Genomes and Genes
Gene Symbol: HBB
Description: hemoglobin subunit beta
Alias: CD113t-C, beta-globin, hemoglobin subunit beta, beta globin chain, hemoglobin, beta
- Shaji R, Edison E, Poonkuzhali B, Srivastava A, Chandy M. Rapid detection of beta-globin gene mutations and polymorphisms by temporal temperature gradient gel electrophoresis. Clin Chem. 2003;49:777-81 pubmed..Compared with other approaches for comprehensive mutation screening, the reported method is rapid, highly sensitive, cost-effective, and suitable for high-throughput screening of a large number of samples. ..
- Papachatzopoulou A, Kaimakis P, Pourfarzad F, Menounos P, Evangelakou P, Kollia P, et al. Increased gamma-globin gene expression in beta-thalassemia intermedia patients correlates with a mutation in 3'HS1. Am J Hematol. 2007;82:1005-9 pubmed..We conclude that the CH haplotypes are useful genetic determinants for beta-thalassemia major and intermedia patients, while the 3'HS1 (+179 C>T) mutation may have functional consequences in gamma-globin genes expression. ..
- Li Q, Zhang M, Han H, Rohde A, Stamatoyannopoulos G. Evidence that DNase I hypersensitive site 5 of the human beta-globin locus control region functions as a chromosomal insulator in transgenic mice. Nucleic Acids Res. 2002;30:2484-91 pubmed..The 5'HS5 insulator operates in adult as well as in embryonic murine erythroid cells. The insulator has no significant stimulatory effects of its own. These results indicate that 5'HS5 can function as a chromatin insulator in vivo. ..
- Aidoo M, Terlouw D, Kolczak M, McElroy P, Ter Kuile F, Kariuki S, et al. Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet. 2002;359:1311-2 pubmed..These data are important in understanding the role of malaria in the selection and maintenance of the sickle cell gene. ..
- Wood E, Stover D, Slatkin M, Nachman M, Hammer M. The beta -globin recombinational hotspot reduces the effects of strong selection around HbC, a recently arisen mutation providing resistance to malaria. Am J Hum Genet. 2005;77:637-42 pubmed..The rapid decay in LD upstream of the HbC allele demonstrates the large effect the ss-globin hotspot has in mitigating the effects of positive selection on linked variation. ..
- Fairhurst R, Baruch D, Brittain N, Ostera G, Wallach J, Hoang H, et al. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature. 2005;435:1117-21 pubmed..Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature. ..
- Fang X, Xiang P, Yin W, Stamatoyannopoulos G, Li Q. Cooperativeness of the higher chromatin structure of the beta-globin locus revealed by the deletion mutations of DNase I hypersensitive site 3 of the LCR. J Mol Biol. 2007;365:31-7 pubmed..Taken together, these results suggest that the formation of the ACH is dependent on a largely intact LCR structure. We propose that the ACH indeed is an extension of the LCR holocomplex. ..
- Kim A, Kiefer C, Dean A. Distinctive signatures of histone methylation in transcribed coding and noncoding human beta-globin sequences. Mol Cell Biol. 2007;27:1271-9 pubmed..Most epigenetic and chromatin structural features did not undergo transitions at the presumed borders of the globin domain where the insulator factor CTCF interacts, raising questions about the function of the borders. ..
- Tanimoto K, Sugiura A, Omori A, Felsenfeld G, Engel J, Fukamizu A. Human beta-globin locus control region HS5 contains CTCF- and developmental stage-dependent enhancer-blocking activity in erythroid cells. Mol Cell Biol. 2003;23:8946-52 pubmed..These observations demonstrate that the phenotype observed in the LCR-inverted locus was in part attributable to placing the HS5 insulator between the LCR HS enhancers (HS1 to HS4) and the promoter of the beta-globin gene. ..
