Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population
Fetal hemoglobin (HbF) is a determining factor for the development of sickle cell anemia. High HbF levels lower the intensity of symptoms of this disease. HbF levels can vary in patients with sickle cell anemia and individuals without the disease. The purpose of this study was to identify the geneti...
- Autores:
-
Fong, Cristian
Mendoza, Yesica
Barreto, Guillermo
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2020
- Institución:
- Universidad Cooperativa de Colombia
- Repositorio:
- Repositorio UCC
- Idioma:
- OAI Identifier:
- oai:repository.ucc.edu.co:20.500.12494/32912
- Acceso en línea:
- http://dx.doi.org/10.1590/1678-4685-GMB-2019-0076
https://hdl.handle.net/20.500.12494/32912
- Palabra clave:
- Sickle cell anemia
Fetal hemoglobin
Gamma globin
Regulation of gene expression
Colombia
- Rights
- openAccess
- License
- Atribución
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| dc.title.spa.fl_str_mv |
Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population |
| title |
Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population |
| spellingShingle |
Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population Sickle cell anemia Fetal hemoglobin Gamma globin Regulation of gene expression Colombia |
| title_short |
Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population |
| title_full |
Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population |
| title_fullStr |
Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population |
| title_full_unstemmed |
Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population |
| title_sort |
Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population |
| dc.creator.fl_str_mv |
Fong, Cristian Mendoza, Yesica Barreto, Guillermo |
| dc.contributor.author.none.fl_str_mv |
Fong, Cristian Mendoza, Yesica Barreto, Guillermo |
| dc.subject.spa.fl_str_mv |
Sickle cell anemia Fetal hemoglobin Gamma globin Regulation of gene expression Colombia |
| topic |
Sickle cell anemia Fetal hemoglobin Gamma globin Regulation of gene expression Colombia |
| description |
Fetal hemoglobin (HbF) is a determining factor for the development of sickle cell anemia. High HbF levels lower the intensity of symptoms of this disease. HbF levels can vary in patients with sickle cell anemia and individuals without the disease. The purpose of this study was to identify the genetic variants in the G gamma-globin gene promoter that can modulate HbF expression in patients with sickle cell anemia and healthy individuals from Colombia. In total, 413 bp of the G gamma-globin gene promoter were sequenced in 60 patients with sickle cell anemia and 113 healthy individuals. The allelic and genotype frequencies of the identified variants were compared between individuals with low and high HbF for both patients and healthy individuals. In total, we identified 15 variants in both groups, only three of which were shared between patients and healthy individuals. In healthy individuals, sites -16 and -309 (rs112479156) exhibited differences in allele frequencies. The mutant allele of -16 lowered the production of HbF, whereas the mutant allele of -309 increased its production. These results reveal the presence of different mechanisms of HbF regulation between patients with sickle cell and healthy individuals. |
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2020 |
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2020-03 |
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2021-01-27T23:58:43Z |
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2021-01-27T23:58:43Z |
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Artículos Científicos |
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1678-4685 |
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http://dx.doi.org/10.1590/1678-4685-GMB-2019-0076 |
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https://hdl.handle.net/20.500.12494/32912 |
| dc.identifier.bibliographicCitation.spa.fl_str_mv |
Fong, C., Mendoza, Y. y Barreto, G.(2020) Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population. Genet Mol Biol. 2020;43(2):e20190076. |
