The sickle gene polymorphism in North Africa

Abstract Analysis of the restriction endonuclease Hpa 1-beta globin gene linkage has been performed in a predominantly Arab population of North Africa possessing the sickle (beta A) gene is found associated with a 7.6 kilobase) or 7.0 kb Hpa 1 fragment (54/54 assignable beta A genes), whereas the beta S gene is found associated with a 13 kb Hpa 1 fragment (42/42 assignable beta S genes). The results demonstrate a very tight linkage of the beta S gene to the 13 kb Hpa 1 fragment as well as a very low probability that a beta A gene will be found on a 13 kb Hpa 1 fragment. Thus, the North African population presents a nearly ideal opportunity for prenatal diagnosis solely by Hpa 1-beta globin gene linkage analysis. Additionally, the evidence supports the hypothesis that the beta S gene flowed from West Africa rather than from Arab populations in the Middle East.

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The sickle gene polymorphism in North Africa

Blood ◽

10.1182/blood.v58.3.599.bloodjournal583599 ◽

1981 ◽

Vol 58 (3) ◽

pp. 599-601

Author(s):

JG Mears ◽

C Beldjord ◽

M Benabadji ◽

Ya Belghiti ◽

MA Baddou ◽

...

Keyword(s):

North Africa ◽

Globin Gene ◽

Beta Globin ◽

North African ◽

Arab Population ◽

Beta Globin Gene ◽

Gene Linkage ◽

S Gene ◽

The North ◽

North African Population

Analysis of the restriction endonuclease Hpa 1-beta globin gene linkage has been performed in a predominantly Arab population of North Africa possessing the sickle (beta A) gene is found associated with a 7.6 kilobase) or 7.0 kb Hpa 1 fragment (54/54 assignable beta A genes), whereas the beta S gene is found associated with a 13 kb Hpa 1 fragment (42/42 assignable beta S genes). The results demonstrate a very tight linkage of the beta S gene to the 13 kb Hpa 1 fragment as well as a very low probability that a beta A gene will be found on a 13 kb Hpa 1 fragment. Thus, the North African population presents a nearly ideal opportunity for prenatal diagnosis solely by Hpa 1-beta globin gene linkage analysis. Additionally, the evidence supports the hypothesis that the beta S gene flowed from West Africa rather than from Arab populations in the Middle East.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22042187 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2187

Author(s):

Caroline Cazin ◽

Yasmine Boumerdassi ◽

Guillaume Martinez ◽

Selima Fourati Ben Mustapha ◽

Marjorie Whitfield ◽

...

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

North Africa ◽

Posterior Part ◽

North African ◽

The North ◽

Transmission Electron ◽

Variant Filtering ◽

North African Population ◽

Sperm Nuclei

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.

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Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease

Eastern Mediterranean Health Journal ◽

10.26719/1999.5.6.1154 ◽

1999 ◽

Vol 5 (6) ◽

pp. 1254-1258

Author(s):

M. A. El Hazmi ◽

A. S. Warsy ◽

N. Bashir ◽

A. Beshlawi ◽

I. R. Hussain

Keyword(s):

Saudi Arabia ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Presentation ◽

Globin Gene ◽

Beta Globin ◽

Cell Disease ◽

Beta Globin Gene ◽

The North ◽

Cell Gene

Wecollaborated with researchers from Egypt, Syrian Arab Republic and Jordan in a study of patients with sickle-cell disease from those countries, and from various parts of Saudi Arabia, in order to investigate the influence of genetics on the clinical presentation of the disease, and to attempt to determine the origin of the sickle-cell gene in Arabs. Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there are at least two major foci for the origin of the sickle-cell gene, one in the eastern part of Saudi Arabia, and the other in the populations of North Africa and the north-western part of the Arabian peninsula

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Insights into the Middle Eastern paternal genetic pool in Tunisia: high prevalence of T-M70 haplogroup in an Arab population

Scientific Reports ◽

10.1038/s41598-021-95144-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sarra Elkamel ◽

Sofia L. Marques ◽

Luis Alvarez ◽

Veronica Gomes ◽

Sami Boussetta ◽

...

Keyword(s):

North Africa ◽

Middle Eastern ◽

North African ◽

Arab Population ◽

The North ◽

High Prevalence ◽

Sub Saharan ◽

Genetic Pool ◽

Spread Of Agriculture ◽

Two Populations

AbstractTo obtain refreshed insights into the paternal lineages of Tunisian populations, Y-chromosome diversity was assessed in two populations belonging to an Arab genealogical lineage, Kairouan and Wesletia, as well as in four Tunisian Andalusian populations, Testour, Slouguia, Qalaat-El-Andalous and El Alia. The Arabs from Kairouan revealed 73.47% of E-M81 and close affinities with Berber groups, indicating they are likely arabized Berbers, clearly differentiated from the Arabs from Wesletia, who harbored the highest frequency (71.8%) of the Middle Eastern component ever observed in North Africa. In the Tunisian Andalusians, the North African component largely prevailed, followed by the Middle Eastern contribution. Global comparative analysis highlighted the heterogeneity of Tunisian populations, among which, as a whole, dominated a set of lineages ascribed to be of autochthonous Berber origin (71.67%), beside a component of essentially Middle Eastern extraction (18.35%), and signatures of Sub-Saharan (5.2%), European (3.45%) and Asiatic (1.33%) contributions. The remarkable frequency of T-M70 in Wesletia (17.4%) prompted to refine its phylogeographic analysis, allowing to confirm its Middle Eastern origin, though signs of local evolution in Northern Africa were also detected. Evidence was clear on the ancient introduction of T lineages into the region, probably since Neolithic times associated to spread of agriculture.

