Intergenic DNA sequences flanking the pseudo alpha globin genes of human and chimpanzee

DNA sequences homologous to adult alpha-globin genes are dispersed in the mouse. Two functional genes are tightly linked on chromosome 11. Pseudogenes have been assigned to chromosomes 15 and 17 by analysis of interspecies somatic cell hybrids. We have now further characterized the second of these pseudogenes, Hba-a4. The gene is highly polymorphic, with three forms occurring in a panel of 15 inbred strains and a fourth occurring in an inbred strain derived from M. m. molossinus. Analysis of Hba-a4 alleles in CXB, BXH, and AKXL recombinant inbred strains placed Hba-a4 6.60 +/- 3.14 cM centromeric to H-2. Analysis of congenic mouse strains confirmed the linkage and the gene order. Hba-a4 is the first mammalian dispersed pseudogene to be localized in a linkage map, and should provide a useful marker for the region of chromosome 17 proximal to H-2.

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Repetitive DNA sequences near three humanβ-type globin genes

Nucleic Acids Research ◽

10.1093/nar/8.15.3319 ◽

1980 ◽

Vol 8 (15) ◽

pp. 3319-3333 ◽

Cited By ~ 24

Author(s):

Lesley W. Coggins ◽

G.Joan Grindlay ◽

J.Keith Vass ◽

Alison A. Slater ◽

Paul Montague ◽

...

Keyword(s):

Repetitive Dna ◽

Dna Sequences ◽

Repetitive Dna Sequences ◽

Globin Genes

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The coordinate replication of the human beta-globin gene domain reflects its transcriptional activity and nuclease hypersensitivity

Molecular and Cellular Biology ◽

10.1128/mcb.8.11.4958-4965.1988 ◽

1988 ◽

Vol 8 (11) ◽

pp. 4958-4965

Author(s):

V Dhar ◽

D Mager ◽

A Iqbal ◽

C L Schildkraut

Keyword(s):

Cell Lines ◽

Dna Sequences ◽

Globin Gene ◽

K562 Cells ◽

Globin Genes ◽

Beta Globin ◽

Beta Globin Gene ◽

Hypersensitive Sites ◽

Flanking Sequences ◽

Globin Gene Domain

The temporal order of replication of DNA sequences in the chromosomal domain containing the human beta-globin gene cluster and its flanking sequences (140 kilobases) was measured and compared in two different human cell lines. In human erythroleukemia (K562) cells, in which embryonic and fetal globin genes are transcribed, all of the sequences we examined from the beta-globin domain replicated early during S phase, while in HeLa cells, in which globin genes are transcriptionally silent, these sequences replicated late during S. Potential sites of initiation of DNA replication within this domain were identified. The beta-globin gene domain was also found to differ with respect to the nuclease sensitivity of the chromatin in these two cell lines. In K562 cells, hypersensitive sites for endogenous nucleases and DNase I were present in the chromatin near the earliest-replicating segments in the beta-globin domain.

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Screening for mutations in human alpha-globin genes by nonradioactive single-strand conformation polymorphism

Brazilian Journal of Medical and Biological Research ◽

10.1590/s0100-879x2003001100004 ◽

2003 ◽

Vol 36 (11) ◽

pp. 1471-1474 ◽

Cited By ~ 6

Author(s):

S.B. Jorge ◽

M.B. Melo ◽

F.F. Costa ◽

M.F. Sonati

Keyword(s):

Single Strand Conformation Polymorphism ◽

Single Strand ◽

Globin Genes ◽

Alpha Globin ◽

Conformation Polymorphism

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Beta zero-thalassemia in association with a gamma-globin gene quadruplication

Blood ◽

10.1182/blood.v68.6.1394.bloodjournal6861394 ◽

1986 ◽

Vol 68 (6) ◽

pp. 1394-1397

Author(s):

KG Yang ◽

JZ Liu ◽

F Kutlar ◽

A Kutlar ◽

C Altay ◽

...

Keyword(s):

Clinical Condition ◽

Globin Gene ◽

Normal Chromosome ◽

Gene Arrangement ◽

Beta Thalassemia ◽

Globin Genes ◽

Thalassemia Intermedia ◽

Gamma Globin ◽

Alpha Globin

We have studied the hematology, hemoglobin composition, and globin gene arrangements in one young Turkish boy with a beta zero-thalassemia homozygosity and in 11 of his relatives. Evidence is presented that the chromosome with the beta zero-thalassemia determinant carries a gamma- globin gene quadruplication, perhaps in a -G gamma-G gamma-G gamma-A gamma-gene arrangement. The eight gamma-globin genes in this patient produced G gamma and A gamma chains in a 95 to 5 ratio, and nearly 99% of the patient's hemoglobin was of the fetal type. The clinical condition resembled that of a thalassemia intermedia. HbF levels in eight beta-thalassemia heterozygotes varied between 0.5 and 4.2% and the percentages of G gamma in this HbF averaged at 87% or 95%; this level is to some extent related to the haplotype of the normal chromosome. All subjects carried four alpha-globin genes; a new BglII polymorphism was observed within the psi alpha-globin gene.

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Alpha globin variation in the long-tailed macaque suggests malaria selection

10.1101/2020.10.21.344853 ◽

2020 ◽

Author(s):

C.L. Faust ◽

F. Rangkuti ◽

S. G. Preston ◽

A. Boyd ◽

P. Flammer ◽

...