| identifier_str_mv |
1678-4685 Fong, C., Mendoza, Y. y Barreto, G.(2020) Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population. Genet Mol Biol. 2020;43(2):e20190076. |
| url |
http://dx.doi.org/10.1590/1678-4685-GMB-2019-0076 https://hdl.handle.net/20.500.12494/32912 |
| dc.relation.ispartofjournal.spa.fl_str_mv |
Journal Genetics & molecular biology |
| dc.relation.references.spa.fl_str_mv |
Akinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT, Sebastiani P, Chui DHK and Steinberg MH (2011) Fetal hemoglobin in sickle cell anemia. Blood 118:19–27 Amrolia PJ, Cunningham JM, Ney P, Nienhuis AW and Jane SM (1995) Identification of two novel regulatory elements within the 5’-untranslated region of the human A gammaglobin gene. J Biol Chem 270:12892–12898 Attila G, Yalin S, Tuli A, Yalin E and Aksoy K (2004) Prenatal diagnosis of sickle cell anemia in twin pregnancies and identification by VNTRs. Clin Chim Acta 350:137–142. Bank A (2006) Regulation of human fetal hemoglobin: new players, new complexities. Blood 107:435–443. Barbosa CG, Goncalves-Santos NJ, Souza-Ribeiro SB, MouraNeto JP, Takahashi D, Silva DO, Hurtado-Guerrero AF, Reis MG and Goncalves MS (2010) Promoter region sequence differences in the A and G gamma globin genes of Brazilian sickle cell anemia patients. Braz J Med Biol Res 43:705–711. Barrett JC, Fry B, Maller J and Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265. Basak A and Sankaran VG (2016) Regulation of the fetal hemoglobin silencing factor BCL11A. Ann N Y Acad Sci 1368:25–30. de Vooght KMK, van Wijk R, Ploos van Amstel HK and van Solinge WW (2007) Characterization of the -16C>G sequence variation in the promoters of both HBG1 and HBG2: Convergent evolution of the human -globin genes. Blood Cells Mol Dis 39:70–74 Dulmovits BM, Appiah-Kubi AO, Papoin J, Hale J, He M, AlAbed Y, Didier S, Gould M, Husain-Krautter S, Singh SA et al. (2016) Pomalidomide reverses -globin silencing through the transcriptional reprograming of adult hematopoietic progenitors. Blood 127:1481–1492 Excoffier L and Lischer HEL (2010) Arlequin suite ver 3.5: a new series of programs to perform population genetics analyzes under Linux and Windows. Mol Ecol Resour 10:564–567. Fong C, Lizarralde-Iragorri MA, Rojas-Gallardo D and Barreto G (2013) Frequency and origin of haplotypes associated with the beta-globin gene cluster in individuals with trait and sickle cell anemia in the Atlantic and Pacific coastal regions of Colombia. Genet Mol Biol 36:494–497. Garner C, Tatu T, Reittie JE, Littlewood T, Darley J, Cervino S, Farrall M, Kelly P, Spector TD and Thein SL (2000) Genetic influences on F cells and other hematologic variables: a twin heritability study. Blood 95:342–346. Gilman JG and Huisman TH (1984) Two independent genetic factors in the beta-globin gene cluster are associated with high G gamma-levels in the HbF of SS patients. Blood 64:452–457. Hebbel RP, Osarogiagbon R and Kaul D (2004) The endothelial biology of sickle cell disease: Inflammation and a chronic vasculopathy. Microcirculation 11:129–151. Hilbe JM (2007) STATISTICA 7: an overview. Am Stat 61:91–94. Jane SM, Ney PA, Vanin EF, Gumucio DL and Nienhuis AW (1992) Identification of a stage selector element in the human gamma-globin gene promoter that fosters preferential interaction with the 5’ HS2 enhancer when in competition with the beta-promoter. EMBO J 11:2961–2969. Li Q, Fang X, Olave I, Han H, Yu M, Xiang P and Stamatoyannopoulos G (2006) Transcriptional potential of the -globin gene is dependent on the CACCC box in a developmental stage-specific manner. Nucleic Acids Res 34:3909–3916. Liu L, Pertsemlidis A, Ding LH, Story MD, Steinberg MH, Sebastiani P, Hoppe C, Ballas SK and Pace BS (2016) A casecontrol genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease. Exp Biol Med 241:706–718. Liu N, Hargreaves VV, Hong J, Kim W, Kurland J, Zhu Q, Sher F, Macias-Trevino C, Rogers J, Yuan GC et al. (2017) Fetal Hemoglobin (HbF) Silencer BCL11A acts through a novel DNA motif in the gamma-globin promoters, symplifying the model for hemoglobin switching. Blood 