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Structurally diverse molecular deletions in the beta-globin gene cluster exhibit an identical phenotype on interaction with the beta S- gene

Blood ◽

10.1182/blood.v65.5.1245.1245 ◽

1985 ◽

Vol 65 (5) ◽

pp. 1245-1251 ◽

Cited By ~ 13

Author(s):

NP Anagnou ◽

T Papayannopoulou ◽

G Stamatoyannopoulos ◽

AW Nienhuis

Keyword(s):

Globin Gene ◽

Clinical Syndrome ◽

Beta Thalassemia ◽

Complete Suppression ◽

Beta Globin ◽

Erythroid Progenitors ◽

Hemoglobin F ◽

Fetal Sheep ◽

Beta Globin Gene ◽

S Gene

Abstract We have characterized a new deletion that increases hemoglobin F synthesis in an American black woman who is doubly heterozygous for this mutation and the beta S-gene. The 5 ' endpoint is 2.4 +/- 0.1 kilobases (kb) upstream from the delta-globin gene, and the 3′ endpoint is 0.2 +/- 0.1 kb downstream from the beta-globin gene; the deletion is 12 kb long. Both members of the Alu moderately repetitive DNA sequence family, normally present upstream from the delta-globin gene, are preserved. The patient is asymptomatic with a mild anemia and 24.8% HbF. The patient's husband and daughter have a similar clinical syndrome, with HbF levels of 22.4% and 25.4%, respectively. Both husband and daughter are doubly heterozygous for the beta S-gene and the Ghana type of hereditary persistence of fetal hemoglobin (HPFH) deletion (HPFH-2). The 5′ end of this deletion is in the psi beta-gene, and its total length is more than 70 kb. All three members of the family have normocytic red cells, of which 95% or more are F cells as detected by immunofluorescence. Previous studies have shown that culture of the erythroid progenitors (BFU-E) from both types of these compound heterozygotes in the presence of fetal sheep serum, rich in 'switching factor,” resulted in complete suppression of HbF synthesis. Although the newly described deletion resembles the Sicilian type of delta beta-thalassemia by its size and preservation of the Alu sequences, the clinical and biological phenotype produced by its interaction with the beta S-gene is very similar to that of the HPFH- type deletion.

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Structurally diverse molecular deletions in the beta-globin gene cluster exhibit an identical phenotype on interaction with the beta S- gene

Blood ◽

10.1182/blood.v65.5.1245.bloodjournal6551245 ◽

1985 ◽

Vol 65 (5) ◽

pp. 1245-1251 ◽

Cited By ~ 1

Author(s):

NP Anagnou ◽

T Papayannopoulou ◽

G Stamatoyannopoulos ◽

AW Nienhuis

Keyword(s):

Globin Gene ◽

Clinical Syndrome ◽

Beta Thalassemia ◽

Complete Suppression ◽

Beta Globin ◽

Erythroid Progenitors ◽

Hemoglobin F ◽

Fetal Sheep ◽

Beta Globin Gene ◽

S Gene

We have characterized a new deletion that increases hemoglobin F synthesis in an American black woman who is doubly heterozygous for this mutation and the beta S-gene. The 5 ' endpoint is 2.4 +/- 0.1 kilobases (kb) upstream from the delta-globin gene, and the 3′ endpoint is 0.2 +/- 0.1 kb downstream from the beta-globin gene; the deletion is 12 kb long. Both members of the Alu moderately repetitive DNA sequence family, normally present upstream from the delta-globin gene, are preserved. The patient is asymptomatic with a mild anemia and 24.8% HbF. The patient's husband and daughter have a similar clinical syndrome, with HbF levels of 22.4% and 25.4%, respectively. Both husband and daughter are doubly heterozygous for the beta S-gene and the Ghana type of hereditary persistence of fetal hemoglobin (HPFH) deletion (HPFH-2). The 5′ end of this deletion is in the psi beta-gene, and its total length is more than 70 kb. All three members of the family have normocytic red cells, of which 95% or more are F cells as detected by immunofluorescence. Previous studies have shown that culture of the erythroid progenitors (BFU-E) from both types of these compound heterozygotes in the presence of fetal sheep serum, rich in 'switching factor,” resulted in complete suppression of HbF synthesis. Although the newly described deletion resembles the Sicilian type of delta beta-thalassemia by its size and preservation of the Alu sequences, the clinical and biological phenotype produced by its interaction with the beta S-gene is very similar to that of the HPFH- type deletion.

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