RBCC Red Blood Cell Collection

HBG1 [Confidence: high (present in two of the MS resources)]
Hemoglobin subunit gamma-1 (Gamma-1-globin; Hb F Agamma; Hemoglobin gamma-1 chain; Hemoglobin gamma-A chain)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00220706
IPI00220706 Hemoglobin gamma-A and gamma-G chains Gamma chains make up the fetal hemoglobin F, in combination with alpha chains soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight

UniProt P69891
ID HBG1_HUMAN Reviewed; 147 AA.
AC P69891; P02096; P62027; Q549G1; Q8TDA1; Q96FH7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=Hemoglobin subunit gamma-1;
DE AltName: Full=Gamma-1-globin;
DE AltName: Full=Hb F Agamma;
DE AltName: Full=Hemoglobin gamma-1 chain;
DE AltName: Full=Hemoglobin gamma-A chain;
GN Name=HBG1; ORFNames=PRO2979;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7438203; DOI=10.1016/0092-8674(80)90426-2;
RA Slightom J.L., Blechl A.E., Smithies O.;
RT "Human fetal G gamma- and A gamma-globin genes: complete nucleotide
RT sequences suggest that DNA can be exchanged between these duplicated
RT genes.";
RL Cell 21:627-638(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7332928; DOI=10.1016/0092-8674(81)90302-0;
RA Shen S., Slightom J.L., Smithies O.;
RT "A history of the human fetal globin gene duplication.";
RL Cell 26:191-203(1981).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Bi J., Zhou G., Dong C., Zai Y.,
RA Xu W., Gao F., Liu M., He F.;
RT "Functional prediction of the coding sequences of 75 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-76.
RC TISSUE=Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30.
RA Seelig H.-P., Vogel M., Wiemann C., Renz M.;
RT "Homo sapiens HBG1 gene with a 4 bp deletion upstream of the promoter
RT region.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 2-60; 67-77 AND 84-145, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP OXIDATION AT LEU-142.
RX PubMed=7690768;
RA Wilson J.B., Brennan S.O., Allen J., Shaw J.G., Gu L.H., Huisman T.H.;
RT "The M gamma chain of human fetal hemoglobin is an A gamma chain with
RT an in vitro modification of gamma 141 leucine to hydroxyleucine.";
RL J. Chromatogr. A 617:37-42(1993).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF HOMOTETRAMER.
RX PubMed=11514664; DOI=10.1110/ps.11701;
RA Kidd R.D., Baker H.M., Mathews A.J., Brittain T., Baker E.N.;
RT "Oligomerization and ligand binding in a homotetrameric hemoglobin:
RT two high-resolution crystal structures of hemoglobin Bart's
RT (gamma(4)), a marker for alpha-thalassemia.";
RL Protein Sci. 10:1739-1749(2001).
RN [11]
RP ACETYLATION AT GLY-2.
RX PubMed=5554303;
RA Stegink L.D., Meyer P.D., Brummel M.C.;
RT "Human fetal hemoglobin F 1. Acetylation status.";
RL J. Biol. Chem. 246:3001-3007(1971).
RN [12]
RP VARIANT BASKENT THR-129.
RX PubMed=2454900;
RA Altay C., Gurgey A., Wilson J.B., Hu H., Webber B.B., Kutlar F.,
RA Huisman T.H.J.;
RT "Hb F-Baskent or alpha 2A gamma 128(H6)Ala-->Thr.";
RL Hemoglobin 12:87-89(1988).
RN [13]
RP VARIANT BEECH ISLAND ASP-54.
RX PubMed=2417989;
RA Chen S.S., Wilson J.B., Webber B.B., Huisman T.H.J.;
RT "Hb F-Beech Island or alpha 2A gamma 2(53)(D4)Ala-->Asp.";
RL Hemoglobin 9:525-529(1985).
RN [14]
RP VARIANT BONAIRE ARG-40.
RX PubMed=6186637;
RA Nakatsuji T., Headlee M., Lam H., Wilson J.B., Huisman T.H.J.;
RT "Hb F-Bonaire-Ga or alpha 2 A gamma 2 39(C5) Gln replaced by Arg,
RT characterized by high pressure liquid chromatographic and
RT microsequencing procedures.";
RL Hemoglobin 6:599-606(1982).
RN [15]
RP VARIANT CALLUNA ARG-13.
RX PubMed=6199326;
RA Nakatsuji T., Lam H., Huisman T.H.J.;
RT "Hb F-Calluna or alpha 2 gamma 2(12 Thr replaced by Arg; 75Ile;
RT 136Ala) in a Caucasian baby.";
RL Hemoglobin 7:563-566(1983).
RN [16]
RP VARIANT COBB GLY-38.
RX PubMed=2419280;
RA Chen S.S., Webber B.B., Kutlar A., Wilson J.B., Huisman T.H.J.;
RT "Hb F-Cobb or alpha(2)A gamma(2)37(C3)Trp-->Gly.";
RL Hemoglobin 9:617-619(1985).
RN [17]
RP VARIANT DAMMAM ASN-80.
RX PubMed=2411679;
RA Al-Awamy B.H., Niazi G.A., Al-Mouzan M.I., Wilson J.B., Chen S.S.,
RA Webber B.B., Huisman T.H.J.;
RT "Hb F-Dammam or alpha 2A gamma 2(79) (EF3) Asp-->Asn.";
RL Hemoglobin 9:171-173(1985).
RN [18]
RP VARIANT DICKINSON ARG-98.
RX PubMed=4455303; DOI=10.1111/j.1365-2141.1974.tb06670.x;
RA Schneider R.G., Haggard M.E., Gustavson L.P., Brimhall B., Jones R.T.;
RT "Genetic haemoglobin abnormalities in about 9000 Black and 7000 White
RT newborns; haemoglobin F Dickinson (Agamma97His-Arg), a new variant.";
RL Br. J. Haematol. 28:515-524(1974).
RN [19]
RP VARIANT FUKUYAMA ASN-44.
RX PubMed=2467893;
RA Hidaka K., Iuchi I., Nakahara H., Iwakawa G.;
RT "Hb F-Fukuyama or A gamma T43(CD2)Asp-->Asn.";
RL Hemoglobin 13:93-96(1989).
RN [20]
RP VARIANT HULL LYS-122.
RX PubMed=6038320; DOI=10.1136/bmj.3.5564.531;
RA Sacker L.S., Beale D., Black A.J., Huntsman R.G., Lehmann H.,
RA Lorkin P.A.;
RT "Haemoglobin F Hull (gamma-121 glutamic acid-->lysine), homologous
RT with haemoglobins O Arab and O Indonesia.";
RL BMJ 3:531-533(1967).
RN [21]
RP VARIANT IWATA ARG-73.
RX PubMed=6163752;
RA Fuyuno K., Torigoe T., Ohba Y., Matsuoka M., Miyaji T.;
RT "Survey of cord blood hemoglobin in Japan and identification of two
RT new gamma chain variants.";
RL Hemoglobin 5:139-151(1981).
RN [22]
RP VARIANT IZUMI GLY-7.
RX PubMed=6197997; DOI=10.1016/0167-4838(83)90231-5;
RA Wada Y., Hayashi A., Masanori F., Katakuse I., Ichihara T.,
RA Nakabushi H., Matsuo T., Sakurai T., Matsuda H.;
RT "Characterization of a new fetal hemoglobin variant, Hb F Izumi A
RT gamma 6Glu replaced by Gly, by molecular secondary ion mass
RT spectrometry.";
RL Biochim. Biophys. Acta 749:244-248(1983).
RN [23]
RP VARIANT JAMAICA GLU-62.
RX PubMed=5491586; DOI=10.1111/j.1365-2141.1970.tb01450.x;
RA Ahern E.J., Jones R.T., Brimhall B., Gray R.H.;
RT "Haemoglobin F Jamaica (alpha-2 gamma-2 61 Lys leads to Glu; 136
RT Ala).";
RL Br. J. Haematol. 18:369-375(1970).
RN [24]
RP VARIANT JIANGSU MET-135.
RX PubMed=1703137;
RA Plaseska D., Kutlar F., Wilson J.B., Webber B.B., Zeng Y.-T.,
RA Huisman T.H.J.;
RT "Hb F-Jiangsu, the first gamma chain variant with a valine->methionine
RT substitution: alpha 2A gamma 2 134(H12)Val->Met.";
RL Hemoglobin 14:177-183(1990).
RN [25]
RP VARIANT KOTOBUKI GLY-7.
RX PubMed=6175602;
RA Yoshinaka H., Ohba Y., Hattori Y., Matsuoka M., Miyaji T., Fuyuno K.;
RT "A new gamma chain variant, HB F Kotobuki or AI gamma 6 (A3) Glu leads
RT to Gly.";
RL Hemoglobin 6:37-42(1982).
RN [26]
RP VARIANT KUALA LUMPUR GLY-23.
RX PubMed=4765089;
RA Lie-Injo L.E., Wiltshire B.B., Lehmann H.;
RT "Structural identification of haemoglobin F Kuala Lumpur: alpha2
RT gamma2 22(B4)Asp leads to Gly; 136 Ala.";
RL Biochim. Biophys. Acta 322:224-230(1973).
RN [27]
RP VARIANT MACEDONIA-I GLN-3.
RX PubMed=7928382;
RA Plaseska D., Cepreganova-Krstik B., Momirovska A., Efremov G.D.;
RT "Hb F-Macedonia-I or alpha 2A gamma (2)2(NA2)His-->Gln.";
RL Hemoglobin 18:241-245(1994).
RN [28]
RP VARIANT PENDERGRASS ARG-37.
RX PubMed=2581920;
RA Chen S.S., Wilson J.B., Huisman T.H.J.;
RT "Hb F-Pendergrass, an A gamma I variant with a Pro-->Arg substitution
RT at position gamma 36(C2).";
RL Hemoglobin 9:73-77(1985).
RN [29]
RP VARIANT PORDENONE GLN-7.
RX PubMed=6183236;
RA Nakatsuji T., Webber B., Lam H., Wilson J.B., Huisman T.H.J.,
RA Sciarratta G.V., Sansone G., Molaro G.L.;
RT "A new gamma chain variant: Hb F-Pordenone [gamma 6(A3) Glu replaced
RT by Gln: 75ILE: 136ALA].";
RL Hemoglobin 6:397-401(1982).
RN [30]
RP VARIANT SARDINIA THR-76.
RX PubMed=808940;
RA Grifone V., Kamuzora H., Lehmann H., Charlesworth D.;
RT "A new Hb variant: Hb F Sardinia gamma75(E19) isoleucine leads to
RT threonine found in a family with Hb G Philadelphia, beta-chain
RT deficiency and a Lepore-like haemoglobin indistinguishable from Hb
RT A2.";
RL Acta Haematol. 53:347-355(1975).
RN [31]
