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G Vaca

Publications and source records attributed to G Vaca.

At least 19 recordsLinked to original sources
PubMed2000

Glucose-6-phosphate dehydrogenase mutations and haplotypes in Mexican Mestizos.

In a screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 1985 unrelated male subjects from the general population (Groups A and B) belonging to four states of the Pacific coast, 21 G-6-PD-deficient subjects were detected. Screening for mutations at the G-6-PD gene by PCR-restriction enzyme in these 21 G-6-PD-deficient subjects as well as in 14 G-6-PD-deficient patients with hemolytic anemia belonging to several states of Mexico showed two common G-6-PD variants: G-6-PD A-(202A/376G) (19 cases) and G-6-PD A-(376G/968C) (9 cases). In 7 individuals the mutations responsible for the enzyme deficiency remain to be determined. Furthermore, four silent polymorphic sites at the G-6-PD gene (PvuII, PstI, 1311, and NlaIII) were investigated in the 28 individuals with G-6-PD A- variants and in 137 G-6-PD normal subjects. As expected, only 10 different haplotypes were observed. To date, in our project aiming to determine the molecular basis of G-6-PD deficiency in Mexico, 60 unrelated G-6-PD-deficient Mexican males-25 in previous studies and 35 in the present work-have been studied. More than 75% of these individuals are from states of the Pacific coast (Sinaloa, Nayarit, Jalisco, Michoacán, Guerrero, Oaxaca, and Chiapas). The results show that although G-6-PD deficiency is heterogeneous at the DNA level in Mexico, only three polymorphic variants have been observed: G-6-PD A-(202A/376G) (36 cases), G-6-PD A-(376G/968C) (13 cases), and G-6-PD Seattle(844C) (2 cases). G-6-PD A- variants are relatively distributed homogeneously and both variants explain 82% of the overall prevalence of G-6-PD deficiency. The variant G-6-PD A-(202A/376G) represents 73% of the G-6-PD A- alleles. Our data also show that the variant G-6-PD A-(376G/968C)-which has been observed in Mexico in the context of two different haplotypes-is more common than previously supposed. The three polymorphic variants that we observed in Mexico are on the same haplotypes as found in subjects from Africa, the Canary Islands, and Spain.

DNA↗
PubMed1997

Molecular genetics of glucose-6-phosphate dehydrogenase deficiency in Mexico.

Several studies carried out between 1965 and 1985 showed that G-6-PD deficiency in Mexico is heterogeneous at the biochemical level and that the G-6-PD A- phenotype is relatively common. We have now investigated the molecular basis of G-6-PD deficiency in Mexico. Up-to-date 60 chromosomes with G6PD mutations have been studied, 16 in previous studies and 44 in the present work. Molecular analysis of DNA from G-6-PD deficient Mexican mestizos and their relatives show that G-6-PD A- genotypes are relatively common but also that in Mexico G-6-PD deficiency is heterogeneous at the DNA level. Thus, five different genotypes have been observed: G-6-PD A-(202A/376G) (41 chromosomes), G-6-PD A-(376G/968C) (14 chromosomes), G-6-PD Seattle844C (3 chromosomes), G-6-PD "Mexico City"680A (1 chromosome) and G-6-PD Guadalajara1159T (1 chromosome). The G-6-PD A-(202A/376G), G-6-PD A-(376G/968C) and G-6-PD Seattle844C mutations in Mexico are on the same Pvu II/ Pst I/ 1311 / Nla III haplotypes as found in individuals from Africa, Spain and the Canary Islands. Consequently, these mutations were probably imported to Mexico through African slaves and/or the Spanish immigrants during and after the colonization.

Adult↗
PubMed1995

Structural organization of the human sorbitol dehydrogenase gene (SORD).

The primary structure of human sorbitol dehydrogenase (SORD) was determined by cDNA and genomic cloning. The nucleotide sequence of the mRNA covers 2471 bp including an open reading frame that yields a protein of 356 amino acid residues. The gene structure of SORD spans approximately 30 kb divided into 9 exons and 8 introns. The gene was localized to chromosome 15q21.1 by in situ hybridization. Two transcription initiation sites were detected. Three Sp1 sites and a repetitive sequence (CAAA)5 were observed in the 5' noncoding region; no classical TATAA or CCAAT elements were found. The related alcohol dehydrogenases and zeta-crystallin have the same gene organization split by 8 introns, but no splice points coincide between SORD and these gene types. The deduced amino acid sequence of the SORD structure differs at a few positions from the directly determined protein sequence, suggesting allelic forms of the enzyme. High levels of SORD transcripts were observed in lens and kidney, as judged from Northern blot analysis.

Amino Acid Sequence↗
PubMed1995

Molecular heterogeneity of G-6-PD deficiency in Mexico.