Keyword(s):

Copy Number ◽

Macaca Fascicularis ◽

Missense Mutations ◽

Globin Genes ◽

Globin Chain ◽

Computational Simulations ◽

Human Haemoglobin ◽

Alpha Globin ◽

Number Variation ◽

Almost All

AbstractHuman haemoglobin variants, such as sickle, confer protection against death from malaria; consequently, frequencies of such variants are often greatly elevated in humans from malaria endemic regions. Among non-human primates, the long-tailed macaque, Macaca fascicularis, also displays substantial haemoglobin variation. Almost all M. fascicularis haemoglobin variation is in the alpha globin chain, encoded by two linked genes: HBA1 and HBA2. We demonstrate that alpha globin variation in M. fascicularis correlates with the strength of malaria selection. We identify a range of missense mutations in M. fascicularis alpha globin and demonstrate that some of these exhibit a striking HBA1 or HBA2 specificity, a pattern consistent with computational simulations of selection on genes exhibiting copy number variation. We propose that M. fascicularis accumulated amino acid substitutions in its alpha globin genes under malaria selection, in a process that closely mirrors, but does not entirely converge with, human malaria adaptation.

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Inactivation of mouse alpha-globin gene by homologous recombination: mouse model of hemoglobin H disease

Blood ◽

10.1182/blood.v88.5.1846.bloodjournal8851846 ◽

1996 ◽

Vol 88 (5) ◽

pp. 1846-1851 ◽

Cited By ~ 2

Author(s):

J Chang ◽

RH Lu ◽

SM Xu ◽

J Meneses ◽

K Chan ◽

...

Keyword(s):

Stem Cells ◽

Mouse Model ◽

Knockout Mice ◽

Globin Gene ◽

Embryonic Stem ◽

Globin Genes ◽

Human Homologue ◽

Alpha Thalassemia ◽

Alpha Globin ◽

Hemoglobin H Disease

We have disrupted the 5′ locus of the duplicated adult alpha-globin genes by gene targeting in the mouse embryonic stem cells and created mice with alpha-thalassemia syndromes. The heterozygous knockout mice (.alpha/alpha alpha) are asymptomatic like the silent carriers in humans whereas the homozygous knockout mice (.alpha/.alpha) show hemolytic anemia. Mice with three dysfunctional alpha-globin genes generated by breeding the 5′ alpha-globin knockouts (.alpha/alpha alpha) and the deletion type alpha-thalassemia mice (../alpha alpha) produce severe hemoglobin H disease and they die in utero. These results indicate that the 5′ alpha-globin gene is the predominant locus in mice, and suggest that it is even more dominant than its human homologue.

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Small gene family encoding an eggshell (chorion) protein of the human parasite Schistosoma mansoni.

Molecular and Cellular Biology ◽

10.1128/mcb.8.8.3008 ◽

1988 ◽

Vol 8 (8) ◽

pp. 3008-3016 ◽

Cited By ~ 52

Author(s):

L A Bobek ◽

D M Rekosh ◽

P T LoVerde

Keyword(s):

Schistosoma Mansoni ◽

Dna Sequences ◽

Genomic Library ◽

Regulatory Element ◽

Gene Promoter ◽

Transcription Unit ◽

Human Parasite ◽

Intergenic Dna ◽

Eggshell Proteins ◽

Silkmoth Chorion

We have isolated six independent genomic clones encoding schistosome chorion or eggshell proteins from a Schistosoma mansoni genomic library. A linkage may of five of the clones spanning 35 kilobase pair (kbp) of the S. mansoni genome was constructed. The region contained two eggshell protein genes closely linked, separated by 7.5 kbp of intergenic DNA. The two genes of the cluster were arranged in the same orientation, that is, they were transcribed from the same strand. The sixth clone probably represents a third copy of the eggshell gene that is not contained within the 35-kbp region. The 5' end of the mRNA transcribed from these genes was defined by primer extension directly off the RNA. The ATCAT cap site sequence was homologous to a silkmoth chorion PuTCATT cap site sequence, where Pu indicates any purine. DNA sequence analysis showed that there were no introns in these genes. The DNA sequences of the three genes were very homologous to each other and to a cDNA clone, pSMf61-46, differing only in three or four nucleotides. A multiple TATA box was located at positions -23 to -31, and a CAAAT sequence was located at -52 upstream of the eggshell transcription unit. Comparison of sequences in regions further upstream with silkmoth and Drosophila sequences revealed several very short elements that were shared. One such element, TCACGT, recently shown to be an essential cis-regulatory element for silkmoth chorion gene promoter function, was found at a similar position in all three organisms.

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A silencer element from the alpha-globin gene inhibits expression of beta-like genes

Molecular and Cellular Biology ◽

10.1128/mcb.8.11.5047-5051.1988 ◽

1988 ◽

Vol 8 (11) ◽

pp. 5047-5051

Author(s):

G F Atweh ◽

J M Liu ◽

H E Brickner ◽

X X Zhu

Keyword(s):

Globin Gene ◽

Expression System ◽

Globin Genes ◽

Beta Globin ◽

Base Pair Fragment ◽

Alpha Globin ◽

In Trans ◽

Cis And Trans ◽

In Cis ◽

Silencer Element

We have studied the cis and trans interactions of the alpha- and beta-globin genes in a transient expression system. We found that the alpha-globin gene inhibited beta-globin expression in cis but not in trans. The silencer element responsible for this inhibition was localized to a 259-base-pair fragment at the 5' end of the alpha-globin gene.

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