RP VARIANT SIENA LYS-122.
RX PubMed=6188719;
RA Care A., Marinucci M., Massa A., Maffi D., Sposi N.M., Improta T.,
RA Tentori L.;
RT "Hb F-Siena (alpha 2 a gamma t2 121 (GH4) Glu leads to Lys). A new
RT fetal hemoglobin variant.";
RL Hemoglobin 7:79-83(1983).
RN [32]
RP VARIANT TEXAS-1 LYS-6.
RX PubMed=6019034; DOI=10.1111/j.1365-2141.1967.tb08737.x;
RA Jenkins G.C., Beale D., Black A.J., Huntsman R.G., Lehmann H.;
RT "Haemoglobin F Texas I(alpha-2,gamma-2-5glu-lys): a variant of
RT haemoglobin F.";
RL Br. J. Haematol. 13:252-255(1967).
RN [33]
RP VARIANT VICTORIA JUBILEE TYR-81.
RX PubMed=1138921;
RA Ahern E., Holder W., Ahern V., Serjeant G.R., Serjeant B., Forbes M.,
RA Brimhall B., Jones R.T.;
RT "Haemoglobin F Victoria Jubilee (alpha 2 A gamma 2 80 Asp-Try).";
RL Biochim. Biophys. Acta 393:188-194(1975).
RN [34]
RP VARIANT WOODSTOCK LYS-41.
RX PubMed=1802881;
RA Huisman T.H.J., Kutlar F., Gu L.H.;
RT "Gamma chain abnormalities and gamma-globin gene rearrangements in
RT newborn babies of various populations.";
RL Hemoglobin 15:349-379(1991).
RN [35]
RP VARIANT XIN-SU HIS-74.
RX PubMed=2448269;
RA Ma M., Hu H., Kutlar F., Wilson J.B., Huisman T.H.J.;
RT "Hb F-Xin-Su or A gamma I73(E17)Asp-->His: a new slow-moving fetal
RT hemoglobin variant.";
RL Hemoglobin 11:473-479(1987).
RN [36]
RP VARIANT XINJIANG ARG-26.
RX PubMed=2448268;
RA Hu H., Ma M.;
RT "Hb F-Xinjiang or A gamma T25(B7)Gly-->Arg: a new slow-moving unstable
RT fetal hemoglobin variant.";
RL Hemoglobin 11:465-472(1987).
RN [37]
RP VARIANT YAMAGUCHI ASN-81.
RX PubMed=6198905; DOI=10.1002/ajh.2830160212;
RA Nakatsuji T., Ohba Y., Huisman T.H.J.;
RT "HB F-Yamaguchi (gamma 75Thr, gamma 80Asn, gamma 136Ala) is associated
RT with G gamma-thalassemia.";
RL Am. J. Hematol. 16:189-192(1984).
CC -!- FUNCTION: Gamma chains make up the fetal hemoglobin F, in
CC combination with alpha chains.
CC -!- SUBUNIT: Heterotetramer of two alpha chains and two gamma chains
CC in fetal hemoglobin (Hb F). In the case of deletions affecting one
CC or more of the alpha chains the excess gamma chains form
CC homotetramers that exhibit neither Bohr effect nor heme-heme
CC cooperativity (hemoglobin Bart's).
CC -!- TISSUE SPECIFICITY: Red blood cells.
CC -!- DEVELOPMENTAL STAGE: Expressed until four or five weeks after
CC birth.
CC -!- PTM: Acetylation of Gly-2 converts Hb F to the minor Hb F1.
CC -!- SIMILARITY: Belongs to the globin family.
CC -!- WEB RESOURCE: Name=HbVar; Note=Human hemoglobin variants and
CC thalassemias;
CC URL="http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=directlink&gene;=HBG1";
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DR EMBL; M91036; AAB59429.1; -; Genomic_DNA.
DR EMBL; M91037; AAA58493.1; -; Genomic_DNA.
DR EMBL; V00513; CAA23771.1; -; Genomic_DNA.
DR EMBL; V00514; CAA23772.1; -; Genomic_DNA.
DR EMBL; J00176; AAA52637.1; -; Genomic_DNA.
DR EMBL; U01317; AAA16332.1; -; Genomic_DNA.
DR EMBL; AF130098; AAG35523.1; -; mRNA.
DR EMBL; CH471064; EAW68804.1; -; Genomic_DNA.
DR EMBL; BC010913; AAH10913.1; -; mRNA.
DR EMBL; BC020719; AAH20719.1; -; mRNA.
DR EMBL; AF487523; AAL99545.1; -; Genomic_DNA.
DR PIR; A90803; HGHUA.
DR RefSeq; NP_000550.2; NM_000559.2.
DR UniGene; Hs.702189; -.
DR PDB; 1I3D; X-ray; 1.70 A; A/B=2-147.
DR PDB; 1I3E; X-ray; 1.86 A; A/B=2-147.
DR PDBsum; 1I3D; -.
DR PDBsum; 1I3E; -.
DR ProteinModelPortal; P69891; -.
DR SMR; P69891; 2-147.
DR IntAct; P69891; 1.
DR STRING; 9606.ENSP00000327431; -.
DR PhosphoSite; P69891; -.
DR DMDM; 56749860; -.
DR PaxDb; P69891; -.
DR PRIDE; P69891; -.
DR DNASU; 3047; -.
DR Ensembl; ENST00000330597; ENSP00000327431; ENSG00000213934.
DR GeneID; 3047; -.
DR KEGG; hsa:3047; -.
DR UCSC; uc001mai.1; human.
DR CTD; 3047; -.
DR GeneCards; GC11M005271; -.
DR H-InvDB; HIX0009388; -.
DR HGNC; HGNC:4831; HBG1.
DR MIM; 142200; gene.
DR neXtProt; NX_P69891; -.
DR Orphanet; 231237; Delta-beta thalassemia.
DR Orphanet; 46532; Hereditary persistence of fetal hemoglobin - beta-thalassemia.
DR Orphanet; 251380; Hereditary persistence of fetal hemoglobin - sickle cell disease.
DR PharmGKB; PA29206; -.
DR eggNOG; NOG331950; -.
DR HOGENOM; HOG000036868; -.
DR HOVERGEN; HBG009709; -.
DR KO; K13824; -.
DR OrthoDB; EOG7B8S5H; -.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; HBG1; human.
DR EvolutionaryTrace; P69891; -.
DR GenomeRNAi; 3047; -.
DR NextBio; 12063; -.
DR PRO; PR:P69891; -.
DR ArrayExpress; P69891; -.
DR Bgee; P69891; -.
DR CleanEx; HS_HBG1; -.
DR Genevestigator; P69891; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005833; C:hemoglobin complex; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0019825; F:oxygen binding; IEA:InterPro.
DR GO; GO:0005344; F:oxygen transporter activity; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR Gene3D; 1.10.490.10; -; 1.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like.
DR InterPro; IPR012292; Globin_dom.
DR InterPro; IPR002337; Haemoglobin_b.
DR PANTHER; PTHR11442:SF7; PTHR11442:SF7; 1.
DR Pfam; PF00042; Globin; 1.
DR PRINTS; PR00814; BETAHAEM.
DR SUPFAM; SSF46458; SSF46458; 1.
DR PROSITE; PS01033; GLOBIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome;
KW Direct protein sequencing; Disease mutation; Heme; Iron;
KW Metal-binding; Oxygen transport; Polymorphism; Reference proteome;
KW Transport.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 147 Hemoglobin subunit gamma-1.
FT /FTId=PRO_0000053253.
FT METAL 64 64 Iron (heme distal ligand).
FT METAL 93 93 Iron (heme proximal ligand).
FT SITE 142 142 Susceptible to oxidation; in form M
FT (Probable).
FT MOD_RES 2 2 N-acetylglycine; in form Hb F1.
FT VARIANT 3 3 H -> Q (in Macedonia-I;
FT dbSNP:rs35315638).
FT /FTId=VAR_003124.
FT VARIANT 6 6 E -> K (in Texas-1; dbSNP:rs34427034).
FT /FTId=VAR_003125.
FT VARIANT 7 7 E -> G (in Izumi/Kotobuki;
FT dbSNP:rs34432567).
FT /FTId=VAR_003127.
FT VARIANT 7 7 E -> Q (in Pordenone; dbSNP:rs33924825).
FT /FTId=VAR_003128.
FT VARIANT 13 13 T -> R (in Calluna; dbSNP:rs33992775).
FT /FTId=VAR_003130.
FT VARIANT 23 23 D -> G (in Kuala Lumpur;
FT dbSNP:rs33970907).
FT /FTId=VAR_003135.
FT VARIANT 26 26 G -> R (in Xinjiang; unstable;
FT dbSNP:rs35957832).
FT /FTId=VAR_003138.
FT VARIANT 37 37 P -> R (in Pendergrass;
FT dbSNP:rs41404150).
FT /FTId=VAR_003141.
FT VARIANT 38 38 W -> G (in Cobb; dbSNP:rs35700518).
FT /FTId=VAR_003142.
FT VARIANT 40 40 Q -> R (in Bonaire; dbSNP:rs35977759).
FT /FTId=VAR_003143.
FT VARIANT 41 41 R -> K (in Woodstock; dbSNP:rs33974602).
FT /FTId=VAR_003145.
FT VARIANT 44 44 D -> N (in Fukuyama; dbSNP:rs41475844).
FT /FTId=VAR_003147.
FT VARIANT 54 54 A -> D (in Beech island;
FT dbSNP:rs35746147).
FT /FTId=VAR_003149.
FT VARIANT 62 62 K -> E (in Jamaica; dbSNP:rs34747494).
FT /FTId=VAR_003153.
FT VARIANT 73 73 G -> R (in Iwata).
FT /FTId=VAR_003158.
FT VARIANT 74 74 D -> H (in Xin-su).
FT /FTId=VAR_003160.
FT VARIANT 74 74 D -> N (in Forest Park; associated with
FT T-76).
FT /FTId=VAR_003159.
FT VARIANT 76 76 I -> T (in Sardinia/Forest Park;
FT associated with N-74; dbSNP:rs1061234).
FT /FTId=VAR_003161.
FT VARIANT 80 80 D -> N (in Dammam).
FT /FTId=VAR_003163.
FT VARIANT 81 81 D -> N (in Yamaguchi).
FT /FTId=VAR_003165.
FT VARIANT 81 81 D -> Y (in Victoria jubilee).
FT /FTId=VAR_003164.
FT VARIANT 98 98 H -> R (in Dickinson).
FT /FTId=VAR_003168.
FT VARIANT 122 122 E -> K (in Siena/Hull).
FT /FTId=VAR_003173.
FT VARIANT 129 129 A -> T (in Baskent).
FT /FTId=VAR_003175.
FT VARIANT 135 135 V -> M (in Jiangsu).
FT /FTId=VAR_003177.
FT HELIX 6 17
FT HELIX 21 35
FT HELIX 37 46
FT HELIX 52 57
FT HELIX 59 75
FT HELIX 76 81
FT HELIX 82 85
FT HELIX 87 94
FT TURN 95 97
FT HELIX 101 119
FT HELIX 120 122
FT HELIX 125 142
FT HELIX 144 146
SQ SEQUENCE 147 AA; 16140 MW; 8FCDC3DA1B416DDE CRC64;
MGHFTEEDKA TITSLWGKVN VEDAGGETLG RLLVVYPWTQ RFFDSFGNLS SASAIMGNPK
VKAHGKKVLT SLGDAIKHLD DLKGTFAQLS ELHCDKLHVD PENFKLLGNV LVTVLAIHFG
KEFTPEVQAS WQKMVTAVAS ALSSRYH
//

