Linking between genetic structure and geographical distance: Study of the maternal gene pool in the Ethiopian population

Background The correlation between genetics and geographical distance has already been examined through the study of the dispersion of human populations, especially in terms of uniparental genetic markers.

Aim The present work characterises, at the level of the mitochondrial DNA (mtDNA), two new samples of Amhara and Oromo populations from Ethiopia to evaluate the possible pattern of distribution for mtDNA variation and to test the hypothesis of the Isolation-by-Distance (IBD) model among African, European and Middle-Eastern populations.

Subjects and methods This study analysed 173 individuals belonging to two ethnic groups of Ethiopia, Amhara and Oromo, by assaying HVS-I and HVS-II of mtDNA D-loop and informative coding region SNPs of mtDNA.

Results The analysis suggests a relationship between genetic and geographic distances, affirming that the mtDNA pool of Africa, Europe and the Middle East might be coherent with the IBD model. Moreover, the mtDNA gene pools of the Sub-Saharan African and Mediterranean populations were very different.

Conclusion In this study the pattern of mtDNA distribution, beginning with the Ethiopian plateau, was tested in the IBD model. It could be affirmed that, on a continent scale, the mtDNA pool of Africa, Europe and the Middle East might fall under the IBD model.     

Alu insertion polymorphisms in the African Sahel and the origin of Fulani pastoralists

Background: The origin of Western African pastoralism, represented today by the Fulani nomads, has been a highly debated issue for the past decades, and has not yet been conclusively resolved.

Aim: This study focused on Alu polymorphisms in sedentary and nomadic populations across the African Sahel to investigate patterns of diversity that can complement the existing results and contribute to resolving issues concerning the origin of West African pastoralism.

Subjects and methods: A new dataset of 21 Alu biallelic markers covering a substantial part of the African Sahel has been analysed jointly with several published North African populations.

Results: Interestingly, with regard to Alu variation, the relationship of Fulani pastoralists to North Africans is not as evident as was earlier revealed by studies of uniparental loci such as mtDNA and NRY. Alu insertions point rather to an affinity of Fulani pastoralists to Eastern Africans also leading a pastoral lifestyle.

Conclusions: It is suggested that contemporary Fulani pastoralists might be descendants of an ancestral Eastern African population that, while crossing the Sahara in the Holocene, admixed slightly with a population of Eurasian (as evidenced by uniparental polymorphisms) ancestry. It seems that, in the Fulani pastoralists, Alu elements reflect more ancient genetic relationships than do uniparental genetic systems.     

An investigation of the genetic diversity of the Kerkennah islands and Mahdia (Tunisia) using biparental markers

Background: Kerkennah is one of the main inhabited islands of Tunisia. The origin of the population of Kerkennah has not been established and no well-defined ethnic groups have been identified nor are genetic studies available. Mahdia, a Tunisian coastal city, has a long history dating back to ancient times.

Aim: To discover the genetic diversity of the two studied populations and analyse their relationships with other Mediterranean populations.

Subject and methods: Seven human-specific Alu insertion polymorphisms were typed in 99 individuals born in Kerkennah and Mahdia.

Results: A neighbour-joining tree and MDS multidimensional scaling analysis showed that these Tunisian populations are scattered amongst North African and Europeans populations, indicating their high genetic diversity and mosaic aspect. The important finding of this study was the proximity of Kerkennah to Moroccans. Hence, the actual gene pool of this insular population may descend from the ancestral population known to be of Moroccan origin. Concerning Mahdia, its closeness to Eurasian populations and some Tunisian groups reflected a high Eurasian genetic component for North African populations and confirmed their heterogeneity.

Conclusion: The strategic location of the two studied populations and their fortifications have allowed them to play a leading role in the Mediterranean basin.     

Y-Chromosome haplotypes reveal relationships between populations of the Arabian Peninsula,North Africa and South Asia

Background: The United Arab Emirates (UAE) is positioned at the crossroads of human migration out of Africa and through to Asia and Europe.

