and used single-nucleotide polymorphism data to examine the genetics of these previously extinct Judean date palms. We find that the oldest seeds from the fourth to first century BCE are related to modern West Asian date varieties, but later material from the second century BCE to second century CE showed increasing genetic affinities to present-day North African date palms. Population genomic analysis reveals that by ∼2,400 to 2,000 y ago, the P. dactylifera gene pool in the Eastern Mediterranean already contained introgressed segments from the Cretan palm Phoenix theophrasti, a crucial genetic feature of the modern North African date palm populations. The P. theophrasti introgression fraction content is generally higher in the later samples, while introgression tracts are longer in these ancient germinated date palms compared to modern North African varieties. These results provide insights into crop evolution arising from an analysis of plants originating from ancient germinated seeds and demonstrate what can be accomplished with the application of a resurrection genomics approach.

A Snapshot of Social Risk Factors and Associations with Health Outcomes in a Community Sample of Middle Eastern and North African (MENA) People in the U.S.

Social factors (e.g. housing, food security, etc.) contribute significantly to health. The purpose of this study is to describe social risk and social exclusion factors in one of the largest Middle Eastern and North African (MENA) populations in the U.S. and their association with health outcomes. We conducted a cross-sectional study with a community convenience sample of 412 adults who self-identify as MENA. Weighted, adjusted linear regression models were used to examine relationships of interest. Prevalent social risks included transportation barriers to healthcare (33%), food insecurity (33%), and financial strain (25%). In adjusted models, perception of being treated unfairly (Estimate (SE) 0.08 (0.04), p < 0.05) and fear of deportation (0.26 (0.06), p < 0.001) were associated with more social risk factors. More social risk factors were associated with worse self-reported health (0.09 (0.03), p < 0.01), more chronic conditions (0.11 (0.03), p < 0.004), and more mental health symptoms (0.34 (0.14) p < 0.01).Social risk is high among those perceiving unfairness and fear deportation. Those with more social risk factors reported worse health. These findings have implications for social needs screening and referral models that can best serve U.S. MENA sub-populations.

Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa.

Acephalic spermatozoa syndrome (ASS) is a rare but extremely severe type of teratozoospermia, defined by the presence of a majority of headless flagella and a minority of tail-less sperm heads in the ejaculate. Like the other severe monomorphic teratozoospermias, ASS has a strong genetic basis and is most often caused by bi-allelic variants in SUN5 (Sad1 and UNC84 domain-containing 5). Using whole exome sequencing (WES), we investigated a cohort of nine infertile subjects displaying ASS. These subjects were recruited in three centers located in France and Tunisia, but all originated from North Africa. Sperm from subjects carrying candidate genetic variants were subjected to immunofluorescence analysis and transmission electron microscopy. Moreover, fluorescent in situ hybridization (FISH) was performed on sperm nuclei to assess their chromosomal content. Variant filtering permitted us to identify the same SUN5 homozygous frameshift variant (c.211+1_211+2dup) in 7/9 individuals (78%). SUN5 encodes a protein localized on the posterior part of the nuclear envelope that is necessary for the attachment of the tail to the sperm head. Immunofluorescence assays performed on sperm cells from three mutated subjects revealed a total absence of SUN5, thus demonstrating the deleterious impact of the identified variant on protein expression. Transmission electron microscopy showed a conserved flagellar structure and a slightly decondensed chromatin. FISH did not highlight a higher rate of chromosome aneuploidy in spermatozoa from SUN5 patients compared to controls, indicating that intra-cytoplasmic sperm injection (ICSI) can be proposed for patients carrying the c.211+1_211+2dup variant. These results suggest that the identified SUN5 variant is the main cause of ASS in the North African population. Consequently, a simple and inexpensive genotyping of the 211+1_211+2dup variant could be beneficial for affected men of North African origin before resorting to more exhaustive genetic analyses.

Isotopic reconstruction of diet at the Vandalic period (ca. 5th–6th centuries AD) Theodosian Wall cemetery at Carthage, Tunisia

AbstractHere we present the first isotopic investigation of a Vandalic period site (ca. 5th–6th centuries AD), the Theodosian Wall cemetery at Carthage, in modern day Tunis, Tunisia. The focus of this research is to determine the general diet and food consumption patterns of this population during this important and pivotal period of antiquity in North Africa. To this end, collagen stable isotope ratios (δ13C, δ15N) are reported for a variety of fauna (n = 20) and humans (n = 70). The human mean±SD results (δ13C = −19.3 ± 0.4‰; δ15N = 10.7 ± 1.4‰) reflect a diet that was based predominantly on C3 terrestrial plants with varying amounts of animal protein from domestic animals such as sheep/goats, cows, and pigs. No statistically significant isotopic differences between males and females, developmental age, or time period of burial were found. The isotopic results from the Theodosian Wall cemetery at Carthage are compared to eight previously published Roman and Early Byzantine sites from the Mediterranean region (Carrer Ample 1, Joan Planells, S'Hort des Llimoners (Spain); Isola Sacra, Velia, Herculaneum (Italy); Ephesus (Turkey); and Leptiminus (Tunisia)). The lack of significant amounts of marine foods in the diets of the Vandal era population at Carthage is in stark contrast to the Roman inhabitants of Leptiminus, where significant consumption of marine‐derived dietary resources was found. As Leptiminus is ~180 km southeast of Carthage, the work presented here shows that large dietary differences existed in North African populations during antiquity.

SLC22A4 Gene in Hereditary Non-syndromic Hearing Loss: Recurrence and Incomplete Penetrance of the p.C113Y Mutation in Northwest Africa.

Inherited hearing loss is extremely heterogeneous both clinically and genetically. In addition, the spectrum of deafness-causing genetic variants differs greatly among geographical areas and ethnicities. The identification of the causal mutation in affected families allows early diagnosis, clinical follow-up, and genetic counseling. A large consanguineous family of Moroccan origin affected by autosomal recessive sensorineural hearing loss (ARSNHL) was subjected to genome-wide linkage analysis and exome sequencing. Exome-wide variant analysis and prioritization identified the SLC22A4 p.C113Y missense variant (rs768484124) as the most likely cause of ARSNHL in the family, falling within the unique significant (LOD score>3) linkage region on chromosome 5. Indeed, the same variant was previously reported in two Tunisian ARSNHL pedigrees. The variant is present in the homozygous state in all six affected individuals, but also in one normal-hearing sibling, suggesting incomplete penetrance. The mutation is absent in about 1,000 individuals from the Greater Middle East Variome study cohort, including individuals from the North African population, as well as in an additional seven deaf patients from the same geographical area, recruited and screened for mutations in the SLC22A4 gene. This study represents the first independent replication of the involvement of SLC22A4 in ARSNHL, highlighting the importance of the gene, and of the p.C113Y mutation, at least in the Northwest African population.

Genetic diversity of the North African population revealed by the typing of SNPs in the DRD2/ANKK1 genomic region.

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.