MIM 142200
*RECORD*
*FIELD* NO
142200
*FIELD* TI
*142200 HEMOGLOBIN, GAMMA A; HBG1
;;HEMOGLOBIN--GAMMA LOCUS, 136 ALANINE
*FIELD* TX
read moreSee 142250. Chang et al. (1978) demonstrated that the 5-prime
untranslated region of the human gamma-globin mRNA contains 57
nucleotides, compared to 41 in alpha and 54 in beta. Both guanosine and
cytidine were found at the 19th nucleotide position from the 5-prime end
of the gamma mRNA. This heterogeneity may reflect differences in the
A-gamma and G-gamma (142250) loci.

Jeffreys (1979) found a restriction enzyme polymorphism of the DNA
intervening sequence of the A-gamma gene. The frequency was estimated at
0.23. Puzzling was the finding of the same polymorphism in the G-gamma
gene. See Slightom et al. (1980) and Shen et al. (1981) for a discussion
of the possible mechanisms for suppression of allelic polymorphism. Gene
conversion is 1 of the 2 classes of known mechanisms that can act on
families of genes to maintain their sequence homology; the other is
unequal crossing-over (Baltimore, 1981). The similarity of the 2
gamma-globin genes (e.g., identical restriction polymorphism in an
intervening sequence) may owe its origin to this mechanism. Slightom et
al. (1980) found that IVS-1 is highly conserved and has 122 bases
between codons 30 and 31; IVS-2, which consists of conserved,
nonconserved and simple sequence DNA and varies in length from 866 to
904 bases, is located between codons 104 and 105. The data of these
authors suggested that gene conversion (intergenic exchanges in cis) is
a frequent event, occurring in the germline. The gene conversion in the
first example found in Smithies' laboratory (Slightom et al., 1980)
involved more than a kilobase of DNA. Smithies and Powers (1986)
referred to examples of much shorter gene conversions in the human fetal
globin gene pair. They suggested that gene conversions are the
consequence of a general mechanism whereby DNA strand invasions enable
chromosomes to find their homologs during meiosis. The model they
suggested had the following elements: In meiosis single-stranded
'feelers' are extruded from many sites along DNA molecules. These
feelers can invade any DNA duplex they encounter and then can scan that
duplex for homologous sequences with which to form a Watson-Crick double
helix. Scanning is halted when a nucleotide sequence is found that can
form a stable double helix. If nearby invasions have also been
successful, a zipper effect will lead to pairing of homologs. If a
stable heteroduplex is formed as a consequence of a related sequence
being found at a nonhomologous chromosomal location, short gene
conversions may result. Gene conversion is more likely to develop
between closely linked genes than between widely separated ones.

Papayannopoulou et al. (1982) demonstrated a humoral factor that induces
switching from gamma-globin to beta-globin in neonatal and adult cells.
Fetal cells are not responsive to the factor. Weinberg et al. (1983)
studied the correlation between gamma-globin and beta-globin synthesis
in cultures of erythroid progenitor cells from newborn infants and
adults. The findings suggested a clonal model for hemoglobin switching.
Lavett (1984) found an extensive stem-loop structure in the
A-gamma-globin promoter region, with intron transcripts from
epsilon-globin, A-gamma-globin, delta-globin and beta-globin showing
sequences complementary to that of the loop. She proposed a model for
globin-switching based on changes in DNA secondary structure and intron
transcript pairing. Melis et al. (1987) presented evidence that the
genes controlling the gamma-to-beta switch are located on human
chromosome 11; whether they operate by a cis- or trans-acting mechanism
was not resolved by the experiments. Melis et al. (1987) pursued the
question of the control of the switch by comparing the chromosomal
composition of hybrids between mouse erythroleukemia (MEL) cells and
human fetal erythroid cells, producing one or the other kind of human
globin, i.e., fetal or adult. Two types of comparison were done. First,
the chromosomal composition of primary hybrids expressing human fetal
globin was compared to that of primary hybrids that had switched to
adult globin production. Second, primary hybrids were subcloned, and
chromosomal composition of subclones expressing fetal globin was
compared to those switched to adult globin formation. The findings
showed that retention of only chromosome 11 is required for expression
of fetal globin and for the subsequent shift from fetal to adult globin
production. The data showed that the gamma-to-beta switch is controlled
by a mechanism that is syntenic with the beta-globin locus. Studies at
the level of chromatin have shown that both the fetal and adult globin
genes are DNase I hypersensitive in fetal erythroid cells, whereas only
the adult globin genes (delta and beta) are DNase I hypersensitive in
adult cells (Groudine et al., 1983).

Foley et al. (2002) demonstrated that synthesis of STAT3-beta (102582)
by erythroleukemia and primary erythroid progenitor cells treated with
IL6 (147620) silences gamma-globin expression. They identified the
STAT3-like binding sequence in the promoters of both A-gamma and G-gamma
hemoglobins.

Trent et al. (1986) identified a Maori family with 4 copies of a
gamma-globin gene on 1 chromosome. A quadrupled gamma gene cluster
detected in a Melanesian by other researchers probably had the same
origin because it had a similar beta gene haplotype for restriction
enzymes. Hemoglobin F levels in adults with quadrupled gamma genes were
normal. See 141749 for description of a nondeletion form of hereditary
persistence of fetal hemoglobin due to point mutation in the promoter
region 5-prime to the A-gamma gene; this form might be called HPFH,
nondeletion type A. In the course of analysis of DNA from 852 Island
Melanesians, Hill et al. (1986) found a high frequency of single- and
triple-gamma-globin genes. All single-gamma genes were A-gamma, all
triple-gamma genes were G-G-A, and the 1 instance of a quadruple-gamma
gene was G-G-G-A (see Trent et al., 1986). The authors favored
intrachromosomal recombination (i.e., between sister chromatids) rather
than interchromosomal recombination. In blacks with G-gamma(beta+) HPFH,
a C-to-G change is found at position -202.

Carver and Kutlar (1995) identified 27 variants due to mutations in the
HBG1 gene, as of January 1995.

- Hemoglobin Gamma Regulatory Region

Hematologic correlations with restriction mapping suggest that a region
of DNA near the 5-prime end of the delta gene may be involved in the
cis-suppression of gamma-globin gene expression in adults (Fritsch et
al., 1979). Putative regulation sequences located between the gamma and
beta loci, which may have a role in regulating the perinatal
gamma-to-beta hemoglobin switch, were also discussed by Jagadeeswaran et
al. (1982) and Ottolenghi and Giglioni (1982). Another segment of DNA
outside the beta-globin gene cluster (142470) regulates F-cell
production in normal persons 'at rest,' under conditions of
erythropoietic stress, and in associated thalassemia and
hemoglobinopathies. Its separateness is indicated by its loose linkage
to the beta globin gene.

The beta-globin locus control region (LCRB; 152424) is a powerful
regulatory element required for high-level globin gene expression. Navas
et al. (2002) generated transgenic mouse lines carrying a beta-globin
locus YAC lacking the locus control region (LCR) to determine if the LCR
is required for globin gene activation. Beta-globin gene expression was
analyzed by RNase protection, but no detectable levels of epsilon-,
gamma-, and beta-globin gene transcripts were produced at any stage of
development. Lack of gamma-globin gene expression was also seen in a
beta-YAC transgenic mouse carrying the gamma-globin promoter mutant that
causes HPFH (142200.0026) and a HS3 core deletion that specifically
abolishes gamma-globin gene expression during definitive erythropoiesis.
The authors concluded that the presence of the LCR is a minimum
requirement for globin gene expression.

