LOCUS AAA16332.1 147 aa PRT HUM 16-OCT-2008
DEFINITION Homo sapiens A-gamma globin protein.
ACCESSION U01317-3
PROTEIN_ID AAA16332.1
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (bases 62409 to 62631; 63482 to 63610)
AUTHORS Marotta,C.A., Forget,B.G., Weissman,S.M., Verma,I.M.,
McCaffrey,R.P. and Baltimore,D.
TITLE Nucleotide sequences of human globin messenger RNA
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 71 (6), 2300-2304 (1974)
PUBMED 4135409
REFERENCE 2 (bases 63602 to 63646)
AUTHORS Forget,B.G., Marotta,C.A., Weissman,S.M. and Cohen-Solal,M.
TITLE Nucleotide sequences of the 3'-terminal untranslated region of
messenger RNA for human beta globin chain
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 72 (9), 3614-3618 (1975)
PUBMED 1059150
REFERENCE 3 (bases 63593 to 63626)
AUTHORS Proudfoot,N.J. and Brownlee,G.G.
TITLE Nucleotide sequences of globin messenger RNA
JOURNAL Br. Med. Bull. 32 (3), 251-256 (1976)
PUBMED 788834
REFERENCE 4 (bases 63673 to 63743)
AUTHORS Proudfoot,N.J. and Longley,J.I.
TITLE The 3' terminal sequences of human alpha and beta globin messenger
RNAs: comparison with rabbit globin messenger RNA
JOURNAL Cell 9 (4 PT 2), 733-746 (1976)
PUBMED 1035137
REFERENCE 5 (sites)
AUTHORS Proudfoot,N.J. and Brownlee,G.G.
TITLE 3' non-coding region sequences in eukaryotic messenger RNA
JOURNAL Nature 263 (5574), 211-214 (1976)
PUBMED 822353
REFERENCE 6 (bases 63596 to 63743)
AUTHORS Proudfoot,N.J.
TITLE Complete 3' noncoding region sequences of rabbit and human
beta-globin messenger RNAs
JOURNAL Cell 10 (4), 559-570 (1977)
PUBMED 67897
REFERENCE 7 (bases 62137 to 62193)
AUTHORS Baralle,F.
TITLE Complete nucleotide sequence of the 5' noncoding region of human
alpha-and beta-globin mRNA
JOURNAL Cell 12 (4), 1085-1095 (1977)
PUBMED 597858
REFERENCE 8 (sites)
AUTHORS Marotta,C.A., Forget,B.G., Cohne-Solal,M., Wilson,J.T. and
Weissman,S.M.
TITLE Human beta-globin messenger RNA. I. Nucleotide sequences derived
from complementary RNA
JOURNAL J. Biol. Chem. 252 (14), 5019-5031 (1977)
PUBMED 873928
REFERENCE 9 (bases 62187 to 63610)
AUTHORS Cohen-Solal,M., Forget,B.G., Prensky,W., Marotta,C.A. and
Weissman,S.M.
TITLE Human beta-globin messenger RNA. II. nucleotide sequences derived
from 125I-labeled globin messenger RNA
JOURNAL J. Biol. Chem. 252 (14), 5032-5039 (1977)
PUBMED 318159
REFERENCE 10 (bases 54790 to 54881; 62409 to 62631; 63482 to 63715)
AUTHORS Marotta,C.A., Wilson,J.T., Forget,B.G. and Weissman,S.M.
TITLE Human beta-globin messenger RNA. III. Nucleotide sequences derived
from complementary DNA
JOURNAL J. Biol. Chem. 252 (14), 5040-5053 (1977)
PUBMED 68958
REFERENCE 11 (bases 62137 to 62189)
AUTHORS Chang,J.C., Temple,G.F., Poon,R., Neumann,K.H. and Kan,Y.W.
TITLE The nucleotide sequences of the untranslated 5' regions of human
alpha- and beta-globin mRNAs
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 74 (11), 5145-5149 (1977)
PUBMED 270752
REFERENCE 12 (bases 56103 to 56184)
AUTHORS Lawn,R.M., Fritsch,E.F., Parker,R.C., Blake,G. and Maniatis,T.
TITLE The isolation and characterization of linked delta- and beta-globin
genes from a cloned library of human DNA
JOURNAL Cell 15 (4), 1157-1174 (1978)
PUBMED 728996
REFERENCE 13 (bases 35854 to 35946; 63482 to 63531)
AUTHORS Little,P., Curtis,P., Coutelle,C., Van den Berg,J., Dalgleish,R.,
Malcolm,S., Courtney,M., Westaway,D. and Williamson,R.
TITLE Isolation and partial sequence of recombinant plasmids containing
human alpha-, beta- and gamma-globin cDNA fragments
JOURNAL Nature 273 (5664), 640-643 (1978)
PUBMED 318161
REFERENCE 14 (bases 62187 to 63742)
AUTHORS Wilson,J.T., Wilson,L.B., deRiel,J.K., Villa-komaroff,L.,
Efstratiadis,A., Forget,B.G. and Weissman,S.M.
TITLE Insertion of synthetic copies of human globin genes into bacterial
plasmids
JOURNAL Nucleic Acids Res. 5 (2), 563-581 (1978)
PUBMED 345245
REFERENCE 15 (bases 34478 to 34563; 39414 to 39499)
AUTHORS Chang,J.C., Poon,R., Neumann,K.H. and Kan,Y.W.
TITLE The nucleotide sequence of the 5' untranslated region of human
gamma-globin mRNA
JOURNAL Nucleic Acids Res. 5 (10), 3515-3522 (1978)
PUBMED 318162
REFERENCE 16 (bases 40839 to 40985)
AUTHORS Poon,R., Kan,Y.W. and Boyer,H.W.
TITLE Sequence of the 3'-noncoding and adjacent coding regions of human
gamma-globin mRNA
JOURNAL Nucleic Acids Res. 5 (12), 4625-4630 (1978)
PUBMED 318163
REFERENCE 17 (bases 35826 to 35907; 40742 to 40823)
AUTHORS Smithies,O., Blechl,A.E., Denniston-Thompson,K., Newell,N.,
Richards,J.E., Slightom,J.L., Tucker,P.W. and Blattner,F.R.