- Uda M, Galanello R, Sanna S, Lettre G, Sankaran V, Chen W, et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad Sci U S A. 2008;105:1620-5 pubmed publisher..We expect our findings will help to characterize the molecular mechanisms of fetal globin regulation and could eventually contribute to the development of new therapeutic approaches for beta-thalassemia and sickle cell anemia. ..
- Farrell C, West A, Felsenfeld G. Conserved CTCF insulator elements flank the mouse and human beta-globin loci. Mol Cell Biol. 2002;22:3820-31 pubmed
- Ma Q, Abel K, Sripichai O, Whitacre J, Angkachatchai V, Makarasara W, et al. Beta-globin gene cluster polymorphisms are strongly associated with severity of HbE/beta(0)-thalassemia. Clin Genet. 2007;72:497-505 pubmed..Further studies are needed to validate this hypothesis and determine whether XmnI or another closely linked variant modulates severity and HbF levels in patients with beta(0)-thalassemia/HbE disease. ..
- Kim A, Dean A. A human globin enhancer causes both discrete and widespread alterations in chromatin structure. Mol Cell Biol. 2003;23:8099-109 pubmed
- Kaushik M, Kukreti R, Grover D, Brahmachari S, Kukreti S. Hairpin-duplex equilibrium reflected in the A-->B transition in an undecamer quasi-palindrome present in the locus control region of the human beta-globin gene cluster. Nucleic Acids Res. 2003;31:6904-15 pubmed..We propose that quasi-palindromic sequences may form stable mini- hairpins or cruciforms in the HS4 region and might play a role in regulating beta-globin gene expression by affecting the binding of transcription factors. ..
- Zhu J, Kren B, Park C, Bilgim R, Wong P, Steer C. Erythroid-specific expression of beta-globin by the sleeping beauty transposon for Sickle cell disease. Biochemistry. 2007;46:6844-58 pubmed..The SB-Tn system is a promising nonviral vector for efficient genomic insertion conferring stable, persistent erythroid-specific expression of beta-globin. ..
- Webster M, Clegg J, Harding R. Common 5' beta-globin RFLP haplotypes harbour a surprising level of ancestral sequence mosaicism. Hum Genet. 2003;113:123-39 pubmed
- Jiang Y, Xu X, Russell J. A nucleolin-binding 3' untranslated region element stabilizes beta-globin mRNA in vivo. Mol Cell Biol. 2006;26:2419-29 pubmedThe normal expression of human beta globin is critically dependent upon the constitutively high stability of its encoding mRNA...
- Brown J, Leach J, Reittie J, Atzberger A, Lee Prudhoe J, Wood W, et al. Coregulated human globin genes are frequently in spatial proximity when active. J Cell Biol. 2006;172:177-87 pubmed
- Routledge S, Proudfoot N. Definition of transcriptional promoters in the human beta globin locus control region. J Mol Biol. 2002;323:601-11 pubmedOur previous studies on the human beta globin gene cluster revealed the presence of intergenic transcripts throughout the locus, and demonstrated that transcription of the locus control region (LCR) initiates within an ERV9 endogenous ..
- Hanchard N, Hambleton I, Harding R, McKenzie C. The frequency of the sickle allele in Jamaica has not declined over the last 22 years. Br J Haematol. 2005;130:939-42 pubmed..Refining the expectations for allele and trait frequency change for Jamaica and other similar populations is an area for future study. ..
- Moormann A, Embury P, Opondo J, Sumba O, Ouma J, Kazura J, et al. Frequencies of sickle cell trait and glucose-6-phosphate dehydrogenase deficiency differ in highland and nearby lowland malaria-endemic areas of Kenya. Trans R Soc Trop Med Hyg. 2003;97:513-4 pubmed..Lack of protective polymorphisms may contribute to morbidity and mortality during outbreaks of malaria in the highlands. ..
