A Single Nucleotide Polymorphism in the<i>HBBP1</i>Gene in the Human β-Globin Locus is Associated with a Mild β-Thalassemia Disease Phenotype

Giannopoulou, Efstathia; Bartsakoulia, Marina; Tafrali, Christina; Kourakli, Alexandra; Poulas, Konstantinos; Stavrou, Eleana F.; Papachatzopoulou, Adamantia; Georgitsi, Marianthi; Patrinos, George P.

doi:10.3109/03630269.2012.717515

Cited by 23 publications

(13 citation statements)

References 28 publications

(25 reference statements)

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“…As single locus has a very modest effect on Type 2 Diabetes susceptibility and all the reported loci seem to partly account for the heritability of Type 2 Diabetes, it is difficult to say whether one or few or all of these 72 SNPs influence the phenotype in the individual (Additional file 12 : Table S8). The three β-Thalassemia variants observed in the sequenced genome are: rs766432 [2:g.60719970C > A] (seen as homozygous in the studied genome; intronic, BCL11A gene [MIM: *606557]) [ 42 ], rs9376092 [6:g.135427144C > A] (intergenic, HBS1L [MIM:*612450]-MYB [MIM: *189990] genes) [ 43 ], and rs2071348 [11:g.5264146 T > G] (intronic; HBBP1 gene) [ 44 , 45 ]. It has been reported that these three loci are the best and common predictors of the disease severity in β-Thalassemia [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

Sequence and analysis of a whole genome from Kuwaiti population subgroup of Persian ancestry

et al. 2015

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BackgroundThe 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.ResultsWe 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1233-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Sequence and analysis of a whole genome from Kuwaiti population subgroup of Persian ancestry

et al. 2015

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“…A gene in the beta-globin gene cluster is HBBP1, where the rs2071348 mutation increases HbF levels as well as MCH, leading to milder thalassemia symptoms (Giannopoulou et al 2012;Tomkins 2013).…”

Section: Hbbp1 Mutationmentioning

confidence: 99%

The Influence of Polymorphisms in Disease Severity in β-Thalassemia

et al. 2015

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β-Thalassemia is a genetic disorder with a continuum of mild to severe clinical manifestations and requirement of transfusion at different stages of life. The cause(s) of this variety is not clear but genetic alterations could be a potential factor. In this review, the correlation between polymorphisms and different clinical manifestations, including the need for transfusion, was investigated. Relevant articles published in pubmed database from 1982 onwards were studied and compiled. The articles all contained the keywords β-thalassemia, genetic modifiers, and mutations. Certain polymorphisms and mutations could dictate the severity of symptoms as well as their onset. A significant number of the mentioned genetic alterations appear in beta-globin gene cluster and affect gamma chain. Therefore, hemoglobin F production rate is increased and can affect thalassemia symptoms and can relieve β-thalassemia symptoms. A number of polymorphisms in catalase and glutathione S transferase genes have also been shown to modify the severity of disease and response to treatment. Knowledge of these mutations and polymorphisms can provide an insight into the prognosis for individual patients, especially in young ages or before birth to take proper measures in advance and eventually ameliorate the symptoms in the long run.

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“…A typical example is the human β-globin pseudogene, which, while not coding for a protein, produces a variety of regulatory RNAs. Mutations in this pseudogene have been associated with blood diseases [45]. Another line of evidence for the functionality of some pseudogenes is that many are transcribed.…”

Section: Functional Pseudogenesmentioning

confidence: 99%

Pseudogenes and Their Genome-Wide Prediction in Plants

Xiao

Sekhwal

et al. 2016

IJMS

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Pseudogenes are paralogs generated from ancestral functional genes (parents) during genome evolution, which contain critical defects in their sequences, such as lacking a promoter, having a premature stop codon or frameshift mutations. Generally, pseudogenes are functionless, but recent evidence demonstrates that some of them have potential roles in regulation. The majority of pseudogenes are generated from functional progenitor genes either by gene duplication (duplicated pseudogenes) or retro-transposition (processed pseudogenes). Pseudogenes are primarily identified by comparison to their parent genes. Bioinformatics tools for pseudogene prediction have been developed, among which PseudoPipe, PSF and Shiu’s pipeline are publicly available. We compared these three tools using the well-annotated Arabidopsis thaliana genome and its known 924 pseudogenes as a test data set. PseudoPipe and Shiu’s pipeline identified ~80% of A. thaliana pseudogenes, of which 94% were shared, while PSF failed to generate adequate results. A need for improvement of the bioinformatics tools for pseudogene prediction accuracy in plant genomes was thus identified, with the ultimate goal of improving the quality of genome annotation in plants.

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A Single Nucleotide Polymorphism in theHBBP1Gene in the Human β-Globin Locus is Associated with a Mild β-Thalassemia Disease Phenotype

Cited by 23 publications

References 28 publications

Sequence and analysis of a whole genome from Kuwaiti population subgroup of Persian ancestry

Sequence and analysis of a whole genome from Kuwaiti population subgroup of Persian ancestry

The Influence of Polymorphisms in Disease Severity in β-Thalassemia

Pseudogenes and Their Genome-Wide Prediction in Plants

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