TITLE Cloning human fetal gamma globin and mouse alpha-type globin DNA:
characterization and partial sequencing
JOURNAL Science 202 (4374), 1284-1289 (1978)
PUBMED 725604
REFERENCE 18 (bases 34478 to 34536; 62137 to 62192; 63608 to 63742)
AUTHORS Kan,Y.W., Chang,C.S. and Poon,R.
TITLE Nucleotide sequences of the untranslated 5' and 3' regions of human
alpha-, beta-, and gamma-globin mRNAS
JOURNAL (in) Stamatoyannopoulos,G. and Newhouse,A.W. (Eds.);
CELLULAR AND MOLECULAR REGULATION OF HEMOGLOBIN SWITCHING: 0-0;
Grune and Stratton, New York (1979) In press
REFERENCE 19 (sites)
AUTHORS Chang,J.C. and Kan,Y.W.
TITLE beta 0 thalassemia, a nonsense mutation in man
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 76 (6), 2886-2889 (1979)
PUBMED 88735
REFERENCE 20 (bases 19846 to 19965)
AUTHORS Proudfoot,N.J. and Baralle,F.E.
TITLE Molecular cloning of human epsilon-globin gene
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 76 (11), 5435-5439 (1979)
PUBMED 160554
REFERENCE 21 (sites)
AUTHORS Chang,J.C., Kan,Y.W., Trecartin,R.F. and Temple,G.F.
TITLE Nonsense mutation as a cause of beta 0 thalassemia
JOURNAL Ann. N. Y. Acad. Sci. 344, 113-119 (1980)
PUBMED 6985475
REFERENCE 22 (sites)
AUTHORS Fritsch,E.F., Lawn,R.M. and Maniatis,T.
TITLE Molecular cloning and characterization of the human beta-like
globin gene cluster
JOURNAL Cell 19 (4), 959-972 (1980)
PUBMED 6155216
REFERENCE 23 (bases 19462 to 21741)
AUTHORS Baralle,F.E., Shoulders,C.C. and Proudfoot,N.J.
TITLE The primary structure of the human epsilon-globin gene
JOURNAL Cell 21 (3), 621-626 (1980)
PUBMED 6254663
REFERENCE 24 (bases 34422 to 36069; 39358 to 40986)
AUTHORS Slightom,J.L., Blechl,A.E. and Smithies,O.
TITLE Human fetal G gamma- and A gamma-globin genes: complete nucleotide
sequences suggest that DNA can be exchanged between these
duplicated genes
JOURNAL Cell 21 (3), 627-638 (1980)
PUBMED 7438203
REFERENCE 25 (bases 54618 to 56602)
AUTHORS Spritz,R.A., DeRiel,J.K., Forget,B.G. and Weissman,S.M.
TITLE Complete nucleotide sequence of the human delta-globin gene
JOURNAL Cell 21 (3), 639-646 (1980)
PUBMED 7438204
REFERENCE 26 (bases 62034 to 64083)
AUTHORS Lawn,R.M., Efstratiadis,A., O'Connell,C. and Maniatis,T.
TITLE The nucleotide sequence of the human beta-globin gene
JOURNAL Cell 21 (3), 647-651 (1980)
PUBMED 6254664
REFERENCE 27 (sites)
AUTHORS Efstratiadis,A., Posakony,J.W., Maniatis,T., Lawn,R.M.,
O'Connell,C., Spritz,R.A., DeRiel,J.K., Forget,B.G., Weissman,S.M.,
Slightom,J.L., Blechl,A.E., Smithies,O., Baralle,F.E.,
Shoulders,C.C. and Proudfoot,N.J.
TITLE The structure and evolution of the human beta-globin gene family
JOURNAL Cell 21 (3), 653-668 (1980)
PUBMED 6985477
REFERENCE 28 (bases 19864 to 19983)
AUTHORS Baralle,F.E., Shoulders,C.C., Goodbourn,S., Jeffreys,A. and
Proudfoot,N.J.
TITLE The 5' flanking region of human epsilon-globin gene
JOURNAL Nucleic Acids Res. 8 (19), 4393-4404 (1980)
PUBMED 6253916
REFERENCE 29 (bases 32353 to 43728)
AUTHORS Shen,S.H., Slightom,J.L. and Smithies,O.
TITLE A history of the human fetal globin gene duplication
JOURNAL Cell 26 (2 PT 2), 191-203 (1981)
PUBMED 7332928
REFERENCE 30 (sites)
AUTHORS Busslinger,M., Moschonas,N. and Flavell,R.A.
TITLE Beta + thalassemia: aberrant splicing results from a single point
mutation in an intron
JOURNAL Cell 27 (2 PT 1), 289-298 (1981)
PUBMED 6895866
REFERENCE 31 (bases 32353 to 33218; 51978 to 52472)
AUTHORS Duncan,C.H., Jagadeeswaran,P., Wang,R.R. and Weissman,S.M.
TITLE Structural analysis of templates and RNA polymerase III transcripts
of Alu family sequences interspersed among the human beta-like
globin genes
JOURNAL Gene 13 (2), 185-196 (1981)
PUBMED 6165649
REFERENCE 32 (sites)
AUTHORS Orkin,S.H. and Goff,S.C.
TITLE Nonsense and frameshift mutations in beta 0-thalassemia detected in
cloned beta-globin genes
JOURNAL J. Biol. Chem. 256 (19), 9782-9784 (1981)
PUBMED 6985481
REFERENCE 33 (bases 62454 to 62613)
AUTHORS Orkin,S.H., Goff,S.C. and Nathan,D.G.