- Patrinos G, de Krom M, de Boer E, Langeveld A, Imam A, Strouboulis J, et al. Multiple interactions between regulatory regions are required to stabilize an active chromatin hub. Genes Dev. 2004;18:1495-509 pubmed..We conclude that multiple interactions between the LCR and the beta-globin gene are required to maintain the appropriate spatial configuration in vivo. ..
- Bhardwaj U, Zhang Y, Lorey F, McCabe L, McCabe E. Molecular genetic confirmatory testing from newborn screening samples for the common African-American, Asian Indian, Southeast Asian, and Chinese beta-thalassemia mutations. Am J Hematol. 2005;78:249-55 pubmed..Multiplexed ARMS for ethnic-specific beta-thalassemia mutations from the original newborn screening dried blood specimens is a rapid and efficient approach for diagnostic confirmation. ..
- Atkinson S, Rockett K, Sirugo G, Bejon P, Fulford A, O Connell M, et al. Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2 genotype. PLoS Med. 2006;3:e172 pubmed..The magnitude of the effect of haptoglobin genotype (4 g/l Hb difference, p = 0.0009) was comparable to that of G6PD deficiency or HbAS (3 g/l difference, p = 0.03; and 2 g/l difference, p = 0.68, respectively). ..
- Layon M, Ackley C, West R, Lowrey C. Expression of GATA-1 in a non-hematopoietic cell line induces beta-globin locus control region chromatin structure remodeling and an erythroid pattern of gene expression. J Mol Biol. 2007;366:737-44 pubmed..These results imply that GATA-1 is sufficient to direct chromatin structure reorganization within the beta-globin LCR and an erythroid pattern of gene expression in the absence of other hematopoietic transcription factors. ..
- Ostermeier G, Liu Z, Martins R, Bharadwaj R, Ellis J, Draghici S, et al. Nuclear matrix association of the human beta-globin locus utilizing a novel approach to quantitative real-time PCR. Nucleic Acids Res. 2003;31:3257-66 pubmed..These results provide the first evidence that nuclear matrix association dynamically mediates the looping of the beta-globin locus to achieve transcriptional control...
- Richter F, Meurers B, Zhu C, Medvedeva V, Chesselet M. Neurons express hemoglobin alpha- and beta-chains in rat and human brains. J Comp Neurol. 2009;515:538-47 pubmed publisher..and striatal neurons in mice revealed the presence of hemoglobin alpha, adult chain 2 (Hba-a2) and hemoglobin beta (Hbb) transcripts, whereas other erythroid markers were not detected...
- Nuntakarn L, Fucharoen S, Fucharoen G, Sanchaisuriya K, Jetsrisuparb A, Wiangnon S. Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-beta-thalassemia in Northeast Thailand. Blood Cells Mol Dis. 2009;42:32-5 pubmed publisher..Our data reveals that in the majority of these Hb E-beta-thalassemia patients, it is very hard to predict the clinical phenotype of the patients from the beta-globin mutations and these secondary genetic modifiers. ..
- Wang L, Lin C, Brooks S, Cimbora D, Groudine M, Aladjem M. The human beta-globin replication initiation region consists of two modular independent replicators. Mol Cell Biol. 2004;24:3373-86 pubmed
- Orkin S, Kazazian H, Antonarakis S, Goff S, Boehm C, Sexton J, et al. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature. 1982;296:627-31 pubmed
- Currat M, Trabuchet G, Rees D, Perrin P, Harding R, Clegg J, et al. Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta(S) Senegal mutation. Am J Hum Genet. 2002;70:207-23 pubmed
- Yoshioka N, Atassi M. Haemoglobin binding with haptoglobin. Localization of the haptoglobin-binding sites on the beta-chain of human haemoglobin by synthetic overlapping peptides encompassing the entire chain. Biochem J. 1986;234:453-6 pubmed
- Orkin S, Goff S. Nonsense and frameshift mutations in beta 0-thalassemia detected in cloned beta-globin genes. J Biol Chem. 1981;256:9782-4 pubmed..This frameshift mutation produced a termination codon at the position of the new 21st codon. Mutations that lead to premature termination of beta-globin synthesis appear to be among the common causes of beta 0-thalassemia in man. ..