Aim: To compare the degree of genetic diversity of the Arabian UAE population with populations in other countries from the Middle East, South Asia and North Africa.

Subjects and methods: Twenty-seven Y-STR were analysed in 217 individuals. Y-STR haplotypes from this study were compared to population data stored in YHRD, using MDS and AMOVA.

Results: Two hundred and twelve haplotypes were observed in the 217 individuals studied. Although the reduction in Y-STR loci from 27 to 17 resulted in a decrease in discriminatory power, comparisons of populations were possible. The UAE population clustered closer with other populations of the Middle East. The South Asian and North African populations were separated by Middle Eastern populations in between both clusters.

Conclusion: This is the first study to report the diversity of a population of the Arabian Peninsula using 27 Y-STR. MDS plots show that Middle Eastern populations are positioned in the centre, with African, Asian and European populations around the Arab population cluster. The findings of this study are consistent with this region being at the epicentre of human migration between continents.     

The timing of mandibular tooth formation in two African groups

Background: Ethnic differences in the timing of human tooth development are unclear.

Aim: To describe similarities and differences in the timing of tooth formation in two groups of Sudanese children and young adults.

Subjects and methods: The sample consisted of healthy individuals from Khartoum, Sudan, aged 2–23 years. The Northern group was of Arab origin (848 males, 802 females) and the Western group was of African origin (846 males, 402 females). Each mandibular left permanent tooth from first incisor to third molar was assessed from dental radiographs into one of 15 development stages. Mean ages at entry for 306 tooth stages were calculated using probit regression in males/females in each group and compared using a t-test.

Results: Mean ages were not significantly different in most tooth stage comparisons between ethnic groups for both males (61/75) and females (56/76), despite a tendency of earlier mean ages in the Western group. Mean ages for most tooth stage comparisons between males and females (137/155) were not significantly different within ethnic groups suggesting low sexual dimorphism.

Conclusion: The mean ages of most mandibular tooth formation stages were generally not significantly different between ethnic groups or between males and females in this study.     

Allergen immunotherapy in allergic rhinitis: current use and future trends

Introduction: Type-1 allergies are among the most chronic common diseases of humans. Allergen immunotherapy (AIT) is the only causative and disease-modifying treatment option besides allergen avoidance. Severe systemic adverse allergic reactions may be induced by every AIT treatment. Different approaches have been used to provide safer AIT preparations to lower or even totally overcome this risk.

Areas covered: A structured literature recherche in Medline and Pubmed under inclusion of national and international guidelines and Cochrane meta-analyses has been performed aiming at reviewing clinical use of such approaches in AIT.

New allergen preparations may include allergoids, recombinant allergens (recA) and modified recombinant allergens (recA) in subcutaneous as well as in mucosal immunotherapies (application e.g. using bronchial, nasal, oral and sublingual application) with sublingual being the established mucosal application route and new ways of application like intralymphatic and epicutaneous immunotherapy.

Expert commentary: Immune-modifying agents like Virus-like particles and CpG-motifs, adjuvants like MPL and aluminum hydroxide are evaluated and found to increase and direct the immunological response toward immunological tolerance.

New forms of allergen extracts can improve safety and efficacy of AIT and may change our way of performing allergen immunotherapy in the future.     

Ethnic composition and genetic differentiation of the Libyan population: insights on Alu polymorphisms

Background: It is thought that the ancient population of Libya was mainly composed of Saharan Berbers. Socio-geographic conditions and historical events have exerted some changes on the composition of the present-day Libyan population.

Aim: To screen a set of autosomal Alu markers in a representative sample of the general Libyan population in order to study its ethnic and genetic structure and to re-examine its genetic relationships with Mediterranean and Middle Eastern groups.

Subjects and methods: A sample of 190 Libyans was analysed for 17 Alu insertions. The sample was divided according to the Arabic or Berber origin of individuals’ surnames.