TITLE Heterogeneity of DNA deletion in gamma delta beta-thalassemia
JOURNAL J. Clin. Invest. 67 (3), 878-884 (1981)
PUBMED 6162860
REFERENCE 34 (sites)
AUTHORS Trecartin,R.F., Liebhaber,S.A., Chang,J.C., Lee,K.Y., Kan,Y.W.,
Furbetta,M., Angius,A. and Cao,A.
TITLE beta zero thalassemia in Sardinia is caused by a nonsense mutation
JOURNAL J. Clin. Invest. 68 (4), 1012-1017 (1981)
PUBMED 6457059
REFERENCE 35 (sites)
AUTHORS Westaway,D. and Williamson,R.
TITLE An intron nucleotide sequence variant in a cloned beta
+-thalassaemia globin gene
JOURNAL Nucleic Acids Res. 9 (8), 1777-1788 (1981)
PUBMED 6264391
REFERENCE 36 (sites)
AUTHORS Moschonas,N., de Boer,E., Grosveld,F.G., Dahl,H.H., Wright,S.,
Shewmaker,C.K. and Flavell,R.A.
TITLE Structure and expression of a cloned beta o thalassaemic globin
gene
JOURNAL Nucleic Acids Res. 9 (17), 4391-4401 (1981)
PUBMED 6272205
REFERENCE 37 (bases 60489 to 60948)
AUTHORS Spritz,R.A.
TITLE Duplication/deletion polymorphism 5' - to the human beta globin
gene
JOURNAL Nucleic Acids Res. 9 (19), 5037-5047 (1981)
PUBMED 7312624
REFERENCE 38 (bases 59345 to 59593)
AUTHORS Miesfeld,R., Krystal,M. and Arnheim,N.
TITLE A member of a new repeated sequence family which is conserved
throughout eucaryotic evolution is found between the human delta
and beta globin genes
JOURNAL Nucleic Acids Res. 9 (22), 5931-5947 (1981)
PUBMED 6273813
REFERENCE 39 (bases 16595 to 17840)
AUTHORS Di Segni,G., Carrara,G., Tocchini-Valentini,G.R., Shoulders,C.C.
and Baralle,F.E.
TITLE Selective in vitro transcription of one of the two Alu family
repeats present in the 5' flanking region of the human
epsilon-globin gene
JOURNAL Nucleic Acids Res. 9 (24), 6709-6722 (1981)
PUBMED 7335492
REFERENCE 40 (sites)
AUTHORS Adams,J.G. 3rd, Steinberg,M.H., Newman,M.V., Morrison,W.T.,
Benz,E.J. Jr. and Iyer,R.
TITLE beta-Thalassemia present in cis to a new beta-chain structural
variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0]
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 78 (1), 469-473 (1981)
PUBMED 6165992
REFERENCE 41 (bases 61921 to 63824)
AUTHORS Spritz,R.A., Jagadeeswaran,P., Choudary,P.V., Biro,P.A.,
Elder,J.T., deRiel,J.K., Manley,J.L., Gefter,M.L., Forget,B.G. and
Weissman,S.M.
TITLE Base substitution in an intervening sequence of a beta+-thalassemic
human globin gene
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 78 (4), 2455-2459 (1981)
PUBMED 6264477
REFERENCE 42 (sites)
AUTHORS Baird,M., Driscoll,C., Schreiner,H., Sciarratta,G.V., Sansone,G.,
Niazi,G., Ramirez,F. and Bank,A.
TITLE A nucleotide change at a splice junction in the human beta-globin
gene is associated with beta 0-thalassemia
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 78 (7), 4218-4221 (1981)
PUBMED 6270663
REFERENCE 43 (sites)
AUTHORS Grosveld,F., Busslinger,M., Grosveld,G., Groffen,J., DeKleine,A.
and Flavell,R.A.
TITLE The structure and expression of the haemoglobin genes
JOURNAL Adv. Exp. Med. Biol. 158, 65-80 (1982)
PUBMED 6297279
REFERENCE 44 (sites)
AUTHORS Treisman,R., Proudfoot,N.J., Shander,M. and Maniatis,T.
TITLE A single-base change at a splice site in a beta 0-thalassemic gene
causes abnormal RNA splicing
JOURNAL Cell 29 (3), 903-911 (1982)
PUBMED 7151176
REFERENCE 45 (bases 63823 to 64083)
AUTHORS Poncz,M., Ballantine,M., Solowiejczyk,D., Barak,I., Schwartz,E. and
Surrey,S.
TITLE beta-Thalassemia in a Kurdish Jew. Single base changes in the
T-A-T-A box
JOURNAL J. Biol. Chem. 257 (11), 5994-5996 (1982)
PUBMED 7076659
REFERENCE 46 (bases 61873 to 62198; 62375 to 62448)
AUTHORS Gorski,J., Fiori,M. and Mach,B.
TITLE A new nonsense mutation as the molecular basis for beta
thalassaemia
JOURNAL J. Mol. Biol. 154 (3), 537-540 (1982)
PUBMED 6896219
REFERENCE 47 (bases 50716 to 51215)
AUTHORS Jagadeeswaran,P., Tuan,D., Forget,B.G. and Weissman,S.M.
TITLE A gene deletion ending at the midpoint of a repetitive DNA sequence
in one form of hereditary persistence of fetal haemoglobin
JOURNAL Nature 296 (5856), 469-470 (1982)
PUBMED 6174873
REFERENCE 48 (sites)
AUTHORS Orkin,S.H., Kazazian,H.H. Jr., Antonarakis,S.E., Goff,S.C.,
Boehm,C.D., Sexton,J.P., Waber,P.G. and Giardina,P.J.
TITLE Linkage of beta-thalassaemia mutations and beta-globin gene
polymorphisms with DNA polymorphisms in human beta-globin gene
cluster
JOURNAL Nature 296 (5858), 627-631 (1982)
PUBMED 6280057
REFERENCE 49 (sites)
AUTHORS Ottolenghi,S. and Giglioni,B.