- Lykke Andersen J, Shu M, Steitz J. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell. 2000;103:1121-31 pubmed..These data suggest that assembly of a dynamic hUpf complex initiates in the nucleus at mRNA exon-exon junctions and triggers NMD in the cytoplasm when recognized downstream of a translation termination site. ..
- Fullerton S, Harding R, Boyce A, Clegg J. Molecular and population genetic analysis of allelic sequence diversity at the human beta-globin locus. Proc Natl Acad Sci U S A. 1994;91:1805-9 pubmed..Nucleotide diversity at synonymous sites in the sample is 0.14%, suggesting an average age of sequence divergence of approximately 450,000 years, consistent with that expected for a neutrally evolving human nuclear locus. ..
- Giardina B, Messana I, Scatena R, Castagnola M. The multiple functions of hemoglobin. Crit Rev Biochem Mol Biol. 1995;30:165-96 pubmed
- Demers C, Chaturvedi C, Ranish J, Juban G, Lai P, Morle F, et al. Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locus. Mol Cell. 2007;27:573-84 pubmed
- Ortiz A, Romaguera J, PÃ©rez C, GonzÃ¡lez D, MuÃ±oz C, GonzÃ¡lez L, et al. Prevalence, genotyping, and correlates of anogenital HPV infection in a population-based sample of women in Puerto Rico. Papillomavirus Res. 2016;2:89-96 pubmed publisher..As vaccination increases, future studies should monitor changing trends in HPV infection in this population, and the relationship between anal and cervical HPV-related disease. ..
- Vermeulen C, Geeven G, de Wit E, Verstegen M, Jansen R, van Kranenburg M, et al. Sensitive Monogenic Noninvasive Prenatal Diagnosis by Targeted Haplotyping. Am J Hum Genet. 2017;101:326-339 pubmed publisher..MG-NIPD was validated for 18 pregnancies, focusing on CFTR, CYP21A2, and HBB. In all cases we could predict the inherited alleles with >98% confidence, even at relatively early stages (8Â ..
- Newman M, Nguyen T, Watson M, Hull R, Yu H. Transcriptome profiling reveals novel BMI- and sex-specific gene expression signatures for human cardiac hypertrophy. Physiol Genomics. 2017;49:355-367 pubmed publisher..2 or extremely small P value (10-20) as a criterion, we identified nine significant genes (HBA1, HBB, HIST1H2AC, GSTT1, MYL7, NPPA, NPPB, PDK4, PLA2G2A) in LVH, also found in published data set for ischemic and ..
- Bastani M, Bokharaei Salim F, Keyvani H, Esghaei M, Monavari S, Ebrahimi M, et al. Prevalence of occult hepatitis C virus infection in Iranian patients with beta thalassemia major. Arch Virol. 2016;161:1899-906 pubmed publisher..These results revealed that Iranian patients with beta-thalassemia major might have OCI. Therefore, it seems that the design of a study to identify this infection in patients with ?-thalassemia major would provide valuable information. ..
- De La Mora J, Uchida K, del Campo A, Camarena L, Aizawa S, Dreyfus G. Structural Characterization of the Fla2 Flagellum of Rhodobacter sphaeroides. J Bacteriol. 2015;197:2859-66 pubmed publisher..6 on average. By comparison with the Fla1 flagellum, the prominent features of the ultra structure of the Fla2 HBB are the absence of an H ring, thick and long hooks, and a smoother zone at the hook-filament junction...
- Inati A, Abbas H, Al Danaf J, Souaid M, Kahale M, Koussa S, et al. Identification of the first mutation in a BRE motif of the ?-globin gene and its inheritance with two other ?-globin gene mutations in a Lebanese family. Hemoglobin. 2013;37:171-5 pubmed publisher..The proband and his sibling also inherited common ?-globin mutations from the father and mother. In all cases, no serious thalassemia disease was detected. ..