Navas et al. (2003) assessed the contribution of the GT6 motif within
HS3 of the LCR on downstream globin gene expression by mutating GT6 in a
beta-globin locus YAC and measuring the activity of beta-globin genes in
GT6-mutated beta-YAC transgenic mice. They found reduced expression of
epsilon- and gamma-globin genes during embryonic erythropoiesis. During
definitive erythropoiesis, gamma-globin gene expression was
significantly reduced while beta-globin gene expression was virtually
indistinguishable from that of wildtype controls. Navas et al. (2003)
concluded that the GT6 motif is required for normal epsilon- and
gamma-globin gene expression during embryonic erythropoiesis and for
gamma-globin gene expression during definitive erythropoiesis in the
fetal liver.

The human gamma-globin gene and its orthologous gene in the galago (a
prosimian primate) evolved from an ancestral epsilon-globin gene (HBE1;
142100). In galago, expression of the gamma gene remained restricted to
the embryonic stage of development, whereas in humans, expression of the
gamma gene was recruited to the fetal stage. To localize the cis
elements responsible for this developmentally distinct regulation, Li et
al. (2004) studied the expression patterns of the human gamma gene
driven by either the human or the galago gamma promoters in transgenic
mice. Gamma gene transcription driven by either promoter reached similar
levels in embryonic erythropoiesis. In adult erythropoiesis, the gamma
gene was silenced when controlled by the galago gamma promoter, but it
was expressed at a high level when it was linked to the human gamma
promoter. By a series of gamma promoter truncations, the sequences
required for the downregulation of the galago gamma-globin gene were
localized to the minimal promoter. Furthermore, by interchanging the
TATA, CCAAT, and CACCC elements between the human and galago minimal
promoters, Li et al. (2004) found that whereas each box made a
developmentally distinct contribution to gamma-globin gene expression,
the CACCC box was largely responsible for the downregulation of the
gamma gene in adult erythropoiesis. The CACCC box is a common element in
the proximal promoters of many housekeeping and lineage-specific genes.
All mutations or deletions of this box impair expression of the affected
genes, suggesting that the CACCC box functions as a transcriptionally
positive element.

GENE THERAPY

Gene therapy for patients with hemoglobin disorders has been hampered by
the inability of retrovirus vectors to transfer globin genes and their
cis-acting regulatory sequences into hematopoietic stem cells without
rearrangement. In addition, the expression from intact globin gene
vectors has been variable in red blood cells due to position effects and
retrovirus silencing. Sabatino et al. (2000) hypothesized that by
substituting the globin gene promoter for the promoter of another gene
expressed in red blood cells, they could generate stable retrovirus
vectors that would express globin at sufficient levels to treat
hemoglobinopathies. They had shown that the human ankyrin (612641) gene
promoter directs position-independent, copy number-dependent expression
of a linked gamma-globin gene in transgenic mice. They presented further
experiments suggesting that constructs between gamma-globin and ankyrin
may be valuable for treating a variety of red cell disorders by gene
replacement therapy, including severe beta-thalassemia.

*FIELD* AV
.0001
HBG1 POLYMORPHISM
HBG1, ILE75THR

In the course of studies of the chemical structure of hemoglobin F in
thalassemia, Ricco et al. (1976) found a new fetal hemoglobin in which
isoleucine at position 75 was replaced by threonine. It was present in
29 of 32 homozygotes in amounts varying from traces to 40% of all Hb F.
It was also found in 40% of normal newborns and premature infants, in a
14-week-old fetus, and in 1 of 3 patients with aplastic anemia and
elevated Hb F. The authors concluded that the synthesis of this gamma
chain is controlled by a separate locus. The T75 gamma chain was thought
to have glycine at position 136. However, Schroeder and Huisman (1979)
stated that the T-gamma chain has alanine in position 136. Huisman et
al. (1981) further described this polymorphism of the A-gamma chain:
A-gamma-I with isoleucine and A-gamma-T with threonine at position 75.
From study of many different populations, Huisman et al. (1985)
presented data on the frequency of the A-gamma gene that has
substitution of threonine for isoleucine at position 75. The frequency
varied from zero in 20 Georgia blacks with CC disease to 24% in AA
persons in Italy.

.0002
HEMOGLOBIN F (BASKENT)
HBG1, ALA128THR

See Altay et al. (1988).

.0003
HEMOGLOBIN F (BEECH ISLAND)
HBG1, ALA53ASP

See Chen et al. (1985).

.0004
HEMOGLOBIN F (BONAIRE)
HBG1, GLN39ARG

See Nakatsuji et al. (1982).

.0005
HEMOGLOBIN F (CALLUNA)
HBG1, THR12ARG

See Nakatsuji et al. (1983).

.0006
HEMOGLOBIN F (COBB)
HBG1, TRP37GLY

See Chen et al. (1985).

.0007
HEMOGLOBIN F (DAMMAM)
HBG1, ASP79ASN

See Al-Awamy et al. (1985).

.0008
HEMOGLOBIN F (DICKINSON)
HBG1, HIS97ARG

See Schneider et al. (1974).

.0009
HEMOGLOBIN F (FOREST PARK)
HBG1, ASP73ASN

Wrightstone, R.: Augusta, Ga.: personal communication, 1986.

.0010
HEMOGLOBIN F (FUKUYAMA)
HBG1, ASP43ASN

See Hidaka et al. (1989).

.0011
HEMOGLOBIN F (IWATA)
HBG1, GLY72ARG

See Fuyuno et al. (1981).

.0012
HEMOGLOBIN F (IZUMI)
HBG1, GLU6GLY

See Wada et al. (1983).

.0013
HEMOGLOBIN F (JAMAICA)
HBG1, LYS61GLU

See Ahern et al. (1970).

.0014
HEMOGLOBIN F (KOTOBUKI)
HBG1, GLU6GLY

This is named for the street in Ube, Japan, where the family lived
(Yoshinaka et al., 1982).

.0015
HEMOGLOBIN F (KUALA LUMPUR)
HBG1, ASP22GLY

See Lie-Injo et al. (1973).

.0016
HEMOGLOBIN F (PENDERGRASS)
HBG1, PRO36ARG

See Chen et al. (1985).

.0017
HEMOGLOBIN F (PORDENONE)
HBG1, GLU6GLN

See Nakatsuji et al. (1982).

.0018
HEMOGLOBIN F (SARDINIA)
HBG1, ILE75THR

See Grifone et al. (1975) and Saglio et al. (1979). The ile75-to-thr
variant is very common and has been found in all ethnic groups, often at
a frequency of more than 0.2. In contrast, the ile75-to-thr mutation in
the HBG2 gene (142250.0039) is rare (Gu et al., 1995).

.0019
HEMOGLOBIN F (SIENA)
HEMOGLOBIN F (HULL)
HBG1, GLU121LYS

The same substitution occurs at the homologous position in the alpha
chain in hemoglobin O (Indonesia) and in the beta chain in hemoglobin O
(Arab). Glutamine is substituted for glutamic acid at beta 121 in
hemoglobin D (Punjab). See Sacker et al. (1967), Care et al. (1983), and
Nakatsuji et al. (1985).

.0020
HEMOGLOBIN F (TEXAS I)
HBG1, GLU5LYS

See Jenkins et al. (1967).

.0021
HEMOGLOBIN F (VICTORIA JUBILEE)
HBG1, ASP80TYR

See Ahern et al. (1975).

.0022
HEMOGLOBIN F (XINJIANG)
HBG1, GLY25ARG

See Hu and Ma (1987). Teng and Ma (1991) observed a second example.

.0023
HEMOGLOBIN F (XIN-SU)
HBG1, ASP73HIS

See Ma et al. (1987).

.0024
HEMOGLOBIN F (YAMAGUCHI)
HBG1, ASP80ASN

See Nakatsuji et al. (1984). Wada et al. (1986) found a frequency of 1
per 2,100 in Japanese neonates.

.0025
HEMOGLOBIN KENYA
HBG1, 1-81/HBD, 86-146

Huisman et al. (1972) described a new hemoglobin in a healthy Kenyan
male. The man was thought to have Hb S in combination with hereditary
persistence of fetal hemoglobin. The abnormal hemoglobin was found to
have a non-alpha chain with characteristics of the gamma chain at the
NH2 end and of the beta chain at the COOH end. The normal Hb F contained
only gamma-G chains. From further studies of the family, Kendall et al.
(1973) concluded that the order of linked genes is gamma-G, gamma-A,
delta, and beta. Crossing-over occurred between residues 81 and 86 of
the gamma and beta chains. Among 7 chromosomes carrying the hemoglobin
Kenya hybrid gene, Lanclos et al. (1987) found only 1 haplotype. Waye et
al. (1992) described a 25-year-old black woman with compound
heterozygosity for Hb S/Hb Kenya and a long history of anemia requiring
transfusions during childhood and adolescence.