TITLE The deletion in a type of delta 0-beta 0-thalassaemia begins in an
inverted AluI repeat
JOURNAL Nature 300 (5894), 770-771 (1982)
PUBMED 6184621
REFERENCE 50 (bases 62651 to 62715)
AUTHORS Spence,S.E., Pergolizzi,R.G., Donovan-Peluso,M., Kosche,K.A.,
Dobkin,C.S. and Bank,A.
TITLE Five nucleotide changes in the large intervening sequence of a beta
globin gene in a beta+ thalassemia patient
JOURNAL Nucleic Acids Res. 10 (4), 1283-1294 (1982)
PUBMED 6280138
REFERENCE 51 (bases 60676 to 62137)
AUTHORS Moschonas,N., de Boer,E. and Flavell,R.A.
TITLE The DNA sequence of the 5' flanking region of the human beta-globin
gene: evolutionary conservation and polymorphic differences
JOURNAL Nucleic Acids Res. 10 (6), 2109-2120 (1982)
PUBMED 6985483
REFERENCE 52 (sites)
AUTHORS Alan,M., Grindlay,G.J., Stefani,L. and Paul,J.
TITLE Epsilon globin gene transcripts originating upstream of the mRNA
cap site in K562 cells and normal human embryos
JOURNAL Nucleic Acids Res. 10 (17), 5133-5147 (1982)
PUBMED 6292831
REFERENCE 53 (sites)
AUTHORS Kinniburgh,A.J., Maquat,L.E., Schedl,T., Rachmilewitz,E. and
Ross,J.
TITLE mRNA-deficient beta o-thalassemia results from a single nucleotide
deletion
JOURNAL Nucleic Acids Res. 10 (18), 5421-5427 (1982)
PUBMED 6292840
REFERENCE 54 (bases 54438 to 54740)
AUTHORS Kimura,A., Matsunaga,E., Ohta,Y., Fujiyoshi,T., Matsuo,T.,
Nakamura,T., Imamura,T., Yanase,T. and Takagi,Y.
TITLE Structure of cloned delta-globin genes from a normal subject and a
patient with delta-thalassemia; sequence polymorphisms found in the
delta-globin gene region of Japanese individuals
JOURNAL Nucleic Acids Res. 10 (19), 5725-5732 (1982)
PUBMED 6292847
REFERENCE 55 (bases 10410 to 13774)
AUTHORS Shen,S.H. and Smithies,O.
TITLE Human globin psi B2 is not a globin-related sequence
JOURNAL Nucleic Acids Res. 10 (23), 7809-7818 (1982)
PUBMED 6897566
REFERENCE 56 (sites)
AUTHORS Spritz,R.A. and Orkin,S.H.
TITLE Duplication followed by deletion accounts for the structure of an
Indian deletion beta (0)-thalassemia gene
JOURNAL Nucleic Acids Res. 10 (24), 8025-8029 (1982)
PUBMED 7162987
REFERENCE 57 (bases 62373 to 62421)
AUTHORS Flavell,R.A., Bud,H., Bullman,H., Busslinger,M., de Boer,E., de
Kleine,A., Golden,L., Groffen,J., Grosveld,F.G., Mellor,A.L.,
Moschonas,N. and Weiss,E.
TITLE The structure and expression of mammalian gene clusters
MEDLINE 83144268
JOURNAL Prog. Clin. Biol. Res. 103, 37-55 (1982)
REFERENCE 58 (sites)
AUTHORS Ley,T.J. and Nienhuis,A.W.
TITLE A weak upstream promoter gives rise to long human beta-globin RNA
molecules
JOURNAL Biochem. Biophys. Res. Commun. 112 (3), 1041-1048 (1983)
PUBMED 6303333
REFERENCE 59 (sites)
AUTHORS Carlson,D.P. and Ross,J.
TITLE Human beta-globin promoter and coding sequences transcribed by RNA
polymerase III
JOURNAL Cell 34 (3), 857-864 (1983)
PUBMED 6194893
REFERENCE 60 (sites)
AUTHORS Allan,M., Lanyon,W.G. and Paul,J.
TITLE Multiple origins of transcription in the 4.5 Kb upstream of the
epsilon-globin gene
JOURNAL Cell 35 (1), 187-197 (1983)
PUBMED 6194897
REFERENCE 61 (sites)
AUTHORS Vanin,E.F., Henthorn,P.S., Kioussis,D., Grosveld,F. and Smithies,O.
TITLE Unexpected relationships between four large deletions in the human
beta-globin gene cluster
JOURNAL Cell 35 (3 PT 2), 701-709 (1983)
PUBMED 6652684
REFERENCE 62 (bases 50744 to 67204)
AUTHORS Poncz,M., Schwartz,E., Ballantine,M. and Surrey,S.
TITLE Nucleotide sequence analysis of the delta beta-globin gene region
in humans
JOURNAL J. Biol. Chem. 258 (19), 11599-11609 (1983)
PUBMED 6311816
REFERENCE 63 (bases 62050 to 62050; 62279 to 62279; 62283 to 62283)
AUTHORS Treisman,R., Orkin,S.H. and Maniatis,T.
TITLE Specific transcription and RNA splicing defects in five cloned
beta-thalassaemia genes
JOURNAL Nature 302 (5909), 591-596 (1983)
PUBMED 6188062
REFERENCE 64 (bases 62190 to 62244)
AUTHORS Chang,J.C., Alberti,A. and Kan,Y.W.
TITLE A beta-thalassemia lesion abolishes the same Mst II site as the
sickle mutation
JOURNAL Nucleic Acids Res. 11 (22), 7789-7794 (1983)
PUBMED 6316272
REFERENCE 65 (bases 50716 to 53976)
AUTHORS Maeda,N., Bliska,J.B. and Smithies,O.
TITLE Recombination and balanced chromosome polymorphism suggested by DNA
sequences 5' to the human delta-globin gene
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 80 (16), 5012-5016 (1983)
PUBMED 6308666
REFERENCE 66 (sites)
AUTHORS Kimura,A., Ohta,Y., Fukumaki,Y. and Takagi,Y.
