Hemoglobin electrophoresis and hemoglobinopathies in Kuwait.
TL;DR: The results of hemoglobin electrophoresis in the routine laboratory of a tertiary hospital in Kuwait indicated the need to streamline requests for the test, and the most commonly identified hemoglobinopathies were β-thalassemia minor, sickle cell trait, and Sβ+thal.
Abstract: Objectives: To analyze the results of hemoglobin electrophoresis (HE) in the routine laboratory of a tertiary hospital in Kuwait and to review the common types of hemoglobinopathies
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TL;DR: The frequency, distribution, clinical feature, management and prevention as well as gene interactions of the HbS genes with other haemoglobin disorders in the Middle Eastern Arab countries are outlined.
Abstract: The sickle cell (HbS) gene occurs at a variable frequency in the Middle Eastern Arab countries, with characteristic distribution patterns and representing an overall picture of blood genetic disorders in the region. The origin of the gene has been debated, but studies using β-globin gene haplotypes have ascertained that there were multiple origins for HbS. In some regions the HbS gene is common and exhibits polymorphism, while the reverse is true in others. A common causative factor for the high prevalence and maintenance of HbS and thalassaemia genes is malaria endemicity. The HbS gene also co-exists with other haemoglobin variants and thalassaemia genes and the resulting clinical state is referred to as sickle cell disease (SCD). In the Middle Eastern Arab countries, the clinical picture of SCD expresses two distinct forms, the benign and the severe forms, which are related to two distinct β-globin gene haplotypes. These are referred to as the Saudi-Indian and the Benin haplotypes, respectively. In a majority of the Middle Eastern Arab countries the HbS is linked to the Saudi-Indian haplotype, while in others it is linked to the Benin haplotype. This review outlines the frequency, distribution, clinical feature, management and prevention as well as gene interactions of the HbS genes with other haemoglobin disorders in the Middle Eastern Arab countries.
110 citations
TL;DR: The first genome resource imperative for designing future genetic studies in Saudi Arabian tribe subgroup is presented and a set of 2,485 SNPs show significantly different allele frequencies when compared to populations from other continents.
Abstract: Population of the State of Kuwait is composed of three genetic subgroups of inferred Persian, Saudi Arabian tribe and Bedouin ancestry. The Saudi Arabian tribe subgroup traces its origin to the Najd region of Saudi Arabia. By sequencing two whole genomes and thirteen exomes from this subgroup at high coverage (>40X), we identify 4,950,724 Single Nucleotide Polymorphisms (SNPs), 515,802 indels and 39,762 structural variations. Of the identified variants, 10,098 (8.3%) exomic SNPs, 139,923 (2.9%) non-exomic SNPs, 5,256 (54.3%) exomic indels, and 374,959 (74.08%) non-exomic indels are ‘novel’. Up to 8,070 (79.9%) of the reported novel biallelic exomic SNPs are seen in low frequency (minor allele frequency T] from CYP4F2 gene [MIM:*604426]) associated with warfarin dosage levels [MIM:#122700] required to elicit normal anticoagulant response; and a 3′ UTR SNP (rs6151429 [22:g.51063477T>C]) from ARSA gene [MIM:*607574]) associated with Metachromatic Leukodystrophy [MIM:#250100]. Hemoglobin Riyadh variant (identified for the first time in a Saudi Arabian woman) is observed in the exome data. The mitochondrial haplogroup profiles of the 15 individuals are consistent with the haplogroup diversity seen in Saudi Arabian natives, who are believed to have received substantial gene flow from Africa and eastern provenance. We present the first genome resource imperative for designing future genetic studies in Saudi Arabian tribe subgroup. The full-length genome sequences and the identified variants are available at ftp://dgr.dasmaninstitute.org and http://dgr.dasmaninstitute.org/DGR/gb.html.
40 citations
Cites background from "Hemoglobin electrophoresis and hemo..."
...[83] conducted a comprehensive electrophoretic screening of the Kuwaiti population and showed that 23....
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TL;DR: The resource provides a starting point for designing large-scale genetic studies in Peninsula including Kuwait, and Persian population and positions the sequenced genome between Asian and European genomes in congruence with geographical location of the region.