.0026
HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN
SARDINIAN HPFH;;
GREEK HPFH
HBG1, G-A, -117

In a Greek HPFH allele, Collins et al. (1985) demonstrated a G-to-A
mutation 117 bp 5-prime to the cap site of the HBG1 gene, just upstream
of the distal CCAAT sequence. Waber et al. (1985) corroborated the
finding that in a particular form of hereditary persistence of fetal
hemoglobin in Greeks (141749) a point mutation (G-to-A) 117 nucleotides
5-prime to the cap site of the A-gamma gene is not a neutral
polymorphism but rather is causative. In this form of HPFH, A-gamma
fetal hemoglobin and beta-globin are synthesized in a 20:80 ratio rather
than the normal 0.5:99.5 ratio. Collins et al. (1985) studied the
expression of this mutation and of a second promoter mutation, C-to-G,
202 nucleotides 5-prime to the cap site of the G-gamma gene. The latter
occurs exclusively in blacks and gives rise to G-gamma-(beta+) HPFH.
Waber et al. (1986) presented evidence that the G-to-A substitution at
nucleotide 117 5-prime to the A-gamma gene is indeed the cause of the
Greek form of A-gamma(beta+) HPFH. In a black family with HPFH, Huang et
al. (1987) found a change from G-to-A at position -117 similar to that
seen in subjects with Greek A-gamma-HPFH. Haplotype analysis supported
the suggestion that the G-to-A substitution occurred as an independent
event in this black family. Superti-Furga et al. (1988) found that the
-117 mutation in the A-gamma gene in the Greek form of HPFH, which is
located immediately upstream of the distal of the 2 CCAAT elements,
interferes with the binding of an erythroid cell-specific factor,
referred to as NF-E. (NF-E stands for nuclear factor, erythroid.) The
findings suggest a possible role of NF-E in the repression of
gamma-globin genes in adult erythroid cells.

Ottolenghi et al. (1988) found a frequency of 0.3% for a new form of
HPFH in northern Sardinia. They showed that the cloned gene had a
substitution of adenine for guanine at position -117 of the
A-gamma-globin gene promoter; the same mutation occurs also in Greek
HPFH, although associated with different restriction polymorphisms. In
Sardinia, another form of HPFH is associated with a -196 C-to-T
substitution in the A-gamma-globin gene promoter (Sardinian
delta-beta-thalassemia; see 142200.0027). To test directly whether the
base substitutions in the promoter regions of the A-gamma-globin gene
can result in an increase in A-gamma-globin gene transcription, Rixon
and Gelinas (1988) studied cosmid clones containing the entire gamma
through beta gene region from persons with Greek-type (G-to-A base
substitution at -117) and Chinese-type (C-to-T base substitution at
-196) A-gamma-HPFH in a transient expression assay. Consistently, the
Greek A-gamma-globin gene produced about 1.4 times as much RNA as the
wildtype gene. No difference was documented between the Chinese-type
promoter and the wildtype promoter. In the study of Sardinian families
with HPFH, Camaschella et al. (1989) found 2 unrelated subjects with
unusually elevated levels of fetal hemoglobin (24%), mostly of the
A-gamma type. Furthermore, hemoglobin A2 was lower than usual (0.8%). By
selective amplification of the HBG1 gene promoter and hybridization to
synthetic oligonucleotides, Camaschella et al. (1989) demonstrated that
these 2 subjects were homozygous for the -117 mutation. One of them was
a 72-year-old woman with 4 healthy children, all heterozygous for HPFH.
Berry et al. (1992) found that when the gamma-globin gene containing the
G-to-A substitution at nucleotide -117 was introduced into mice, there
was persistence of gamma-globin expression at a high level and a
concomitant decrease in beta-globin expression in fetal and adult mice.
They showed, furthermore, that these changes correlated with the loss of
binding of the transcription factor GATA1 to the gamma-globin promoter,
suggesting that it may act as a negative regulator of the gamma-globin
gene in adults. This stands in contrast to the transactivation
properties of GATA1 (Martin and Orkin, 1990; Evans and Felsenfeld,
1991).

.0027
HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN
HBG1, C-T, -196

In a Chinese person who was heterozygous for a nondeletion form of
A-gamma-HPFH (141749), Gelinas et al. (1986) found a cytosine-to-thymine
transition at position -196 of the A-gamma gene promoter. This mutation
at position -196 has been found in unrelated persons with the same
phenotype from Italy and Sardinia. These mutations apparently arose
independently since they are associated with different haplotypes. In
Italians with the A-gamma (beta+) form of HPFH, Waber et al. (1986)
found a C-to-T change at position -196.

In the Sardinian delta-beta-thalassemia, there are 2 mutations: the
mutation in the HBG1 gene at position -196 and the beta-0-thalassemia
mutation at codon 39 of the HBB gene (141900.0312). The mutation at
position -196 is associated with high levels of production of fetal
hemoglobin. The beta-39 nonsense mutation may have gotten onto the -196
chromosome through crossing-over. A chromosome carrying such a double
mutation could be expected to impart selective advantage because the
beta-thalassemia would protect against malaria while the increased
gamma-globin production would ameliorate the severity of the
beta-thalassemia (Pirastu et al., 1987). This chromosome with mutations
in 2 closely linked loci leads to so-called Sardinian nondeletional
delta-beta-thalassemia; more frequently, delta-beta-thalassemia results
from extensive deletions of the beta-globin gene cluster. Loudianos et
al. (1992) sequenced the delta-globin gene (142000) in a case of
Sardinian nondeletional delta-beta-thalassemia and found it to be
entirely normal. They concluded that the deficient function of the
delta-globin gene is probably due to the suppressive effect of the in
cis nondeletional high persistence of fetal hemoglobin mutation in the
HBG1 gene.

.0028
HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN
BRITISH HPFH
HBG1, T-C, -198

Gelinas et al. (1986) referred to a substitution at position -198 in the
A-gamma gene in the British form of HPFH (141749) and to a base
substitution at position -202 in G-gamma HPFH. The -200 region may be
the site of interaction between the gamma-globin gene and trans-acting
elements which turn off the gamma genes in the perinatal period. This
interaction may be weakened by the substitutions found in these forms of
HPFH.

In a British family with nondeletional type of hereditary persistence of
fetal hemoglobin, Tate et al. (1986) identified a -198T-C transition in
the 5-prime region of the HBG2 gene. The family had been reported by
Weatherall et al. (1975). Homozygotes were clinically and
hematologically normal except for increased HbF, ranging from 18 to 21%.
Heterozygotes had HbF of 3.5 to 10%. This has been referred to as the
British form of HPFH.

.0029
HEMOGLOBIN F (JIANGSU)
HBG1, VAL134MET

See Plaseska et al. (1990).

.0030
HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN
HBG1, C-G, -195

In a Brazilian female of Caucasian descent with HPFH (141749), Costa et
al. (1990) found that one chromosome 11 carried a C-to-G mutation at
-195 in the A-gamma promoter. The other chromosome carried a 4-bp
deletion (-225 to -222) which was previously described by Gilman et al.
(1988). The latter mutation appears to cause a decrease in the level of
A-gamma chains. This has been called the Brazilian form of HPFH.

.0031
HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN
HBG1, C-T, -114

In 2 young black males with hereditary persistence of fetal hemoglobin
(141749) who lived in Georgia, Oner et al. (1991) found a C-to-T
substitution at position -114 of the HBG1 gene. Their hematologic data
were completely normal. Both had levels of Hb F of 3 to 5% above normal;
this Hb F contained mainly A-gamma chains. The mutation occurred in the
distal CCAAT box (positions -111 to -115). Fucharoen et al. (1990)
identified the same mutation, C-to-T, at nucleotide -114 of the HBG2
gene (see 142250.0035.)

.0032
HEMOGLOBIN F (CHARLOTTE)
HBG1, ILE75THR AND ALA136GLY

In a black newborn baby, Plaseska et al. (1990) found that about 10% of
the hemoglobin in a cord blood sample contained abnormal hemoglobin with
2 substitutions, threonine for isoleucine-75 and glycine for
alanine-136.

.0033
HEMOGLOBIN F (WOODSTOCK)
HBG1, ARG40LYS

Se Huisman et al. (1991).

.0034
FETAL HEMOGLOBIN, A-GAMMA TYPE, REDUCTION IN
HBG1, 4-BP DEL, -222 TO -225

A mutation that decreases gamma-globin expression has been described; a
4-bp deletion from -222 to -225 (AGCA) was observed to be associated
with reversal of the normal adult 30% G-gamma:70% A-gamma ratio in an
American black family with a beta-zero-thalassemia defect on the cis
chromosome (Gilman et al., 1988) and also in a patient with triplicated
gamma-globin genes and low Hb F (Liu et al., 1988). Harvey et al. (1992)
found the same mutation on one allele in affected members of a large
Australian kindred with nondeletional A-gamma hereditary persistence of
fetal hemoglobin. The other allele was demonstrated to carry the T-to-C
mutation responsible for the British type of HPFH (142200.0028). By
denaturing gradient gel electrophoresis developed for the identification
of point mutations in the 5-prime flanking region of the gamma-globin
genes, Gottardi et al. (1992) unexpectedly found the same 4-bp deletion
at positions -225 to -222 of the HBG1 gene in several samples and showed
that it is a frequent polymorphism; it was present in 15 of 92 alleles
examined.

.0035
HEMOGLOBIN F (MACEDONIA-I)
HBG1, HIS2GLN

In the course of a newborn screening program for hemoglobinopathies in
Macedonia, Plaseska et al. (1994) detected a new HBG1 variant with a
his-to-gln substitution at position 2. The infant was healthy. They
pointed out that histidine occupies the second position of the beta
chain also and that 4 beta-chain variants have a substitution of
histidine at position 2. Hb Okayama has the same his-to-gln substitution
at beta-2; since it shows decreased 2,3-DPG binding, a similar
functional deficit might be expected in Hb F (Macedonia-I). Functional
studies could not be performed, however, because of insufficient
material.

.0036
HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN
HBG1, C-T, -158

Patrinos et al. (1998) described a new type of nondeletional hereditary
persistence of fetal hemoglobin (141749), due to a C-to-T transition at
position -158, relative to the cap site of the HBG1 gene. They
identified the mutation in 3 unrelated adult cases presenting slightly
elevated levels of fetal hemoglobin (2.9 to 5.1%) and normal hematologic
indices. They concluded that the mutation had occurred by 2 independent
gene conversion events in the 3 cases studied, and that the mutation in
1 of the 3 cases occurred recently in the parental germline,
representing the first example of a de novo gene conversion event
identified in humans.