Results: The current general Libyan population is homogeneous and shows considerable genetic diversity compared with other North Mediterranean and North African populations. It shows intermediate genetic distances between Moroccans, Algerians and Tunisians on one side and Egyptian Siwa Berbers on the other. No particular affinities with Middle Eastern groups were detected.

Conclusion: Alu insertions are useful markers to contribute to the reconstruction of human population history at a microgeographic scale, in particular when the analyses include anthropologically well sampled populations. The present results provide new information to improve understanding some aspects of the complex peopling of North Africa.     

Geographical and social influences on genetic diversity within the Egyptian population: analyses of Alu insertion polymorphisms

Background: The geographical location of Egypt at the crossroads of several major cultural areas between North Africa and the Middle East has contributed to its population history.

Aim: To analyse the genetic structure of the population living in two geographical parts of Egypt.

Subjects and methods: A sample of 112 Egyptians from the North African part of Egypt (Ismailia sample) and a sample of 52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion polymorphisms.

Results: The results of the present study showed a significant genetic difference between the Sinai and Ismailia samples. The latter showed an evident genetic affinity with North African populations; whereas the Sinai sample was found to be genetically closer to the Middle East populations. The Sinai sample showed a low average heterozygosity, unlike that found in the Ismailia sample.

Conclusion: This study provides new insights into the genetic structure of the Egyptian population living in a land bridge between Africa and Asia. Results suggest a genetic discontinuity between the Sinai population and that of the North African part of Egypt. This discontinuity would have been maintained thanks to geo-climatic and social factors.     

Pregnane X Receptor Polymorphisms and Risk of Inflammatory Bowel Disease: A Meta-Analysis

Background: Pregnane X receptor (PXR) gene polymorphisms have been widely studied in terms of the association with inflammatory bowel disease (IBD), with inconsistent results.

Objective: The present meta-analysis was performed to assess the association between PXR gene polymorphisms and the susceptibility of IBD, Crohn’s disease (CD), and ulcerative colitis (UC).

Methods: PubMed, Wanfang, and CNKI databases were searched for eligible studies before November 1, 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to calculate the various genetic models using either a fixed-effect or a random-effect model. The heterogeneity of the included studies was examined with Cochran Q and I² statistics. Begg’s rank correlation test and Egger’s linear regression test were used to assess the publication bias.

Results: A total of six studies with 4248 cases and 3853 controls were included in this meta-analysis. Three PXR gene polymorphisms were evaluated: rs1523127, rs2276707, and rs6785049. Our analyses of rs1523127, rs2276707, and rs6785049 suggested that PXR gene polymorphism had no obvious influence on the risk of IBD in Caucasians. Subgroup analyses based on disease type showed similar results.

Conclusion: Our meta-analysis revealed that PXR gene polymorphism may not be significantly associated with IBD susceptibility. However, the number of original studies was limited and further studies with large samples are needed to verify the results.

Abbreviations: PXR = pregnane X receptor, IBD = inflammatory bowel disease, CD = Crohn’s disease, UC = ulcerative colitis, ORs = pooled odds ratios, 95% CIs = 95% confidence intervals, NOS = Newcastle–Ottawa scale, HWE = Hardy–Weinberg equilibrium.     

Clinical and immunological studies for 105 Japanese seropositive patients of epidermolysis bullosa acquisita examined at Kurume University

Objectives: Using our serological diagnostic criteria, we selected 105 Japanese patients with epidermolysis bullosa acquisita (EBA), an autoimmune bullous disease (AIBD) reacting with type VII collagen, from our cohort of 5063 AIBD patients.

Methods: We examined the patients clinically and immunologically.