- Silva M, Sendin S, Velloso Rodrigues C, Belisário A, D Ávila T, Lyra L, et al. Unstable hemoglobin Rush [beta 101(G3) Glu>Gln, HBB:c.304G>C] in a Brazilian family with moderate hemolytic anemia. Ann Hematol. 2012;91:1091-6 pubmed publisher..8%. The intensity of hemolysis appeared to be linked to increased stress. The mutation was proved to be HBB:c.304G>C, beta 101(G3) Glu>Gln...
- Belisário A, Martins M, Brito A, Rodrigues C, Silva C, Viana M. ?-globin gene cluster haplotypes in a cohort of 221 children with sickle cell anemia or S??-thalassemia and their association with clinical and hematological features. Acta Haematol. 2010;124:162-70 pubmed publisher..Furthermore, ?(S)-haplotypes CAR and Ben were not associated with any analyzed feature of children with sickle cell anemia. ..
- Onakoya P, Nwaorgu O, Shokunbi W. Hearing impairment in persons with the hemoglobin SC genotype. Ear Nose Throat J. 2010;89:306-10 pubmed..2%) and 10 of 15 (66.7%) (chi(2) = 26.840; p < 0.001). Therefore, we conclude that the hearing loss in the subjects of this study was a function of age and was not associated with the presence of the Hb SC genotype. ..
- Georgiou I, Makis A, Chaidos A, Bouba I, Hatzi E, Kranas V, et al. Distribution and frequency of beta-thalassemia mutations in northwestern and central Greece. Eur J Haematol. 2003;70:75-8 pubmed..Furthermore, the detailed distribution tables of beta-thalassemia mutations are essential for counseling and extraction of genetic diversity estimates for population genetic studies in other inherited disorders. ..
- Svasti S, Boonchoy C, Vanichsetakul P, Winichagoon P, Fucharoen S. Molecular mechanism of beta-thalassaemia caused by 22-bp duplication. Ann Hematol. 2008;87:633-7 pubmed publisher..beta-Globin messenger ribonucleic acid (mRNA) transcribed from the mutant gene was not detected, suggesting that the process of nonsense-mediated mRNA decay may be triggered by the premature stop codon. ..
- Azimi A, Alibakhshi R, Hayati H, Tahmasebi S, Alimoradi S. IVS-II-648/649 (-T) (HBB: c.316-202del) Triggers a Novel ?-Thalassemia Phenotype. Hemoglobin. 2017;41:44-46 pubmed publisher..In this study, we identified a novel mutation in a 21-year-old woman [IVS-II-648/649 (-T); HBB: c.316-202del)] and describe its clinical implications...
- Hamid M, Akbari M. A 13-bp deletion in the 3' untranslated region of the ?-globin gene causes ?-thalassemia major in compound heterozygosity with IVSII-1 mutation. Med Princ Pract. 2011;20:488-90 pubmed publisher..The 13-bp deletion could be clinically important only in situations where ?-chain synthesis in trans is compromised. ..
- Miri Moghaddam E, Zadeh Vakili A, Nikravesh A, Sistani S, Naroie Nejad M. Sistani population: a different spectrum of ?-thalassemia mutations from other ethnic groups of Iran. Hemoglobin. 2013;37:138-47 pubmed publisher..These results could greatly facilitate timely and accurate PND. ..
- Taghavi Basmanj M, Karimipoor M, Amirian A, Jafarinejad M, Katouzian L, Valaei A, et al. Co-inheritance of hemoglobin D and ?-thalassemia traits in three Iranian families: clinical relevance. Arch Iran Med. 2011;14:61-3 pubmed publisher..Hematological studies of the family members showed that thalassemia which caused the mutations and Hb D were in the trans position. ..