130:283. Martyn GE, Quinlan KGR and Crossley M (2017) The regulation of human globin promoters by CCAAT box elements and the recruitment of NF-Y. Biochim Biophys Acta Gene Regul Mech 1860:525–536. Menzel S, Jiang J, Silver N, Gallagher J, Cunningham J, Surdulescu G, Lathrop M, Farrall M, Spector TD and Thein SL (2007) The HBS1L-MYB intergenic region on chromosome 6q23.3 influences erythrocyte, platelet, and monocyte counts in humans. Blood 110:3624–3626. Miller SA, Dykes DD and Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215. Ossa H, Aquino J, Pereira R, Ibarra A, Ossa RH, Pérez LA, Granda JD, Lattig MC, Groot H, Fagundes de Carvalho E et al. (2016) Outlining the ancestry landscape of Colombian admixed populations. PLoS One 11:e0164414 Pauling L, Itano HA, Singer SJ and Wells IC (1949) Sickle cell anemia a molecular disease. Science 110:543–548. Powars DR, Weiss JN, Chan LS and Schroeder WA (1984) Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia? Blood 63:921–926. Pule GD, Ngo Bitoungui VJ, Chetcha Chemegni B, Kengne AP and Wonkam A (2016) Studies of novel variants associated with Hb F in Sardinians and Tanzanians in sickle cell disease patients from Cameroon. Hemoglobin 40:377–380. Raymond M and Rousset F (1995) An exact test for population differentiation. Evolution 49:1280–1283. Rochette J, Craig JE and Thein SL (1994) Fetal hemoglobin levels in adults. Blood Rev 8:213–224. Singer K, Chernoff AI and Singer L (1951) Studies on Abnormal Hemoglobins: I. Their demonstration in sickle cell anemia and orther hematologic disorders by means of alkali denaturation. Blood 6:413–428. Solovieff N, Milton JN, Hartley SW, Sherva R, Sebastiani P, Dworkis DA, Klings ES, Farrer LA, Garrett ME, AshleyKoch A et al. (2010) Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5’ olfactory receptor gene cluster. Blood 115:1815–1822. Steinberg MH, Lu ZH, Barton FB, Terrin ML, Charache S and Dover GJ (1997) Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea. Blood 89:1078–1088. Thein SL and Menzel S (2009) Discovering the genetics underlying foetal haemoglobin production in adults. Br J Haematol 145:455–467. Traxler EA, Yao Y, Wang YD, Woodard KJ, Kurita R, Nakamura Y, Hughes JR, Hardison RC, Blobel GA, Li C et al. (2016) A genome-editing strategy to treat -hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat Med 22:987–990. Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, Usala G, Busonero F, Maschio A, Albai G et al. (2008) Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad SciUSA 105:1620–1625. A |
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Fong, CristianMendoza, YesicaBarreto, Guillermo432021-01-27T23:58:43Z2021-01-27T23:58:43Z2020-031678-4685http://dx.doi.org/10.1590/1678-4685-GMB-2019-0076https://hdl.handle.net/20.500.12494/32912Fong, C., Mendoza, Y. y Barreto, G.(2020) Genetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian population. Genet Mol Biol. 2020;43(2):e20190076.Fetal hemoglobin (HbF) is a determining factor for the development of sickle cell anemia. High HbF levels lower the intensity of symptoms of this disease. HbF levels can vary in patients with sickle cell anemia and individuals without the disease. The purpose of this study was to identify the genetic variants in the G gamma-globin gene promoter that can modulate HbF expression in patients with sickle cell anemia and healthy individuals from Colombia. In total, 413 bp of the G gamma-globin gene promoter were sequenced in 60 patients with sickle cell anemia and 113 healthy individuals. The allelic and genotype frequencies of the identified variants were compared between individuals with low and high HbF for both patients and healthy individuals. In total, we identified 15 variants in both groups, only three of which were shared between patients and healthy individuals. In healthy individuals, sites -16 and -309 (rs112479156) exhibited differences in allele frequencies. The mutant allele of -16 lowered the production of HbF, whereas the mutant allele of -309 increased its production. These results reveal the presence of different mechanisms of HbF regulation between patients with