TITLE A fusion gene in man: DNA sequence analysis of the abnormal globin
gene of hemoglobin Miyada
JOURNAL Biochem. Biophys. Res. Commun. 119 (3), 968-974 (1984)
PUBMED 6324786
REFERENCE 67 (sites)
AUTHORS Kazazian,H.H. Jr., Orkin,S.H., Antonarakis,S.E., Sexton,J.P.,
Boehm,C.D., Goff,S.C. and Waber,P.G.
TITLE Molecular characterization of seven beta-thalassemia mutations in
Asian Indians
JOURNAL EMBO J. 3 (3), 593-596 (1984)
PUBMED 6714226
REFERENCE 68 (sites)
AUTHORS Guida,S., Giglioni,B., Comi,P., Ottolenghi,S., Camaschella,C. and
Saglio,G.
TITLE The beta-globin gene in Sardinian delta beta 0-thalassemia carries
a C----T nonsense mutation at codon 39
JOURNAL EMBO J. 3 (4), 785-787 (1984)
PUBMED 6327288
REFERENCE 69 (sites)
AUTHORS Giglioni,B., Casini,C., Mantovani,R., Merli,S., Comi,P.,
Ottolenghi,S., Saglio,G., Camaschella,C. and Mazza,U.
TITLE A molecular study of a family with Greek hereditary persistence of
fetal hemoglobin and beta-thalassemia
JOURNAL EMBO J. 3 (11), 2641-2645 (1984)
PUBMED 6210198
REFERENCE 70 (bases 61557 to 61623)
AUTHORS Semenza,G.L., Malladi,P., Surrey,S., Delgrosso,K., Poncz,M. and
Schwartz,E.
TITLE Detection of a novel DNA polymorphism in the beta-globin gene
cluster
JOURNAL J. Biol. Chem. 259 (10), 6045-6048 (1984)
PUBMED 6327661
REFERENCE 71 (sites)
AUTHORS Orkin,S.H., Antonarakis,S.E. and Kazazian,H.H. Jr.
TITLE Base substitution at position -88 in a beta-thalassemic globin
gene. Further evidence for the role of distal promoter element
ACACCC
JOURNAL J. Biol. Chem. 259 (14), 8679-8681 (1984)
PUBMED 6086605
REFERENCE 72 (bases 45336 to 47463)
AUTHORS Chang,L.Y. and Slightom,J.L.
TITLE Isolation and nucleotide sequence analysis of the beta-type globin
pseudogene from human, gorilla and chimpanzee
JOURNAL J. Mol. Biol. 180 (4), 767-784 (1984)
PUBMED 6098690
REFERENCE 73 (sites)
AUTHORS Grindlay,G.J., Lanyon,W.G., Allan,M. and Paul,J.
TITLE Alternative sites of transcription initiation upstream of the
canonical cap site in human gamma-globin and beta-globin genes
JOURNAL Nucleic Acids Res. 12 (4), 1811-1820 (1984)
PUBMED 6701091
REFERENCE 74 (sites)
AUTHORS Stoeckert,C.J. Jr., Collins,F.S. and Weissman,S.M.
TITLE Human fetal globin DNA sequences suggest novel conversion event
JOURNAL Nucleic Acids Res. 12 (11), 4469-4479 (1984)
PUBMED 6330670
REFERENCE 75 (sites)
AUTHORS Mager,D.L. and Henthorn,P.S.
TITLE Identification of a retrovirus-like repetitive element in human DNA
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 81 (23), 7510-7514 (1984)
PUBMED 6095301
REFERENCE 76 (bases 19120 to 61776)
AUTHORS Collins,F.S. and Weissman,S.M.
TITLE The molecular genetics of human hemoglobin
JOURNAL Prog. Nucleic Acid Res. Mol. Biol. 31, 315-462 (1984)
PUBMED 6397774
REFERENCE 77 (bases 34276 to 34276; 34282 to 34282; 34321 to 34321)
AUTHORS Gilman,J.G. and Huisman,T.H.
TITLE DNA sequence variation associated with elevated fetal G gamma
globin production
JOURNAL Blood 66 (4), 783-787 (1985)
PUBMED 2412616
REFERENCE 78 (sites)
AUTHORS Ruskin,B., Greene,J.M. and Green,M.R.
TITLE Cryptic branch point activation allows accurate in vitro splicing
of human beta-globin intron mutants
JOURNAL Cell 41 (3), 833-844 (1985)
PUBMED 3879973
REFERENCE 79 (sites)
AUTHORS Lang,K.M. and Spritz,R.A.
TITLE Cloning specific complete polyadenylylated 3'-terminal cDNA
segments
JOURNAL Gene 33 (2), 191-196 (1985)
PUBMED 2581851
REFERENCE 80 (bases 1 to 16593)
AUTHORS Li,Q., Powers,P.A. and Smithies,O.
TITLE Nucleotide sequence of 16-kilobase pairs of DNA 5' to the human
epsilon-globin gene
JOURNAL J. Biol. Chem. 260 (28), 14901-14910 (1985)
PUBMED 4066658
REFERENCE 81 (sites)
AUTHORS Gelinas,R., Endlich,B., Pfeiffer,C., Yagi,M. and
Stamatoyannopoulos,G.
TITLE G to A substitution in the distal CCAAT box of the A gamma-globin
gene in Greek hereditary persistence of fetal haemoglobin
JOURNAL Nature 313 (6000), 323-325 (1985)
PUBMED 2578619
REFERENCE 82 (sites)
AUTHORS Collins,F.S., Metherall,J.E., Yamakawa,M., Pan,J., Weissman,S.M.
and Forget,B.G.
TITLE A point mutation in the A gamma-globin gene promoter in Greek
hereditary persistence of fetal haemoglobin
JOURNAL Nature 313 (6000), 325-326 (1985)
PUBMED 2578620
REFERENCE 83 (bases 67071 to 73308)
AUTHORS Hattori,M., Hidaka,S. and Sakaki,Y.