.0037
HEMOGLOBIN F (PORTO TORRES)
HBG1, ALA136SER, ILE75THR

In a blood cord survey for hemoglobinopathies in northern Sardinia,
Pirastru et al. (2004) identified a fetal hemoglobin, designated Hb F
Porto Torres, having 2 substitutions in the HBG1 gene: ala136 to ser
(A136S) and Hb F Sardinia, which is an ile75-to-thr substitution (I75T;
142200.0018). This variant was said to have been the seventh having the
sequence of Hb F Sardinia with an additional mutation.

*FIELD* SA
Chen et al. (1985); Chen et al. (1985); Collins et al. (1985); Efremov
et al. (1979); Lefranc et al. (1981); Nakatsuji et al. (1982); Ottolenghi
et al. (1983); Phillips et al. (1980); Tuan et al. (1979)
*FIELD* RF
1. Ahern, E.; Holder, W.; Ahern, V.; Serjeant, G. R.; Serjeant, B.;
Forbes, M.; Brimhall, B.; Jones, R. T.: Haemoglobin F Victoria Jubilee
(A-gamma 80 asp-to-tyr). Biochim. Biophys. Acta 393: 188-194, 1975.

2. Ahern, E. J.; Jones, R. T.; Brimhall, B.; Gray, R. H.: Haemoglobin
F Jamaica (gamma-A lys-to-glu). Brit. J. Haemat. 18: 369-375, 1970.

3. Al-Awamy, B. H.; Niazi, G. A.; Al-Mouzan, M. I.; Wilson, J. B.;
Chen, S. S.; Webber, B. B.; Huisman, T. H. J.: Hb F-Dammam or A-gamma-79(EF3)asp-to-asn. Hemoglobin 9:
171-173, 1985.

4. Altay, C.; Gurgey, A.; Wilson, J. B.; Hu, H.; Webber, B. B.; Kutlar,
F.; Huisman, T. H. J.: Hb F-Baskent or A-gamma-128 (H6) ala-to-thr. Hemoglobin 12:
87-89, 1988.

5. Baltimore, D.: Gene conversion: some implications for immunoglobulin
genes. Cell 24: 592-594, 1981.

6. Berry, M.; Grosveld, F.; Dillon, N.: A single point mutation is
the cause of the Greek form of hereditary persistence of fetal haemoglobin. Nature 358:
499-502, 1992.

7. Camaschella, C.; Oggiano, L.; Sampietro, M.; Gottardi, E.; Alfarano,
A.; Pistidda, P.; Dore, F.; Taramelli, R.; Ottolenghi, S.; Longinotti,
M.: The homozygous state of G to A -117(alpha)-gamma hereditary persistence
of fetal hemoglobin. Blood 73: 1999-2002, 1989.

8. Care, A.; Marinucci, M.; Massa, A.; Maffi, D.; Sposi, N. M.; Improta,
T.; Tentori, L.: Hb F-Sienna (A-gamma-T 121 (GH4) glu-to-lys): a
new fetal hemoglobin variant. Hemoglobin 7: 79-83, 1983.

9. Carver, M. F. H.; Kutlar, A.: International Hemoglobin Information
Center: variant list. Hemoglobin 19: 37-149, 1995.

10. Chang, J. C.; Poon, R.; Neumann, K. H.; Kan, Y. W.: The nucleotide
sequence of the 5-prime untranslated region of human gamma-globin
mRNA. Nucleic Acids Res. 5: 3515-3522, 1978.

11. Chen, S. S.; Webber, B. B.; Kutlar, A.; Wilson, J. B.; Huisman,
T. H. J.: Hb F-Cobb or A-gamma37(C3)trp-to-gly. Hemoglobin 9: 617-619,
1985.

12. Chen, S. S.; Wilson, J. B.; Huisman, T. H. J.: Hb F-Pendergrass,
an A-gamma-I variant with a pro-to-arg substitution at position gamma36(C2). Hemoglobin 9:
73-77, 1985.

13. Chen, S. S.; Wilson, J. B.; Webber, B. B.; Huisman, T. H. J.:
Hb F-Beech Island or A-gamma-53(D4)ala-to-asp. Hemoglobin 9: 525-529,
1985.

14. Collins, F. S.; Cole, J. L.; Lockwood, W. K.: Expression analysis
of fetal globin gene promoter mutations in hereditary persistence
of fetal hemoglobin. (Abstract) Am. J. Hum. Genet. 37: A149, 1985.

15. Collins, F. S.; Metherall, J. E.; Yamakawa, M.; Pan, J.; Weissman,
S. M.; Forget, B. G.: A point mutation in the A-gamma-globin gene
promoter in Greek hereditary persistence of fetal haemoglobin. Nature 313:
325-326, 1985.

16. Costa, F. F.; Zago, M. A.; Cheng, G.; Nechtman, J. F.; Stoming,
T. A.; Huisman, T. H. J.: The Brazilian type of nondeletional A-gamma-fetal
hemoglobin has a C-to-G substitution at nucleotide -195 of the A-gamma-globin
gene. (Letter) Blood 76: 1896-1897, 1990.

17. Efremov, G. D.; Wilson, J. B.; Huisman, T. H. J.: The chemical
heterogeneity of human hemoglobin F: direct evidence for the existence
of three types of gamma chain, the G-gamma-I, A-gamma-I, and A-gamma-T
chains. Biochim. Biophys. Acta 579: 421-431, 1979.

18. Evans, T.; Felsenfeld, G.: Trans-activation of a globin promoter
in nonerythroid cells. Molec. Cell. Biol. 11: 843-853, 1991.

19. Foley, H. A.; Ofori-Acquah, S. F.; Yoshimura, A.; Critz, S.; Baliga,
B. S.; Pace, B. S.: Stat-3 beta inhibits gamma-globin gene expression
in erythroid cells. J. Biol. Chem. 277: 16211-16219, 2002.

20. Fritsch, E. F.; Lawn, R. M.; Maniatis, T.: Characterisation of
deletions which affect the expression of fetal genes in man. Nature 279:
598-603, 1979.

21. Fucharoen, S.; Shimizu, K.; Fukumaki, Y.: A novel C-to-T transition
within the distal CCAAT motif of the G-gamma-globin gene in the Japanese
HPFH: implication of factor binding in elevated fetal globin expression. Nucleic
Acids Res. 18: 5245-5253, 1990.

22. Fuyuno, K.; Torigoe, T.; Ohba, Y.; Matsuoka, M.; Miyaji, T.:
Survey of cord blood hemoglobin in Japan and identification of two
new gamma chain variants. Hemoglobin 5: 129-151, 1981.

23. Gelinas, R.; Bender, M.; Lotshaw, C.; Waber, P.; Kazazian, H.,
Jr.; Stamatoyannopoulos, G.: Chinese A-gamma fetal hemoglobin: C
to T substitution at position -196 of the A-gamma gene promoter. Blood 67:
1777-1779, 1986.

24. Gilman, J. G.; Johnson, M. E.; Mishima, N.: Four base-pair DNA
deletion in human A-gamma globin-gene promoter associated with low
A-gamma expression in adults. Brit. J. Haemat. 68: 455-458, 1988.

25. Gottardi, E.; Losekoot, M.; Fodde, R.; Saglio, G.; Camaschella,
C.; Bernini, L. F.: Rapid identification by denaturing gradient gel
electrophoresis of mutations in the gamma-globin gene promoters in
non-deletion type HPFH. Brit. J. Haemat. 80: 533-538, 1992.

26. Grifone, V.; Kamuzora, H.; Lehmann, H.; Charlesworth, D.: A new
Hb variant: Hb F Sardinia--gamma 75(E19) isoleucine-to-threonine--found
in a family with Hb G Philadelphia, beta-chain deficiency and a Lepore-like
hemoglobin indistinguishable from Hb A2. Acta Haemat. 53: 347-355,
1975.

27. Groudine, M.; Kohwi-Shigematsu, T.; Gelinas, R.; Stamatoyannopoulos,
G.; Papayannopoulou, T.: Human fetal to adult hemoglobin switching:
changes in chromatin structure of the beta-globin gene locus. Proc.
Nat. Acad. Sci. 80: 7551-7555, 1983.

28. Gu, L.-H.; Oner, C.; Huisman, T. H. J.: The G-gamma-T chain (G-gamma-75
THR; 136 GLY) in Hb F-Charlotte is the product of an A-gamma gene
with a limited gene conversion and that in Hb F-Waynesboro of a mutated
G-gamma gene. Hemoglobin 19: 413-418, 1995.

29. Harvey, M. P.; Motum, P.; Lindeman, R.; Trent, R. J.: An A-gamma
globin promoter (four base-pair deletion) mutant shows linked polymorphic
changes throughout the A-gamma gene. Exp. Hemat. 20: 320-323, 1992.

30. Hidaka, K.; Iuchi, I.; Nakahara, H.; Iwakawa, G.: Hb F-Fukuyama
or A-gamma-43 (CD2) asp-to-asn. Hemoglobin 13: 93-96, 1989.

31. Hill, A. V. S.; Bowden, D. K.; Weatherall, D. J.; Clegg, J. B.
: Chromosomes with one, two, three, and four fetal globin genes: molecular
and hematologic analysis. Blood 67: 1611-1618, 1986.

32. Hu, H.; Ma, M.: Hb F-Xinjiang or A-gamma-T-25 (B7) gly-to-arg:
a new slow-moving unstable fetal hemoglobin variant. Hemoglobin 11:
465-472, 1987.

33. Huang, H. J.; Stoming, T. A.; Harris, H. F.; Kutlar, F.; Huisman,
T. H. J.: The Greek A-gamma-beta+/HPFH observed in a large black
family. Am. J. Hemat. 25: 401-408, 1987.