sickle cell and healthy individuals.Fetal hemoglobin (HbF) is a determining factor for the development of sickle cell anemia. High HbF levels lower the intensity of symptoms of this disease. HbF levels can vary in patients with sickle cell anemia and individuals without the disease. The purpose of this study was to identify the genetic variants in the G gamma-globin gene promoter that can modulate HbF expression in patients with sickle cell anemia and healthy individuals from Colombia. In total, 413 bp of the G gamma-globin gene promoter were sequenced in 60 patients with sickle cell anemia and 113 healthy individuals. The allelic and genotype frequencies of the identified variants were compared between individuals with low and high HbF for both patients and healthy individuals. In total, we identified 15 variants in both groups, only three of which were shared between patients and healthy individuals. In healthy individuals, sites -16 and -309 (rs112479156) exhibited differences in allele frequencies. The mutant allele of -16 lowered the production of HbF, whereas the mutant allele of -309 increased its production. These results reveal the presence of different mechanisms of HbF regulation between patients with sickle cell and healthy individuals.https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001105965http://orcid.org/0000-0003-1864-2186https://scienti.minciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000002911cristian.fongr@campusucc.edu.cohttps://www.scielo.br/scielo.php?pid=S1415-47572020000400103&script=sci_arttext7Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Odontología, PastoOdontologíaPastoSickle cell anemiaFetal hemoglobinGamma globinRegulation of gene expressionColombiaGenetic variants in the G gamma-globin promoter modulate fetal hemoglobin expression in the Colombian populationArtículos Científicoshttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAtribucióninfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Journal Genetics & molecular biologyAkinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT, Sebastiani P, Chui DHK and Steinberg MH (2011) Fetal hemoglobin in sickle cell anemia. Blood 118:19–27Amrolia PJ, Cunningham JM, Ney P, Nienhuis AW and Jane SM (1995) Identification of two novel regulatory elements within the 5’-untranslated region of the human A gammaglobin gene. J Biol Chem 270:12892–12898Attila G, Yalin S, Tuli A, Yalin E and Aksoy K (2004) Prenatal diagnosis of sickle cell anemia in twin pregnancies and identification by VNTRs. Clin Chim Acta 350:137–142.Bank A (2006) Regulation of human fetal hemoglobin: new players, new complexities. Blood 107:435–443.Barbosa CG, Goncalves-Santos NJ, Souza-Ribeiro SB, MouraNeto JP, Takahashi D, Silva DO, Hurtado-Guerrero AF, Reis MG and Goncalves MS (2010) Promoter region sequence differences in the A and G gamma globin genes of Brazilian sickle cell anemia patients. Braz J Med Biol Res 43:705–711.Barrett JC, Fry B, Maller J and Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265.Basak A and Sankaran VG (2016) Regulation of the fetal hemoglobin silencing factor BCL11A. Ann N Y Acad Sci 1368:25–30.de Vooght KMK, van Wijk R, Ploos van Amstel HK and van Solinge WW (2007) Characterization of the -16C>G sequence variation in the promoters of both HBG1 and HBG2: Convergent evolution of the human -globin genes. Blood Cells Mol Dis 39:70–74Dulmovits BM, Appiah-Kubi AO, Papoin J, Hale J, He M, AlAbed Y, Didier S, Gould M, Husain-Krautter S, Singh SA et al. (2016) Pomalidomide reverses -globin silencing through the transcriptional reprograming of adult hematopoietic progenitors. Blood 127:1481–1492Excoffier L and Lischer HEL (2010) Arlequin suite ver 3.5: a new series of programs to perform population genetics analyzes under Linux and Windows. Mol Ecol Resour 10:564–567.Fong C, Lizarralde-Iragorri MA, Rojas-Gallardo D and Barreto G (2013) Frequency and origin of haplotypes associated with the beta-globin gene cluster in individuals with trait and sickle cell anemia in the Atlantic and Pacific coastal regions of Colombia. Genet Mol Biol 36:494–497.Garner C, Tatu T, Reittie JE, Littlewood