TITLE Sequence analysis of a KpnI family member near the 3' end of human
beta-globin gene
JOURNAL Nucleic Acids Res. 13 (21), 7813-7827 (1985)
PUBMED 2999705
REFERENCE 84 (sites)
AUTHORS van Santen,V.L. and Spritz,R.A.
TITLE mRNA precursor splicing in vivo: sequence requirements determined
by deletion analysis of an intervening sequence
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 82 (9), 2885-2889 (1985)
PUBMED 3857622
REFERENCE 85 (sites)
AUTHORS Tuan,D., Solomon,W., Li,Q. and London,I.M.
TITLE The 'beta-like-globin' gene domain in human erythroid cells
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 82 (19), 6384-6388 (1985)
PUBMED 3879975
REFERENCE 86 (sites)
AUTHORS Chabot,B., Black,D.L., LeMaster,D.M. and Steitz,J.A.
TITLE The 3' splice site of pre-messenger RNA is recognized by a small
nuclear ribonucleoprotein
JOURNAL Science 230 (4732), 1344-1349 (1985)
PUBMED 2933810
REFERENCE 87 (bases 21354 to 21360)
AUTHORS Collins,F.S.
JOURNAL Unpublished
REFERENCE 88 (bases 58799 to 58958; 63036 to 63295)
AUTHORS Popovich,B.W., Rosenblatt,D.S., Kendall,A.G. and Nishioka,Y.
TITLE Molecular characterization of an atypical beta-thalassemia caused
by a large deletion in the 5' beta-globin gene region
JOURNAL Am. J. Hum. Genet. 39 (6), 797-810 (1986)
PUBMED 3799598
REFERENCE 89 (bases 54874 to 54892)
AUTHORS Lapoumeroulie,C., Pagnier,J., Bank,A., Labie,D. and
Krishnamoorthy,R.
TITLE Beta thalassemia due to a novel mutation in IVS 1 sequence donor
site consensus sequence creating a restriction site
JOURNAL Biochem. Biophys. Res. Commun. 139 (2), 709-713 (1986)
PUBMED 3021139
REFERENCE 90 (bases 62373 to 62419)
AUTHORS Metherall,J.E., Collins,F.S., Pan,J., Weissman,S.M. and Forget,B.G.
TITLE Beta zero thalassemia caused by a base substitution that creates an
alternative splice acceptor site in an intron
JOURNAL EMBO J. 5 (10), 2551-2557 (1986)
PUBMED 3780671
REFERENCE 91 (bases 37640 to 37677; 40162 to 40199)
AUTHORS Tate,V.E., Hill,A.V., Bowden,D.K., Sadler,J.R., Weatherall,D.J. and
Clegg,J.B.
TITLE A silent deletion in the beta-globin gene cluster
JOURNAL Nucleic Acids Res. 14 (12), 4743-4750 (1986)
PUBMED 2425337
REFERENCE 92 (sites)
AUTHORS Prchal,J.T., Cashman,D.P. and Kan,Y.W.
TITLE Hemoglobin Long Island is caused by a single mutation (adenine to
cytosine) resulting in a failure to cleave amino-terminal
methionine
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 83 (1), 24-27 (1986)
PUBMED 3455755
REFERENCE 93 (bases 59589 to 59718; 72211 to 72340)
AUTHORS Gilman,J.G. and Abraham,J.
TITLE DNA sequence analysis of the Dutch beta-0-thalassemia deletion
JOURNAL Biomed. Biochim. Acta 46, 131-135 (1987)
REFERENCE 94 (bases 43723 to 50721)
AUTHORS Miyamoto,M.M., Slightom,J.L. and Goodman,M.
TITLE Phylogenetic relations of humans and African apes from DNA
sequences in the psi eta-globin region
JOURNAL Science 238 (4825), 369-373 (1987)
PUBMED 3116671
REFERENCE 95 (sites)
AUTHORS Fei,Y.J., Stoming,T.A., Efremov,G.D., Efremov,D.G., Battacharia,R.,
Gonzalez-Redondo,J.M., Altay,C., Gurgey,A. and Huisman,T.H.
TITLE Beta-thalassemia due to a T----A mutation within the ATA box
JOURNAL Biochem. Biophys. Res. Commun. 153 (2), 741-747 (1988)
PUBMED 3382401
REFERENCE 96 (bases 55038 to 55052)
AUTHORS Atweh,G.F., Brickner,H.E., Zhu,X.X., Kazazian,H.H. Jr. and
Forget,B.G.
TITLE New amber mutation in a beta-thalassemic gene with nonmeasurable
levels of mutant messenger RNA in vivo
JOURNAL J. Clin. Invest. 82 (2), 557-561 (1988)
PUBMED 3403716
REFERENCE 97 (sites)
AUTHORS Engelke,D.R., Hoener,P.A. and Collins,F.S.
TITLE Direct sequencing of enzymatically amplified human genomic DNA
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 85 (2), 544-548 (1988)
PUBMED 3267215
REFERENCE 98 (sites)
AUTHORS Guidal,C., Lapoumeroulie,C., Krishnamoorthy,R. and Elion,J.
TITLE Sequence correction and reassignment of the TaqI polymorphic site
in the human inter-gamma-globin gene region, an African-specific
marker
JOURNAL Unpublished
REFERENCE 99 (bases 16594 to 19305)
AUTHORS Trepicchio,W.L., Dyer,M.A., Hardison,R.G. and Baron,M.H.
TITLE Upstream regulatory region of the human embryonic beta-like globin
gene, epsilon
JOURNAL Unpublished (1993)
REFERENCE 100 (bases 1 to 73308)
AUTHORS Teixeira,A., Tahiri-Alaoui,A., West,S., Thomas,B., Ramadass,A.,
Martianov,I., Dye,M., James,W., Proudfoot,N.J. and Akoulitchev,A.
TITLE Autocatalytic RNA cleavage in the human beta-globin pre-mRNA
promotes transcription termination
JOURNAL Nature 432 (7016), 526-530 (2004)
PUBMED 15565159
COMMENT On Feb 16, 1994 this sequence version replaced gi:183807.