34. Huisman, T. H. J.; Altay, C.; Webber, B.; Reese, A. L.; Gravely,
M. E.; Okonjo, K.; Wilson, J. B.: Quantitation of three types of
gamma chain of Hb F by high pressure liquid chromatography; application
of this method to the Hb F of patients with sickle cell anemia or
the S-HPFH condition. Blood 57: 75-82, 1981.

35. Huisman, T. H. J.; Kutlar, F.; Gu, L.-H.: Gamma chain abnormalities
and gamma-globin gene rearrangements in newborn babies of various
populations. Hemoglobin 15: 349-379, 1991.

36. Huisman, T. H. J.; Kutlar, F.; Nakatsuji, T.; Bruce-Tagoe, A.;
Kilinc, Y.; Cauchi, M. N.; Garcia, C. R.: The frequency of the gamma
chain variant A-gamma-T in different populations, and its use in evaluating
gamma gene expression in association with thalassemia. Hum. Genet. 71:
127-133, 1985.

37. Huisman, T. H. J.; Wrightstone, R. N.; Wilson, J. B.; Schroeder,
W. A.; Kendall, A. G.: Hemoglobin Kenya, the product of fusion of
gamma and beta polypeptide chains. Arch. Biochem. Biophys. 153:
850-853, 1972.

38. Jagadeeswaran, P.; Tuan, D.; Forget, B. G.; Weissman, S. M.:
A gene deletion ending at the midpoint of a repetitive DNA sequence
in one form of hereditary persistence of fetal haemoglobin. Nature 296:
469-470, 1982.

39. Jeffreys, A. J.: DNA sequence variants in the G-gamma, A-gamma,
delta and beta globin genes of man. Cell 18: 1-10, 1979.

40. Jenkins, G. C.; Beale, D.; Black, A. J.; Huntsman, R. G.; Lehmann,
H.: Haemoglobin F Texas 1 (gamma 5 glu-to-lys): a variant of haemoglobin
F. Brit. J. Haemat. 13: 252-255, 1967.

41. Kendall, A. G.; Ojwang, P. J.; Schroeder, W. A.; Huisman, T. H.
J.: Hemoglobin Kenya, the product of a gamma-beta fusion gene: studies
of the family. Am. J. Hum. Genet. 25: 548-563, 1973.

42. Lanclos, K. D.; Patterson, J.; Efremov, G. D.; Wong, S. C.; Villegas,
A.; Ojwang, P. J.; Wilson, J. B.; Kutlar, F.; Huisman, T. H. J.:
Characterization of chromosomes with hybrid genes for Hb Lepore-Washington,
Hb Lepore-Baltimore, Hb P-Nilotic, and Hb Kenya. Hum. Genet. 77:
40-45, 1987.

43. Lavett, D. K.: Secondary structure and intron-promoter homology
in globin-switching. Am. J. Hum. Genet. 36: 338-345, 1984.

44. Lefranc, M.-P.; Lefranc, G.; Farhat, M.; Jmour, R.; Boukef, K.;
Beuzard, Y.; Galacteros, F.; Rosa, J.: Frequency of human (A)gamma(75Thr)
globin chain in a population from Tunisia. Hum. Genet. 59: 89-91,
1981.

45. Li, Q.; Fang, X.; Han, H.; Stamatoyannopoulos, G.: The minimal
promoter plays a major role in silencing of the galago gamma-globin
gene in adult erythropoiesis. Proc. Nat. Acad. Sci. 101: 8096-8101,
2004.

46. Lie-Injo, L. E.; Wiltshire, B. B.; Lehmann, H.: Structural identification
of haemoglobin F (Kuala Lumpur): gamma 22 (B4) asp-to-gly; 136 ala. Biochim.
Biophys. Acta 322: 224-230, 1973.

47. Liu, J. Z.; Gilman, J. G.; Cao, Q.; Bakioglu, I.; Huisman, T.
H. J.: Four categories of gamma-globin gene triplications: DNA sequence
comparison of low G-gamma and high G-gamma triplications. Blood 72:
480-484, 1988.

48. Loudianos, G.; Moi, P.; Lavinha, J.; Galanello, R.; Cao, A.; Pirastu,
M.: Normal delta-globin gene sequences in Sardinian nondeletional
delta-beta-thalassemia. Hemoglobin 16: 503-509, 1992.

49. Ma, M.; Hu, H.; Kutlar, F.; Wilson, J. B.; Huisman, T. H. J.:
Hb F-Xin-Su or A-gamma-I-73 (E17) asp-to-his: a new slow-moving fetal
hemoglobin variant. Hemoglobin 11: 473-479, 1987.

50. Martin, D. I. K.; Orkin, S. H.: Transcriptional activation and
DNA binding by the erythroid factor GF-1/NF-E1/Eryf 1. Genes Dev. 4:
1886-1898, 1990.

51. Melis, M.; Demopulos, G.; Najfeld, V.; Zhang, J.; Brice, M.; Papayannopoulou,
T.; Stamatoyannopoulos, G.: A chromosome 11-linked determinant controls
fetal globin expression and the fetal-to-adult globin switch. Proc.
Nat. Acad. Sci. 84: 8105-8109, 1987.

52. Nakatsuji, T.; Burnley, M. S.; Huisman, T. H. J.: Fetal hemoglobin
variants identified in adults through restriction endonuclease gene
mapping methodology. Blood 66: 803-807, 1985.

53. Nakatsuji, T.; Headlee, M.; Lam, H.; Wilson, J. B.; Huisman, T.
H. J.: Hb F-Bonaire-Ga or A-gamma (C5) gln-to-arg, characterized
by high pressure liquid chromatographic and microsequencing procedures. Hemoglobin 6:
599-606, 1982.

54. Nakatsuji, T.; Lam, H.; Huisman, T. H. J.: Hb F-Calluna or A-gamma
(12 thr-to-arg; 75 Ile; 136 ala) in a Caucasian baby. Hemoglobin 7:
563-566, 1983.

55. Nakatsuji, T.; Ohba, Y.; Huisman, T. H. J.: Hb F-Yamaguchi (gamma-75thr,
gamma-80asn, gamma-136ala) is associated with G-gamma-thalassemia. Am.
J. Hemat. 16: 189-192, 1984.

56. Nakatsuji, T.; Webber, B.; Lam, H.; Wilson, J. B.; Huisman, T.
H. J.; Sciarratta, G. V.; Sansone, G.; Molaro, G. L.: A new gamma
chain variant: Hb F-Pordenone (A-gamma 6) glu-to-gln: 75 ile: 136
ala). Hemoglobin 6: 397-401, 1982.

57. Navas, P. A.; Li, Q.; Peterson, K. R.; Swank, R. A.; Rohde, A.;
Roy, J.; Stamatoyannopoulos, G.: Activation of the beta-like globin
genes in transgenic mice is dependent on the presence of the beta-locus
control region. Hum. Molec. Genet. 11: 893-903, 2002.

58. Navas, P. A.; Swank, R. A.; Yu, M.; Peterson, K. R.; Stamatoyannopoulos,
G.: Mutation of a transcriptional motif of a distant regulatory element
reduces the expression of embryonic and fetal globin genes. Hum.
Molec. Genet. 12: 2941-2948, 2003.

59. Oner, R.; Kutlar, F.; Gu, L.-H.; Huisman, T. H. J.: The Georgia
type of nondeletional hereditary persistence of fetal hemoglobin has
a C-to-T mutation at nucleotide -114 of the A-gamma-globin gene. Blood 77:
1124-1128, 1991.

60. Ottolenghi, S.; Camaschella, C.; Comi, P.; Giglioni, B.; Longinotti,
M.; Oggiano, L.; Dore, F.; Sciarratta, G.; Ivaldi, G.; Saglio, G.;
Serra, A.; Loi, A.; Pirastu, M.: A frequent A-gamma-hereditary persistence
of fetal hemoglobin in northern Sardinia: its molecular basis and
hematologic phenotype in heterozygotes and compound heterozygotes
with beta-thalassemia. Hum. Genet. 79: 13-17, 1988.

61. Ottolenghi, S.; Giglioni, B.: The deletion in a type of gamma-0-beta-0-thalassemia
begins in an inverted Alu I repeat. Nature 300: 770-771, 1982.

62. Ottolenghi, S.; Giglioni, B.; Taramelli, R.; Comi, P.; Mazza,
U.; Saglio, G.; Izzo, P.; Cao, A.; Galanello, R.; Gimferrer, E.; Baiget,
M.; Gianni, A. M.: Molecular comparison of delta-beta-thalassemia
and hereditary persistence of fetal hemoglobin DNAs: evidence of a
regulatory area? Proc. Nat. Acad. Sci. 79: 2347-2351, 1983.

63. Papayannopoulou, T.; Kurachi, S.; Nakamoto, B.; Zanjani, E. D.;
Stamatoyannopoulos, G.: Hemoglobin switching in culture: evidence
for a humoral factor that induces switching in adult and neonatal
but not fetal erythroid cells. Proc. Nat. Acad. Sci. 79: 6579-6583,
1982.

64. Patrinos, G. P.; Kollia, P.; Loutradi-Anagnostou, A.; Loukopoulos,
D.; Papadakis, M. N.: The Cretan type of non-deletional hereditary
persistence of fetal hemoglobin (A-gamma-158C-T) results from two
independent gene conversion events. Hum. Genet. 102: 629-634, 1998.

65. Phillips, J. A., III; Panny, S. R.; Kazazian, H. H., Jr.; Boehm,
C. D.; Scott, A. F.; Smith, K. D.: Prenatal diagnosis of sickle cell
anemia by restriction endonuclease analysis: HindIII polymorphisms
in gamma-globin genes extend test applicability. Proc. Nat. Acad.
Sci. 77: 2853-2856, 1980.

66. Pirastru, M.; Manca, L.; Palici di Suni, M.; Speziga, S. M.; Masala,
B.: Hb F-Porto Torres [A-gamma-75(E19)ile-to-thr, 136(H14)ala-to-ser]:
a novel variant of the A-gamma chain having two substitutions, one
being that of Hb F-Sardinia. Hemoglobin 28: 297-303, 2004.