T, Darley J, Cervino S, Farrall M, Kelly P, Spector TD and Thein SL (2000) Genetic influences on F cells and other hematologic variables: a twin heritability study. Blood 95:342–346.Gilman JG and Huisman TH (1984) Two independent genetic factors in the beta-globin gene cluster are associated with high G gamma-levels in the HbF of SS patients. Blood 64:452–457.Hebbel RP, Osarogiagbon R and Kaul D (2004) The endothelial biology of sickle cell disease: Inflammation and a chronic vasculopathy. Microcirculation 11:129–151.Hilbe JM (2007) STATISTICA 7: an overview. Am Stat 61:91–94.Jane SM, Ney PA, Vanin EF, Gumucio DL and Nienhuis AW (1992) Identification of a stage selector element in the human gamma-globin gene promoter that fosters preferential interaction with the 5’ HS2 enhancer when in competition with the beta-promoter. EMBO J 11:2961–2969.Li Q, Fang X, Olave I, Han H, Yu M, Xiang P and Stamatoyannopoulos G (2006) Transcriptional potential of the -globin gene is dependent on the CACCC box in a developmental stage-specific manner. Nucleic Acids Res 34:3909–3916.Liu L, Pertsemlidis A, Ding LH, Story MD, Steinberg MH, Sebastiani P, Hoppe C, Ballas SK and Pace BS (2016) A casecontrol genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease. Exp Biol Med 241:706–718.Liu N, Hargreaves VV, Hong J, Kim W, Kurland J, Zhu Q, Sher F, Macias-Trevino C, Rogers J, Yuan GC et al. (2017) Fetal Hemoglobin (HbF) Silencer BCL11A acts through a novel DNA motif in the gamma-globin promoters, symplifying the model for hemoglobin switching. Blood 130:283.Martyn GE, Quinlan KGR and Crossley M (2017) The regulation of human globin promoters by CCAAT box elements and the recruitment of NF-Y. Biochim Biophys Acta Gene Regul Mech 1860:525–536.Menzel S, Jiang J, Silver N, Gallagher J, Cunningham J, Surdulescu G, Lathrop M, Farrall M, Spector TD and Thein SL (2007) The HBS1L-MYB intergenic region on chromosome 6q23.3 influences erythrocyte, platelet, and monocyte counts in humans. Blood 110:3624–3626.Miller SA, Dykes DD and Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215.Ossa H, Aquino J, Pereira R, Ibarra A, Ossa RH, Pérez LA, Granda JD, Lattig MC, Groot H, Fagundes de Carvalho E et al. (2016) Outlining the ancestry landscape of Colombian admixed populations. PLoS One 11:e0164414Pauling L, Itano HA, Singer SJ and Wells IC (1949) Sickle cell anemia a molecular disease. Science 110:543–548.Powars DR, Weiss JN, Chan LS and Schroeder WA (1984) Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia? Blood 63:921–926.Pule GD, Ngo Bitoungui VJ, Chetcha Chemegni B, Kengne AP and Wonkam A (2016) Studies of novel variants associated with Hb F in Sardinians and Tanzanians in sickle cell disease patients from Cameroon. Hemoglobin 40:377–380.Raymond M and Rousset F (1995) An exact test for population differentiation. Evolution 49:1280–1283.Rochette J, Craig JE and Thein SL (1994) Fetal hemoglobin levels in adults. Blood Rev 8:213–224.Singer K, Chernoff AI and Singer L (1951) Studies on Abnormal Hemoglobins: I. Their demonstration in sickle cell anemia and orther hematologic disorders by means of alkali denaturation. Blood 6:413–428.Solovieff N, Milton JN, Hartley SW, Sherva R, Sebastiani P, Dworkis DA, Klings ES, Farrer LA, Garrett ME, AshleyKoch A et al. (2010) Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5’ olfactory receptor gene cluster. Blood 115:1815–1822.Steinberg MH, Lu ZH, Barton FB, Terrin ML, Charache S and Dover GJ (1997) Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea. Blood 89:1078–1088.Thein SL and Menzel S (2009) Discovering the genetics underlying foetal haemoglobin production in adults. Br J Haematol 145:455–467.Traxler EA, Yao Y, Wang YD, Woodard KJ, Kurita R, Nakamura Y, Hughes JR, Hardison RC, Blobel GA, Li C et al. (2016) A genome-editing strategy to treat -hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat Med 22:987–990.Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, Usala G, Busonero F, Maschio A, Albai G et al. (2008) Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad SciUSA 105:1620–1625. 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