[1] cRNA fragments.
[2] mRNA.
[5] sites; polyadenylation signal and site for the beta gene.
[4] cDNA from normal and thalassemic mRNAs.
[6] cDNA.
[9] mRNA and cDNA fragments.
[10] mRNA.
[7] cDNA.
[13] see comment below for 35854 to 35946 - may be 40770 to 40862.
[19] sites; amber mutation at codon 17 of the beta chain.
[22] sites; gene order for the beta-like globin cluster.
[27] sites; consensus sequences in the promoter regions.
[40] sites; mutation associated with Hb Vicksburg.
[41] beta thalassemia DNA.
[42] sites; mutation associated with beta-0 thalassemia.
[35] sites; mutation associated with beta-plus thalassemia.
[36] sites; mutation associated with beta-0 thalassemia.
[37] six alleles over this span.
[32] sites; mutations associated with beta-0 thalassemia.
[34] sites; mutation associated with beta-0 thalassemia.
[52] sites; alternative cap sites for mRNA.
[53] sites; mutation associated with beta-plus thalassemia.
[56] sites; deletion mutation associated with beta-0 thalassemia.
[48] sites; mutations associated with beta thalassemias.
[49] sites; deletion mutation; for sequence, see separate entry.
[62] DNA from Kurdish Jew with thalassemia.
[58] sites; promoter region for beta gene.
[59] sites; termini for RNA polymerase III transcripts.
[60] sites; alternative cap sites for mRNA.
[61] sites; deletion mutations associated with thalassemias;.
[65] for the R allele;.
[73] sites; beta and gamma gene cap sites.
[71] sites; mutation associated with beta thalassemia.
[66] sites; Miyada Hb lesion; for sequence, see separate entry.
[75] sites; hsRTVL-H element; for sequence, see separate entry.
[67] sites; mutations associated with thalassemia.
[68] sites; mutation associated with thalassemia.
[69] sites; mutation associated with thalassemia.
[76] see comment; review.
[74] sites; mutations in the A-gamma gene.
[81] sites; mutation in promoter region leading to HPFH;.
[82] sites; mutation in promoter region leading to HPFH.
[85] sites; DNAse I hypersensitivity sites in the region.
[78] sites; cryptic branch points in beta IVS1.
[79] sites; 3' segments of beta and G-gamma cDNAs.
[84] sites; mutational analysis of G-gamma IVS-2.
[86] sites; small nuclear ribonucleoprotein binding site to mRNA.
[92] sites; hemoglobin Long Island mutation.
[94] revises [72].
[95] sites; mutations resulting in beta-thalassemia.
[97] sites; sickle cell anemia mutation site.
[30] sites; thalassemia mutations.
[43] sites; thalassemia mutations.
[44] sites; thalassemia mutation.
[21] sites; thalassemia mutation.
[90] beta-0 thalassemia mutations.
This 73 kb sequence, which includes all of the known beta genes in
the cluster on chromosome 11, was compiled from the following
sources primarily:
bases references
------ ------------
1 to 10409 [80]
10410 to 13774 [55]
13775 to 16594 [80]
16595 to 19304 [99]
19305 to 21381 [23], [28], [39]
21382 to 32352 [63; see acknowledgments therein; bases
31888-32020 sequenced on one strand only]
32353 to 43728 [29]
43729 to 50715 [94]
50716 to 67204 [47], [62]
67205 to 73308 [83]
Other sequence work is referenced and annotated below. Oliver
Smithies provided the sequence in [80] via Arpanet and Francis
Collins supplied a diskette with the sequence in [76].
Computer-readable sequence for [94] kindly provided by
M.M.Miyamoto, 15-FEB-1988.
The five beta-like globin genes are found within a 45 kb cluster on
chromosome 11 in the following order:
5'-epsilon -G-gamma -A-gamma -delta -beta-3' [22]
Additionally, the pseudogene beta-1 is located between the A-gamma
and delta genes [72]. A region 5' to the epsilon gene was thought
to be another pseudogene; however [55] shows this not to be so.
These embryonic, fetal and adult beta-like genes have the same
overall exonic structure, leading to the conclusion that they are
derived from one ancestral gene. In particular, they have many
consensus sequences and repetitive sequences in common which have
been analyzed by [27] and [76].
Epsilon gene
------------
The epsilon globin gene (hbe below) is normally expressed in the
embryonic yolk sac: two epsilon chains together with two zeta
chains (an alpha-like globin; see separate entry) constitute the
embryonic hemoglobin Hb Gower I; two epsilon chains together with
two alpha chains form the embryonic Hb Gower II. Both of these
embryonic hemoglobins are normally supplanted by fetal, and later,
adult hemoglobin.
The promoter region sequences 'ccaat', 'ata' and 'cttccg' found at
19403, 19458 and 19495 are characteristic of all human beta-like
genes, as well as of some other mammalian genes, and are thought to
influence initiation of transcription and translation [27],[76].
However, at least nine alternative cap sites which do not possess
these conserved sequences have been found upstream from the
so-called canonical cap sites at 19486 and 19488 [52],[60].
The Alu family sequences found at 16892-17158 and 17927-18190 are
typical of the 5' flanking regions of the beta-like globin genes
[23],[39]. The first of these bipolar repeats has been shown to be
active as a template for RNA polymerase III [39].
G-gamma and A-gamma genes
-------------------------
The gamma globin genes (hbgg and hbga below) are normally expressed
in the fetal liver, spleen and bone marrow. Two gamma chains
together with two alpha chains constitute fetal hemoglobin (HbF)
which is normally replaced by adult hemoglobin (HbA) at birth. In
some beta-thalassemias and related conditions (HPFH or 'hereditary
persistence of fetal hemoglobin'), gamma chain production continues
into adulthood. The mapping of deletions in these pathologies is
therefore of special interest with regard to developmental control
mechanisms.