67. Pirastu, M.; Galanello, R.; Doherty, M. A.; Tuveri, T.; Cao, A.;
Kan, Y. W.: The same beta-globin gene mutation is present on nine
different beta-thalassemia chromosomes in a Sardinian population. Proc.
Nat. Acad. Sci. 84: 2882-2885, 1987.

68. Plaseska, D.; Cepreganova-Krstik, B.; Momirovska, A.; Efremov,
G. D.: Hb F-Macedonia-I or A-gamma-2(NA2)his-to-gln. Hemoglobin 18:
241-245, 1994.

69. Plaseska, D.; Kutlar, F.; Wilson, J. B.; Fei, Y. J.; Huisman,
T. H. J.: Hb F-Charlotte, an A-gamma variant with a threonine residue
in position gamma-75 and a glycine residue in position gamma-136. Hemoglobin 14:
617-625, 1990.

70. Plaseska, D.; Kutlar, F.; Wilson, J. B.; Webber, B. B.; Zeng,
Y.-T.; Huisman, T. H. J.: Hb F-Jiangsu, the first gamma chain variant
with a valine-to-methionine substitution: gamma(2)134(H12)val-to-met. Hemoglobin 14:
177-183, 1990.

71. Ricco, G.; Mazza, U.; Turi, R. M.; Pich, P. G.; Camaschella, C.;
Saglio, G.; Bernini, L. F.: Significance of a new type of human fetal
hemoglobin carrying a replacement isoleucine-to-threonine at position
75 (E19) of the gamma chain. Hum. Genet. 32: 305-313, 1976.

72. Rixon, M. W.; Gelinas, R. E.: A fetal globin gene mutation in
A-gamma nondeletion hereditary persistence of fetal hemoglobin increases
promoter strength in a nonerythroid cell. Molec. Cell. Biol. 8:
713-721, 1988.

73. Sabatino, D. E.; Seidel, N. E.; Aviles-Mendoza, G. J.; Cline,
A. P.; Anderson, S. M.; Gallagher, P. G.; Bodine, D. M.: Long-term
expression of gamma-globin mRNA in mouse erythrocytes from retrovirus
vectors containing the human gamma-globin gene fused to the ankyrin-1
promoter. Proc. Nat. Acad. Sci. 97: 13294-13299, 2000.

74. Sacker, L. S.; Beale, D.; Black, A. J.; Huntsman, R. G.; Lehmann,
H.; Lorkin, P. A.: Haemoglobin F Hull (gamma 121 glutamic acid to
lysine), homologous with Haemoglobins O Arab and O Indonesia. Brit.
Med. J. 3: 531-533, 1967.

75. Saglio, G.; Ricco, G.; Mazza, U.; Camaschella, C.; Pich, P. G.;
Gianni, A. M.; Gianazza, E.; Righetti, P. G.; Giglioni, B.; Momi,
P.; Gusmeroli, M.; Ottolenghi, S.: Human T-gamma globin chain is
a variant of A-gamma chain (A-gamma-Sardinia). Proc. Nat. Acad. Sci. 76:
3420-3424, 1979.

76. Schneider, R. G.; Haggard, M. E.; Gustavson, L. P.; Brimhall,
B.; Jones, R. T.: Genetic hemoglobin abnormalities in about 9000
black and 7000 white newborns; hemoglobin F (Dickinson) (A gamma 97
his-to-arg), a new variant. Brit. J. Haemat. 28: 515-524, 1974.

77. Schroeder, W. A.; Huisman, T. H. J.: Human gamma chains: structural
features.In: Stamatoyannopoulos, G.; Nienhuis, A. W.: Cellular and
Molecular Regulation of Hemoglobin Switching. New York: Grune and
Stratton (pub.) 1979. Pp. 28-45.

78. Shen, S.-H.; Slightom, J. L.; Smithies, O.: A history of the
human fetal globin gene duplication. Cell 26: 191-203, 1981.

79. Slightom, J. L.; Blechl, A. E.; Smithies, O.: Human fetal G-gamma
and A-gamma globin genes: complete nucleotide sequences suggest that
DNA can be exchanged between these duplicated genes. Cell 21: 627-638,
1980.

80. Smithies, O.; Powers, P. A.: Gene conversions and their relation
to homologous chromosome pairing. Phil. Trans. Roy. Soc. London B 312:
291-302, 1986.

81. Superti-Furga, G.; Barberis, A.; Schaffner, G.; Busslinger, M.
: The -117 mutation in Greek HPFH affects the binding of three nuclear
factors to the CCAAT region of the gamma-globin gene. EMBO J. 7:
3099-3107, 1988.

82. Tate, V. E.; Wood, W. G.; Weatherall, D. J.: The British form
of hereditary persistence of fetal hemoglobin results from a single
base mutation adjacent to an S1 hypersensitive site 5-prime to the
A-gamma-globin gene. Blood 68: 1389-1393, 1986.

83. Teng, K.; Ma, M. S.: Hb F-Xinjiang or A-gamma-T(2)25(B7)gly-to-arg
identified by reversed phase HPLC: second observation. Hemoglobin 15:
545-547, 1991.

84. Trent, R. J.; Mickleson, K. N. P.; Wilkinson, T.; Yakas, J.; Dixon,
M. W.; Hill, P. J.; Kronenberg, H.: Globin genes in Polynesians have
many rearrangements including a recently described gamma-gamma-gamma-gamma/. Am.
J. Hum. Genet. 39: 350-360, 1986.

85. Tuan, D.; Biro, P. A.; DeRiel, J. K.; Lazarus, H.; Forget, B.
G.: Restriction endonuclease mapping of the human gamma globin gene
loci. Nucleic Acids Res. 6: 2519-2544, 1979.

86. Waber, P. G.; Bender, M. A.; Gelinas, R. E.; Kattamis, C.; Karaklis,
A.; Sofroniadou, K.; Stamatoyannopoulos, G.; Collins, F. S.; Forget,
B. G.; Kazazian, H. H., Jr.: Concordance of a point mutation 5-prime
to the A-gamma-globin gene with A-gamma(beta+) hereditary persistence
of fetal hemoglobin in Greeks. Blood 67: 551-554, 1986.

87. Waber, P. G.; Kazazian, H. H.; Gelinas, R. E.; Forget, B. G.;
Collins, F. S.: Concordance of a point mutation 5-prime to the A-gamma
gene with A-gamma-beta+ hereditary persistence of fetal hemoglobin
(HPFH) in Greeks. (Abstract) Am. J. Hum. Genet. 37: A180, 1985.

88. Wada, Y.; Fujita, T.; Kidoguchi, K.; Hayashi, A.: Fetal hemoglobin
variants in 80,000 Japanese neonates: high prevalence of Hb F Yamaguchi
(A-gamma-T 80asp-to-asn). Hum. Genet. 72: 196-202, 1986.

89. Wada, Y.; Hayashi, A.; Masanori, F.; Katakuse, I.; Ichihara, T.;
Nakabushi, H.; Matsuo, T.; Sakurai, T.; Matsuda, H.: Characterization
of a new fetal hemoglobin variant, Hb F Izumi (A-gamma-6glu-to-gly),
by molecular secondary ion mass spectrometry. Biochim. Biophys. Acta 749:
244-248, 1983.

90. Waye, J. S.; Cai, S.-P.; Eng, B.; Chui, D. H. K.; Francombe, W.
H.: Clinical course and molecular characterization of a compound
heterozygote for sickle hemoglobin and hemoglobin Kenya. Am. J. Hemat. 41:
289-291, 1992.

91. Weatherall, D. J.; Cartner, R.; Clegg, J. B.; Wood, W. G.; Macrae,
I. A.; Mackenzie, A.: A form of hereditary persistence of fetal haemoglobin
characterized by uneven cellular distribution of haemoglobin F and
the production of haemoglobins A and A2 in homozygotes. Brit. J.
Haemat. 29: 205-220, 1975.

92. Weinberg, R. S.; Goldberg, J. D.; Schofield, J. M.; Lenes, A.
L.; Styczynski, R.; Alter, B. P.: Switch from fetal to adult hemoglobin
is associated with a change in progenitor cell population. J. Clin.
Invest. 71: 785-794, 1983.

93. Yoshinaka, H.; Ohba, Y.; Hattori, Y.; Matsuoka, M.; Miyaji, T.;
Fuyuno, K.: A new gamma chain variant, HB F Kotobuki or A-gamma-I-6
(A3) glu-to-gly. Hemoglobin 6: 37-42, 1982.

*FIELD* CN
Cassandra L. Kniffin - updated: 6/3/2009
George E. Tiller - updated: 1/23/2006
Victor A. McKusick - updated: 3/3/2005
Victor A. McKusick - updated: 7/8/2004
George E. Tiller - updated: 12/17/2002
Patricia A. Hartz - updated: 5/15/2002
Victor A. McKusick - updated: 1/3/2001
Victor A. McKusick - updated: 8/3/1998

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
alopez: 07/15/2011
carol: 5/19/2011
carol: 6/4/2009
ckniffin: 6/3/2009
carol: 2/26/2009
wwang: 1/23/2006
tkritzer: 3/11/2005
terry: 3/3/2005
tkritzer: 7/15/2004
terry: 7/8/2004
cwells: 12/17/2002
carol: 5/15/2002
mcapotos: 1/10/2001
terry: 1/3/2001
carol: 4/17/2000
carol: 9/8/1999
dkim: 12/15/1998
carol: 8/4/1998
terry: 8/3/1998
alopez: 8/1/1997
alopez: 7/31/1997
mark: 7/21/1997
mark: 2/26/1996
terry: 2/19/1996
carol: 7/9/1995
mark: 6/4/1995
mimadm: 9/24/1994
terry: 8/25/1994
pfoster: 4/20/1994
carol: 11/12/1993