DNA samples from seven G-6-PD deficient Mexican mestizo patients were analyzed. Three different G-6-PD genotypes were observed: G-6-PD A-202A/376G (three patients), G-6-PD A-376G/968C (three patients) and G-6-PD Seattle844C. The present results, along with previous reports, suggest not only G-6-PD A-genotypes are relatively common but also G-6-PD deficiency seems to be heterogeneous at DNA level in Mexico.

Africa↗
PubMed1993

Membrane-bound sorbitol dehydrogenase in human red blood cells. Studies in normal subjects and in enzyme-deficient subjects with congenital cataracts.

Membrane-bound and soluble forms of erythrocyte sorbitol dehydrogenase (SORD) activity are compared in normal individuals. Both isoenzymes showed similar properties. In a family with red cell SORD deficiency and congenital cataracts, Km values for sorbitol and NAD+ as well as the effect of the enzymatic deficiency on sorbitol accumulation in red cells incubated in high-glucose or high-fructose media were determined. In SORD-deficient patients, the enzymatic deficiency was observed in both crude haemolysate and SORD-M preparations with sorbitol, galactitol, xylitol or ribitol as substrates. The mutation responsible for SORD deficiency did not modify the Km for sorbitol and NAD+. Finally, SORD deficiency produced a significant increase of sorbitol accumulation in red cells incubated in high-concentration glucose media and a significant decrease when the cells were incubated in high-concentration fructose media.

Cataract↗
PubMed1992

New glucose-6-phosphate dehydrogenase mutations from various ethnic groups.

Seven new mutations that produce glucose 6 phosphate dehydrogenase (G6PD) deficiency are described. Three are in variants that were biochemically characterized and described previously, while four were found in samples that had not been characterized biochemically. Several of the mutations affect the amino acids that are mutated in other G6PD variants. As had been noted previously, variants that are associated with nonspherocytic anemia are located either near the glucose 6 phosphate or the NADP binding sites. Variants more distant from these sites are not associated with chronic hemolysis.

Amino Acid Sequence↗
PubMed1992

Effects of G-6-PD deficiency, experimentally induced or genetically transmitted, on the sorbitol pathway activity. In vitro and in vivo studies.

Aldose reductase catalyzes the NADPH-linked reduction of hexoses to their respective sugar-alcohols, which are involved in the pathogenesis of "sugar-cataracts". In the lenses, the reaction catalyzed by G-6-PD is the source of NADPH supply blocking sugar-alcohol formation and consequently prevents or delays the onset of "sugar-cataracts". We have investigated the effect of G-6-PD deficiency, either experimentally induced or genetically transmitted, on the sorbitol accumulation in whole cells incubated in high glucose media and on the "sugar-cataracts" formation in a galactosemic rat model. We also screened 31 Negro male adults with diabetes mellitus for red cell G-6-PD deficiency. G-6-PD deficiency produced a significant inhibition on sorbitol accumulation in rat lenses and human red cells incubated in 50 mM glucose. In the galactosemic rat model G-6-PD deficiency experimentally induced with acetaminophen delayed the development of cataracts. Finally, two diabetic individuals were G-6-PD deficient and did not show cataracts whereas cataracts were identified in six other diabetic patients.

Acetaminophen↗
PubMed1990

[Effect of gene dosage on the glyceraldehyde-3-phosphate dehydrogenase enzyme (GAPD) in partial 12p13.3 pter trisomy].

A family with three brothers presenting 12p trisomy due to an adjacent-1 segregation of a paternal translocation (1;12) (q44;p12.2) is described. The patient's phenotype was compatible with the chromosomal imbalance including the gene dosage effect of the glyceraldehyde-3-phosphate dehydrogenase. The importance of the genetic counseling in these families is stressed.

Abnormalities, Multiple↗
PubMed1989

Reduced levels of uridine diphosphate glucose pyrophosphorylase activity in fetal and neonatal human and guinea pig liver.

Uridine diphosphate glucose pyrophosphorylase (UDPGPP) is the first enzyme in the bilirubin conjugation pathway. A study aiming to screen for red blood cell UDPGPP deficiency in newborns with hyperbilirubinemia was carried out. No individuals with severe UDPGPP deficiency were found, however, levels of UDPGPP in premature and at term newborns were lower than in adults. These findings led to the study of UDPGPP in human fetal, neonatal and adult liver, using guinea pig tissues as a parallel control. UDPGPP activities in fetal and neonatal samples were also significantly lower than in adult ones in both species. Therefore, it is postulated that the reduced levels of UDPGPP in fetal and neonatal liver could be a factor which contributes to the pathogenesis of the physiologic jaundice in human newborns.

Animals↗
PubMed1989

Electrophoretic pattern of sorbitol dehydrogenase (E.C.1.1.1.14) in human seminal plasma and spermatozoa.

An electrophoretic study of sorbitol dehydrogenase (SORD) in sperm and seminal plasma (SP) was realized. In SP, three phenotypes (one slow band, one fast, and both bands) were observed, corroborating the electrophoretic variability of SP-SORD formerly reported by us, while, in sperm, SORD showed a phenotype of one band faster than the one of SP. Biochemical studies showed that thiol groups participate in the mobility of the SP fast band; furthermore, an interchange of the bands of SP-SORD was observed which suggests that the isozymes are due to conformational isomerism or to molecular aggregates.