The two types of gamma chains differ at residue 136 where glycine
is found in the G-gamma product and alanine is found in the A-gamma
product. The former is predominant at birth. Because of the
sequence identity of the two genes over large stretches, it was not
always possible in the early work to know which sequence was being
investigated [13],[15],[17]. Moreover, because allelic variation
has been reported for each of these non-allelic genes, further
sequence work is required to determine the consensus sequence for
each. Thus far the sequences of two A-gamma alleles have been
reported ([24]; see separate entry which annotates the allelic
variation). The second introns for the hbgg and hbga genes shown
below contain 886 and 866 bases respectively, while their alleles
on the opposing chromosome have 904 and 876 bases for the
corresponding introns. [24] and [29] present an analysis of this
phenomenon and conclude that intergenic exchange can occur in human
germ line cells with significant frequency.
Given the above-mentioned uncertainties with regard to polymorphism
and material, differences, where annotated, are treated as
variations rather than as conflicts.
The promoter region sequences 'ccaat', 'ata' and 'cttctg' found at
bases 34390, 34448 and 34485 in the hbgg gene, and bases 39326,
39384 and 39421 in the hbga gene, are characteristic of all
beta-like genes, as well as of some other mammalian genes, and are
thought to influence transcription and translation [27],[76]. The
gamma genes each manifest duplicate 'ccaat' boxes at positions
34363 (hbgg) and 39299 (hbga). Alternative cap sites are active in
vitro upstream from the canonical cap sites at 34478 and 39414: at
bases 34398, 34408, 34418 and 34428 for hbgg, and at bases 39334,
39344, 39354 and 39364 for hbga [73]. Alternative cap sites have
also been reported for epsilon and beta mRNAs when there is no
duplication of the 'ccaat' sequence. [81] and [82] show that the
distal 'ccaat' box for the hbga gene (for the B allele -- see
separate sequence) has some vital function: a g -> a mutation at
base 39297 is apparently responsible for one form of Greek HPFH.
The Alu family sequences found at bases 32390-32723 (approx.) and
37325-37562 (approx.) are typical of the beta-like globin Alu's
[27],[76],[31],[29]. A study of the hbgg repeat has revealed RNA
transcription by polymerase III [31]( also reported for Alu regions
in the 5' flanks of the epsilon and beta genes).
Pseudo-beta-1
-------------
Human, gorilla and chimpanzee beta-like pseudogenes were sequenced
and compared (see separate entries for the other primate sequences)
by [72] and revised by [94]. The pseudogene structure was deduced
through comparison with the A-gamma globin gene. Base substitutions
in the initiation codon and in codons downstream, that create
internal termination signals in exons 2 and 3, make this sequence a
pseudogene.
Delta and beta genes
--------------------
The delta and beta genes (denoted hbd and hbb below) are normally
expressed in the adult: two alpha chains plus two beta chains
constitute HbA, which in normal adult life comprises about 97% of
the total hemoglobin. Two alpha chains plus two delta chains
constitute HbA-2, which with HbF comprises the remaining 3% of
adult hemoglobin.
The sequence given below has been reconstructed from the sequences
reported by [47] and [62]: the mutation at base 62143 is apparently
sufficient to distinguish the Kurdish Jew thalassemic sequence from
a normal (consensus) beta globin DNA; [62] has resolved all
sequence differences to date with exception of the differences
reported herein as variations.
The promoter region sequences 'ccaat', 'ata' and 'cttctg' found at
bases 54672, 54709 and 54747 in the delta gene, and at bases 62061,
62106 and 62144 in the beta gene, are characteristic of all
beta-like genes, as well as of some other mammalian genes, and are
thought to influence transcription and translation [27],[76].
However, alternative cap sites have been found for these genes as
well as other beta-like genes [58],[73].
[95] describes the mutation (substitution of 'a' for 't' at
position 62107, thereby destroying the promoter) found in an Hb
Lepore-beta+ -thalassemia patient, who was homozygous for this
mutation. The father who had the simple beta-thalassemia trait was
found to be heterozygous.
A form of thalassemia exists, where 19 bp are added after the first
exon, starting at position 62390 and ending at a stop codon at
position 62406-62408 [30],[43],[57]. This aberrant splicing is
caused by a mutation of 'g' to 'a' in the first intron of
beta-hemoglobin at position 62388. The substitution of a 'g' for a
't' at position 62394 also causes premature splicing and results in
an abnormal and abbreviated beta hemoglobin [90].
Another form of beta-thalassemia is produced by the substitution of
an 'a' for a 'g' at position 62632. This causes a readthrough at
the exon/intron boundary of exon 2/intron 2 [44].
The Alu family sequences found at bases 50915, 51976, 65513 and
66776 are again typical of the beta-like globin Alu's. These
sequences are of considerable interest in relation to regulation,
recombination and transcription by RNA polymerase III.
There are non-Alu repetitive elements in the gene cluster that have
been partially characterized: the EC-1 repeat [38] and a
retrovirus-like element in the 3' flank about 300 kb downstream of
this sequence [75] (see separate entry); there are numerous repeats
in the 5' flank which will be included in a future update [80].
Reference [83] has characterized a novel KpnI family sequence in
the 3' flank of the cluster.
Potential polyadenylation signals were identified for the following
genes:
hbe positions 21055-21060
hbgg positions 36043-36048
hbga positions 40959-40964
hbd positions 56365-56370
hbb positions 63718-63723.
FEATURES Qualifiers
source /organism="Homo sapiens"
/mol_type="genomic DNA"
/db_xref="taxon:9606"
/map="11p15.5"
protein /gene="HBG1"
intron_pos 31:2 (1/2)
intron_pos 106:0 (2/2)
BEGIN
1 MGHFTEEDKA TITSLWGKVN VEDAGGETLG RLLVVYPWTQ RFFDSFGNLS SASAIMGNPK
61 VKAHGKKVLT SLGDAIKHLD DLKGTFAQLS ELHCDKLHVD PENFKLLGNV LVTVLAIHFG
121 KEFTPEVQAS WQKMVTAVAS ALSSRYH
//