Results: We found diversity of clinical manifestations in both cutaneous and oral mucosal lesions and a high rate of inflammatory-type EBA patients in Japan. Common treatments were systemic steroids, followed by immunosuppressives, DDS, tetracycline/minocycline and colchicine. Immunological studies revealed that indirect immunofluorescence of 1M-NaCl-split skin, immunoblotting of dermal extract, and type VII collagen ELISA were sensitive methods, with possible multiplicity of circulating autoantibodies against other basement membrane autoantigens.

Conclusion: The present study analyzed the largest cohort of EBA patients, confirming the scarcity of EBA (only 105 of the 5063 AIBD patients), and showed that the three serological tests are useful for the diagnosis of EBA.     

Unusual sleep experiences and dissociation as mediators between sleep quality and proneness to hallucinations in a nonclinical population sample: a preliminary study

Introduction: The purpose of this study was to examine the relationship of sleep quality to proneness to hallucinations and the mediating role of dissociation and unusual sleep experiences in a nonclinical sample.

Methods: One hundred and seventy-seven participants completed a questionnaire on sleep quality, a dissociative experiences scale, an unusual sleep experiences scale and a hallucination proneness scale.

Results: The results showed a significant positive association between quality of sleep and hallucination proneness, dissociation and unusual sleep experiences, and that dissociation and unusual sleep experiences fully mediated between sleep quality and hallucination proneness.

Conclusions: Our study highlights the importance of variables related to sleep quality and unusual sleep experiences and dissociation in understanding hallucinations, and the importance of taking these variables into consideration in designing intervention directed at reducing distress caused by hallucinations.     

The effect of preexisting anti-carrier immunity on subsequent responses to CRM197 or Qb-VLP conjugate vaccines

Context: Certain antigens, such as haptens (small molecules), short peptides, and carbohydrates (e.g. bacterial polysaccharides) are non- or poorly immunogenic unless conjugated to a carrier molecule that provides a structural scaffold for antigen presentation as well as T cell help required for B-cell activation and maturation. However, the carriers themselves are immunogenic and resulting carrier-specific immune responses may impact the immunogenicity of other conjugate vaccines using the same carrier that are administered subsequently.

Objective: Herein, using two different carriers (cross-reactive material 197, CRM and Qb-VLP), we examined in mice the impact that preexisting anti-carrier antibodies (Ab) had on subsequent immune responses to conjugates with either the same or a different carrier.

Method: For this purpose, we used two nicotine hapten conjugates (NIC7-CRM or NIC-Qb), two IgE peptide conjugates (Y-CRM or Y-Qb), and a pneumococcal polysaccharide conjugate (Prevnar 13^®).

Results: Prior exposure to CRM or Qb-VLP significantly reduced subsequent responses to the conjugated antigen having the homologous carrier, with the exception of Prevnar 13® where anti-polysaccharide responses were similar to those in animals without preexisting anti-carrier Ab.

Conclusion: Collectively, the data suggest that the relative sizes of the antigen and carrier, as well as the conjugation density for a given conjugate impact the extent of anti-carrier suppression. All animals developed anti-carrier responses with repeat vaccination and the differences in Ab titer between groups with and without preexisting anti-carrier responses became less apparent; however, anti-carrier effects were more durable for Ab function.     

Enhancement of NK cells proliferation and function by Shikonin

Context: Shikonin is a kind of naphthoquinone compound found mainly in Lithospermum erythrorhizon Sieb,et Zucc. Previous studies have shown that Shikonin has anti-tumor, anti-inflammatory and extensive pharmacological effects. According to new studies, Shikonin could also modulate the immune system function, but the effect to NK (nature killer) cells is yet unknown.

Objective: To investigate the effect and mechanism of Shikonin on NK cells proliferation and cytotoxicity to colon cancer cell line (Caco-2).

Methods: The proliferation and cytotoxicity of NK cells cultured with Shikonin were detected with CCK-8 assay. The expressions of perforin, GranB and IFN-γ were examined with FCM. The content of TNF-alpha was disclosed with ELISA kit. p-ERK1/2 and p-Akt expression of NK cells were detected with western blot.