Abstract: The 1000 Genome project paved the way for sequencing diverse human populations. New genome projects are being established to sequence underrepresented populations helping in understanding human genetic diversity. The Kuwait Genome Project an initiative to sequence individual genomes from the three subgroups of Kuwaiti population namely, Saudi Arabian tribe; “tent-dwelling” Bedouin; and Persian, attributing their ancestry to different regions in Arabian Peninsula and to modern-day Iran (West Asia). These subgroups were in line with settlement history and are confirmed by genetic studies. In this work, we report whole genome sequence of a Kuwaiti native from Persian subgroup at >37X coverage. We document 3,573,824 SNPs, 404,090 insertions/deletions, and 11,138 structural variations. Out of the reported SNPs and indels, 85,939 are novel. We identify 295 ‘loss-of-function’ and 2,314 ’deleterious’ coding variants, some of which carry homozygous genotypes in the sequenced genome; the associated phenotypes include pharmacogenomic traits such as greater triglyceride lowering ability with fenofibrate treatment, and requirement of high warfarin dosage to elicit anticoagulation response. 6,328 non-coding SNPs associate with 811 phenotype traits: in congruence with medical history of the participant for Type 2 diabetes and β-Thalassemia, and of participant’s family for migraine, 72 (of 159 known) Type 2 diabetes, 3 (of 4) β-Thalassemia, and 76 (of 169) migraine variants are seen in the genome. Intergenome comparisons based on shared disease-causing variants, positions the sequenced genome between Asian and European genomes in congruence with geographical location of the region. On comparison, bead arrays perform better than sequencing platforms in correctly calling genotypes in low-coverage sequenced genome regions however in the event of novel SNP or indel near genotype calling position can lead to false calls using bead arrays. We report, for the first time, reference genome resource for the population of Persian ancestry. The resource provides a starting point for designing large-scale genetic studies in Peninsula including Kuwait, and Persian population. Such efforts on populations under-represented in global genome variation surveys help augment current knowledge on human genome diversity.
32 citations
Cites background from "Hemoglobin electrophoresis and hemo..."
...Thalassemia and Sickle cell anemia are the most prevalent genetic blood diseases in Kuwait [62,63]....
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TL;DR: There is need for development of a discrimination index to differentiate between α and β thalassemias traits on the lines of discriminatory Indices available for distinguishing βThalassemia trait from iron deficiency anemia.
Abstract: Background and Aims : Saudi Arabia falls in the high prevalent zone of αα and β thalassemias. Early screening for the type of thalassemia is essential for further investigations and management. The study was carried out to differentiate the type of thalassemia based on red cell indices and other hematological parameters. Materials and Methods : The study was carried out on 991 clinically suspected cases of thalassemias in Riyadh, Saudi Arabia. The hematological parameters were studied on Coulter STKS. Cellulose acetate hemoglobin electrophoresis and high-performance liquid chromatography (HPLC) were performed on all the blood samples. Gene deletion studies were carried out by restriction fragment length polymorphism (RFLP) technique using the restriction endonucleases Bam HI. Statistical Analysis : Statistical analysis was performed on SPSS 11.5 version. Results : The hemoglobin electrophoresis and gene studies revealed that there were 406 (40.96%) and 59 (5.95 %) cases of β thalassemia trait and β thalassemia major respectively including adults and children. 426 cases of various deletion forms of α thalassemias were seen. Microcytosis was a common feature in β thalassemias trait and (-α/-α) and (--/αα) types of α thalassemias. MCH was a more significant distinguishing feature among thalassemias. β thalassemia major and α thalassemia (-α/αα) had almost normal hematological parameters. Conclusion : MCV and RBC counts are not statistically significant features for discriminating between α and β thalassemias. There is need for development of a discrimination index to differentiate between α and β thalassemias traits on the lines of discriminatory Indices available for distinguishing β thalassemias trait from iron deficiency anemia.
16 citations
Cites background from "Hemoglobin electrophoresis and hemo..."
...The β thalassemia is prevalent throughout the world while α is found more in the Mediterranean region,[1] Middle East,[2-4] South Asia[5,6] and South East Asia....
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...[18] South East Asia,[7-9] India,[5,6] Mediterranean region[2-4] and Middle East including Saudi Arabia[2,14-17] are the regions from where large number of cases are reported....
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DOI•
31 Aug 2011
TL;DR: To identify abnormal Hb stratified tribe by tribe within a cohort of Sudanese patients attending the Khartoum Teaching Hospital between March and July 2005, cellulose acetate electrophoresis (CAE) and full blood count (FBC) were used to determine the Hb type.
Abstract: Haemoglobin (Hb) abnormalities are inherited disorders in the globin chains when the haem group is in the normal state. They are mostly autosomal recessive abnormalities and common worldwide, particularly within the malarial regions of Africa. This study aimed to identify abnormal Hb stratified tribe by tribe within a cohort of Sudanese patients attending the Khartoum Teaching Hospital between March and July 2005. Initially, cellulose acetate electrophoresis (CAE) and full blood count (FBC) were used to determine the Hb type. Cation-exchange-high performance liquid chromatography (CE-HPLC) was subsequently used to evaluate results. The following range was found: HbAA (93.1%), HbAS (5.1%), HbSS (1.0%), HbAC (0.6%) and HbCC (0.2%). Thus the S gene was the most common variant found (6.1%), and it was most prevalent in the western tribes of Sudan (12.5%). Other notable findings included three patients out of HbAA subjects (0.5%) with an increased Hb F. Results from CAE were validated with CE-HPLC and findings were identical. Additional quantitative data is available with CEHPLC, but it is expensive in terms of operation and maintenance. CAE therefore remains the technique of choice in developing countries. CAE is recommended as a suitable technique for clinical use in the developing world. Rates of genetic disorder can be reduced with improved health management and further research is also recommended into the presence of Hb F, hereditary persistence of foetal Hb (HPFH) and δβ-thalassaemia in HbAA.