Electrophoresis, Polyacrylamide Gel↗
PubMed1989

Screening for thermostability and electrophoretic red blood cell sorbitol dehydrogenase (E.C.1.1.1.14) variants.

A screening for both thermostability and electrophoretic red blood cell sorbitol dehydrogenase (RBC-SORD) variants in blood donors was performed. SORD activity in standard conditions (unheated samples) in 274 individuals was 198 +/- 38.6 mIU/g Hb. The ratio of enzymatic activity after heating (H) to the activity in controls (C) before heating (H/C ratio) was 0.39 +/- 0.10. H/C ratios minor than 0.1 in 3 out of 274 blood donors and higher than 0.9 in 1 were observed. In 208 individuals, four electrophoretic phenotypes were observed: I) Three bands, named a, b and c, with cathodic mobility in 163 individuals (78.36%); II) Two bands a and c in 25 individuals (12.02%); III) Two bands b and c in 14 (6.73%); and IV) One band, c in 6 (2.88%). Studies carried out to characterize the three bands suggest that they are isozymes of the same locus with the observation of an interchange of the bands as a normal phenomena.

Electrophoresis, Disc↗
PubMed1988

Genetic heterogeneity of thalassemias in Mexican mestizo patients with hemolytic anemia.

Twenty-eight Hb abnormalities (16 thalassemias, 10 Hb variants and 2 hereditary persistences of fetal hemoglobin) were detected in an etiopathogenic search in 131 patients with hemolytic anemia. The observed thalassemic genotypes [6 beta(0)/beta, 2 (delta beta) (0)/beta(0), 2 beta(0)/beta(+), 2 beta(0)/beta(s), 2 beta(+)/beta(+), 1 beta(+)/beta(s) and 1 (delta beta)(0)/beta] showed heterogeneity in the population studied. A native origin of some of these mutations is considered.

Anemia, Hemolytic↗
PubMed1987

Centric fission, centromere-telomere fusion and isochromosome formation: a possible origin of a de novo 12p trisomy.

A 5-month-old girl had a typical 12p trisomy syndrome due to a monocentric i(12p) present in a 46-chromosome complement that also included the translocation of all 12q onto the 8p telomere; i.e., her complex karyotype could be written as 46,XX,-8,-12, +der(8),t(8;12)(p23.3;cen),+i(12p). The present concurrence of a whole-arm q translocation and an i(p) for a single chromosome, along with six previous similar instances involving chromosomes 4, 5 and 9, suggests the following origin for such a special rearrangement: a centric fission in G1 initially yielding two telocentrics; at the next replication, the tel(q) translocates onto a nonhomologous telomere (centromere-telomere fusion), whereas the tel(p) becomes an i(p). This mechanism can be either meiotic or postzygotic and surmises that the translocated long arm retains a partial centromere, which subsequently is inactivated and loses its staining properties.

Abnormalities, Multiple↗
PubMed1987

Screening for red blood cell sorbitol dehydrogenase deficiency in patients with diabetes or cataracts.

Quantitative screening for red blood cell sorbitol dehydrogenase (RBC-SORD) deficiency in 111 patients with juvenile onset diabetes, 92 patients with adult onset diabetes, 42 patients with idiopathic cataracts and 192 professional blood donors was performed. A wide variability in RBC-SORD activity in controls and patients was observed. No significant differences in SORD activity either between patients with diabetes and patients with idiopathic cataracts or between diabetics with and without cataracts were observed. Whether or not there were carriers for either amorphous or hypomorphous alleles of the SORD locus in the population studied could not be defined in terms of enzymatic activity levels.

Cataract↗
PubMed1986

Bloom syndrome in a Mexican mestizo girl.

A 3-year-old girl with Bloom syndrome is described. She exhibited stunted growth of prenatal onset and defective immunity, but the typical skin manifestations were absent. Cytogenetic analysis revealed a 46,XX complement, 12.2% of metaphases with at least a structural aberration, and a ten-fold increase in the sister-chromatid exchange rate. Leukocyte beta-glucuronidase activity was reduced to about 1/3; the significance of this finding is not clear. The present observation demonstrates the variable expression of the disorder probably depending on ethnic and constitutional factors.

Bloom Syndrome↗
PubMed1985

G-6-PD Jalisco and G-6-PD Morelia: two new Mexican variants.

Two new G-6-PD variants designated G-6-PD Jalisco and G-6-PD Morelia were identified in two unrelated Mexican families. An additional G-6-PD variant was found in each family: G-6-PD Trinacria and G-6-PD A-. In both families compound heterozygotes were identified. G-6-PD Jalisco and G-6-PD Morelia belong to Classes 3 and 4, respectively. G-6-PD Morelia is the first variant from its class with a high Km for NADP and a low Ki for NADPH.

Adult↗