Description:
GLUCOSE-6-PHOSPHATE DEHYDROGENASE; G6PD
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Chromosome Abnormalities |
| Class |
X Chromosome Markers |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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Black/African American
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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ISCN
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46,XX
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Passage Frozen |
9 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis and by Chromosome Analysis |
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| Gene |
G6PD |
| Chromosomal Location |
Xq28 |
| Allelic Variant 1 |
305900.0001; G6PD A+ |
| Identified Mutation |
ASN126ASP; See Kirkman et al. (1964) and Yoshida et al. (1967). Takizawa and Yoshida (1987) found that the G6PD A+ gene has an A-to-G transition, resulting in the substitution of aspartic acid for asparagine as the 142nd amino acid from the N-terminus of the enzyme. Hirono and Beutler (1988) showed that a mutation responsible for the G6PD A- phenotype present in enzyme-deficient West African and American blacks occurred in a gene that produces the G6PD A+ phenotype. A substitution of guanine for adenine at nucleotide 376 (in exon 5) was found in all G6PD A+ and G6PD A- samples but in none of the G6PD B+ samples examined. Substitution of adenine for guanine at nucleotide 202 was found in 4 of 5 G6PD A- samples; this change is apparently responsible for the in vivo instability of the enzyme protein. Thus, the difference distinguishing the A and B forms of G6PD is the amino acid at residue 126 (val68-to-met; 305900.0002). Presumably as the result of alternative splicing, there is considerable heterogeneity among different G6PD cDNAs.
Both the variant A (with enzyme activity in the normal range, also called A) and the variant A- (associated with enzyme deficiency) have a frequency of about 0.2 in several African populations. Two restriction fragment length polymorphisms have also been found in people of African descent but not in other populations, whereas a silent mutation has been shown to be polymorphic in Mediterranean, Middle Eastern, African, and Indian populations. Vulliamy et al. (1991) reported 2 additional polymorphisms detected by sequence analysis, one in intron 7 and one in intron 8. Analysis of 54 African males for the 7 polymorphic sites clustered within 3 kb of the G6PD gene showed only 7 of the 128 possible haplotypes, thus indicating marked linkage disequilibrium. These data enabled Vulliamy et al. (1991) to suggest an evolutionary pathway for the different mutations, with only a single ambiguity. The mutation underlying the A variant is the most ancient and the mutation underlying the A- variant is the most recent. Since it seemed reasonable that the A- allele is subject to positive selection by malaria, whereas the other alleles are neutral, Vulliamy et al. (1991) suggested that G6PD may lend itself to the analysis of the role of random genetic drift and selection in determining allele frequencies within a single genetic locus in human populations.
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| Remarks |
G6PD-A,PGK-1/G6PD-B,PGK-2; the majority of cells in culture express the genes for G6PD-B and PGK-2; 46,XX; 18% of cells show random chromosome loss/gain at passage 11 |
| Xu, W., Westwood, B., Bartsocas, C.S., Malcorra-Azpiazu, J.J., Indrak, K., and Beutler, E., Glucose-6 Phosphate Dehydrogenase Mutations and Haplotypes in Various Ethnic Groups Blood85(1):257-263 1995 |
| PubMed ID: 7803800 |
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| Willard HF, Breg WR, Human X chromosomes: synchrony of DNA replication in diploid and triploid fibroblasts with multiple active or inactive X chromosomes. Somatic Cell Genet6:187-98 1980 |
| PubMed ID: 6156493 |
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| Gartler SM, Chen SH, Fialkow PJ, Giblett ER, Singh S, X chromosome inactivation in cells from an individual heterozygous for two X-linked genes. Nat New Biol236:149-50 1972 |
| PubMed ID: 4502820 |
| Passage Frozen |
9 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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