12 citations
References
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TL;DR: It is argued that malaria selection has operated relatively recently on human populations (within the last 5000 years) and the present distribution of haemoglobinopathies is seen as the result of selection elevating sporadic mutations in local populations.
Abstract: The haemoglobinopathies are the commonest single-gene disorders known, almost certainly because of the protection they provide against malaria, as attested by a number of observations. The geographical distributions of malaria and haemoglobinopathies largely overlap, and microepidemiological surveys confirm the close relationship between them. For two of the commonest disorders, haemoglobin S and alpha(+)-thalassaemia, there is also good clinical evidence for protection against malaria morbidity. However, not all the evidence appears to support this view. In some parts of the world malaria and haemoglobinopathies are not, and never have been, coexistent. It is also difficult to explain why the majority of haemoglobinopathies appear to be recent mutations and are regionally specific. Here we argue that these apparent inconsistencies in the malaria hypothesis are the result of processes such as genetic drift and migration and of demographic changes that have occurred during the past 10,000 years. When these factors are taken into account, selection by malaria remains the force responsible for the prevalence of the haemoglobinopathies.
483 citations
TL;DR: Using amplification, allele-specific oligonucleotide (ASO) hybridization and DNA sequencing, the molecular basis of 64 α- and 123 β-thalassemia (thai) chromosomes, and the haplotypes is documented.
Abstract: Using amplification, allele-specific oligonucleotide (ASO) hybridization and DNA sequencing we have documented the molecular basis of 64 α- and 123 β-thalassemia (thai) chromosomes, and the haplotypes
100 citations
01 Jan 1986
TL;DR: The frequencies of four major red cell genetic defects, sickle haemoglobin (Hb S), glucose 6 phosphate dehydrogenase deficiency (G6PD), and alpha and beta thalassaemia, have been determined in nearly 5000 subjects from the three major Peninsular Arab States.
Abstract: The frequencies of four major red cell genetic defects, sickle haemoglobin (Hb S), glucose 6 phosphate dehydrogenase deficiency (G6PD), and alpha and beta thalassaemia, have been determined in nearly 5000 subjects from the three major Peninsular Arab States, namely Yemen (North and South), the United Arab Emirates, and Oman. All four defects are common with an overall pattern of alpha thalassaemia greater than G6PD deficiency greater than beta thalassaemia greater than Hb A/S. However, the frequencies of these within each state varies and they are, respectively, Oman: 0.389, 0.328, 0.024, and 0.038; the United Arab Emirates: 0.165, 0.087, 0.017, and 0.019; and Yemen: 0.065, 0.062, 0.0624, and 0.0095. Two, namely alpha thalassaemia and G6PD deficiency, are extremely common, but in spite of this there appears to be a lack of observed clinical disease. For example, Hb H disease and Barts hydrops fetalis were not seen and the oxidative haemolytic syndromes are rare.
73 citations
TL;DR: In this paper, the frequencies of four major red cell genetic defects (Hb S, G6PD, alpha and beta thalassaemia, and Hb A/S) have been determined in nearly 5000 subjects from the three major Peninsular Arab States, namely, Yemen (North and South), the United Arab Emirates, and Oman.
Abstract: The frequencies of four major red cell genetic defects, sickle haemoglobin (Hb S), glucose 6 phosphate dehydrogenase deficiency (G6PD), and alpha and beta thalassaemia, have been determined in nearly 5000 subjects from the three major Peninsular Arab States, namely Yemen (North and South), the United Arab Emirates, and Oman. All four defects are common with an overall pattern of alpha thalassaemia greater than G6PD deficiency greater than beta thalassaemia greater than Hb A/S. However, the frequencies of these within each state varies and they are, respectively, Oman: 0.389, 0.328, 0.024, and 0.038; the United Arab Emirates: 0.165, 0.087, 0.017, and 0.019; and Yemen: 0.065, 0.062, 0.0624, and 0.0095. Two, namely alpha thalassaemia and G6PD deficiency, are extremely common, but in spite of this there appears to be a lack of observed clinical disease. For example, Hb H disease and Barts hydrops fetalis were not seen and the oxidative haemolytic syndromes are rare.
71 citations