Results: With CCK-8 assay, it is found that Shikonin could significantly enhance NK cells proliferation and cytotoxicity to colon cancer cells. With FCM assay, it is found that Shikonin could improve the expression of perforin and GranB in a dose-dependent manner. Shikonin had no effect on TNF-alpha and IFN-γ expression. In mechanism, the study shows that Shikonin could enhance the expression of p-ERK1/2 and p-Akt.

Conclusions: Shikonin enhances NK cells proliferation and cytotoxicity via the improvement of perforin, GranB, p-ERK1/2 and p-Akt expression.     

Body parameters of Czech breastfed children compared to the Czech references and WHO growth standards

Background: The study concerns the comparison of percentile curves of Czech breastfed children with Czech national references from 1991 and 2001 and WHO growth standards. Growth charts of breastfed children demonstrate different curve shapes, especially in the first months of life. Incorrect interpretation of the growth curve could lead to premature introduction of complementary foods or infant formula.

Aim: The comparison of four body parameters of Czech breastfed children with currently used Czech national references and WHO standards in order to recommend that Czech paediatricians use either Czech references or WHO standards in their practice.

Subjects and methods: Nine hundred and sixty breastfed children were included in the study of length-for-age, head circumference-for-age, weight-for-age and weight-for-length parameters. All percentile curves were compared. Values of the 50th percentile expressed in z-scores based on both Czech references and WHO standards were tested.

Results: The study confirmed results of previous surveys documenting that growth of breastfed children is specific. Nevertheless, percentile curves of growth parameters of Czech breastfed children are closer to Czech references than WHO standards.

Conclusions: The Czech national references fulfil the needs of Czech paediatricians (with pointing to specifics of breastfed child growth) and WHO standards are suitable, especially for international comparison.     

PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus

Background: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease.

Objective: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene.

Methods: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene.

Results: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs.

Conclusions: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.     

Evaluation of the genetic parameters for 10 common and five new ESS core autosomal STR loci in seven major geographic regions and the largest metropolitan province of Turkey

Background: Situated at the crossroads of Asia, Middle East and Europe, Turkey has an ethnically diverse population of over 78 milllion people.

Aim: To investigate the population genetics and potential differences in the autosomal short tandem repeat (STR) polymorphisms across all the major geographic regions and largest metropolitan province of Turkey within the context of the Near Eastern/European genetic landscape.

Subjects and methods: Samples from a total of 5299 unrelated individuals were analysed at 10 common [D2S1338, D3S1358, D8S1179, D16S539, D18S51, D19S433, D21S11, FGA, TH01, vWA] and five new European Standard Set (ESS) core autosomal STR loci [D1S1656, D2S441, D10S1248, D12S391, D22S1045].

Results: Allele frequencies, statistical parameters of forensic interest and population differentiation tests were calculated for nine population datasets corresponding to the seven major geographic regions, the largest metropolitan province, and a combined dataset for the entire country. Cumulative results confirmed the presence of significant differences among these nine autosomal datasets themselves and with those from the nearby populations, therefore justifying the differential use of these separate datasets on a case-by-case basis in forensic investigations.

Conclusion: This collection of autosomal STR population datasets comprises the largest and most comprehensive of its kind from Turkey so far.     

Systematic overview of neuroanatomical differences in ADHD: Definitive evidence

Objectives: This article seeks to identify neuroanatomical differences in ADHD through an overview of systematic reviews that report encephalic differences compared to a control group in volume, area, activation likelihood or chemical composition.

Methods: We conducted a systematic search using Cochrane guidelines and PRISMA criteria in PubMed, Scopus, Web of Science, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects.

Results: Results revealed broad encephalic involvement that includes a functional frontal and cingulate hypoactivation and structural differences in corpus callosum, cerebellum and basal nuclei.

Conclusions: ADHD symptoms might be due to a multi-network unbalanced functioning hypothesis.