- Lohani N, Bhargava N, Munshi A, Ramalingam S. Pharmacological and molecular approaches for the treatment of ?-hemoglobin disorders. J Cell Physiol. 2017;: pubmed publisher..These disorders are caused by mutations in the gene encoding hemoglobin-? (HBB), a vital protein found in red blood cells (RBCs) that carries oxygen from lungs to all parts of the human body...
- Calvo S, Pagliarini D, Mootha V. Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proc Natl Acad Sci U S A. 2009;106:7507-12 pubmed publisher..Together, our results suggest that uORFs influence the protein expression of thousands of mammalian genes and that variation in these elements can influence human phenotype and disease. ..
- Elderdery A, Mills J, Mohamed B, Cooper A, Mohammed A, Eltieb N, et al. Molecular analysis of the ?-globin gene cluster haplotypes in a Sudanese population with sickle cell anaemia. Int J Lab Hematol. 2012;34:262-6 pubmed publisher..8%, possibly represented a new Sudan haplotype. ?(S) Haplotyes were demonstrated successfully from dried blood samples. A new haplotype is apparent in Sudan, in addition to the four African haplotypes. ..
- Hsu P, Wu D, Blutreich A, Kurtin P, Hoyer J, Karayalcin G. Spontaneous mutation of hemoglobin Lufkin in a white boy. J Pediatr Hematol Oncol. 2009;31:281-4 pubmed publisher..DNA sequencing of the beta globin gene confirmed a GGC to a GAC mutation at codon 29 (gly to asp) for Hb Lufkin on the patient and also revealed ..
- Lou J, Li Q, Wei X, Huang J, Xu X. Identification of the linkage of a 1.357 KB beta-globin gene deletion and A gamma-globin gene triplication in a Chinese family. Hemoglobin. 2010;34:343-53 pubmed publisher..Haplotype analyses indicated that the unusual form of the beta-globin gene deletion and gamma-globin gene triplication in cis were linked to halotype [+ - - - - - -]. ..
- Rujan I, Russu I. Allosteric effects of chloride ions at the intradimeric alpha1beta1 and alpha2beta2 interfaces of human hemoglobin. Proteins. 2002;49:413-9 pubmed..Therefore, the ligand-induced changes at the Hisalpha103(G10) sites are modulated by the allosteric effect of chloride ions on hemoglobin. ..
- Da Luz J, Kimura E, Costa F, Sonati M, Sans M. Beta-globin gene cluster haplotypes in Afro-Uruguayans from two geographical regions (South and North). Am J Hum Biol. 2010;22:124-8 pubmed publisher..The differences observed between both Uruguayan regions could be explained by microevolutionary events as genetic drift, founder effects, differential admixture, and/or distinct origin of the African slaves introduced in those regions. ..
- Samara M, Chiotoglou I, Kalamaras A, Likousi S, Chassanidis C, Vagena A, et al. Large-scale population genetic analysis for hemoglobinopathies reveals different mutation spectra in central Greece compared to the rest of the country. Am J Hematol. 2007;82:634-6 pubmed..Our data indicate that determination of mutation frequencies in different regions is vital for accurate provision of genetic services and counseling and for precise estimation of genetic diversity...
- Kiani A, Mortazavi Y, Zeinali S, Shirkhani Y. The molecular analysis of beta-thalassemia mutations in Lorestan Province, Iran. Hemoglobin. 2007;31:343-9 pubmed..7% of the mutations. These data showed that the spectrum of mutations found in Lorestan Province was different from those reported from other thalassemic regions of Iran and also of some neighboring countries. ..
- Chakrabarti P, Gupta R, Mishra A, Rai M, Singh V, Dash D. Spectrum of beta-thalassemia mutations in North Indian states: a beta-thalassemia trait with two mutations in cis. Clin Biochem. 2005;38:576-8 pubmed..F.S 8/9 (+G), as well as IVS1 nt5 (G --> C), are the major mutations in Indian states; however, the possibility of multiple mutations in cis in a fetus with the thalassemia trait has to be considered in a prenatal screening program. ..