Population genetics of human glyoxalases

Thornalley, Paul J.

doi:10.1038/hdy.1991.73

Cited by 24 publications

(19 citation statements)

References 20 publications

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“…There is also one report on the association of a depression locus to the GLO1 gene [Tanna et al, 1989]. The Glu111 variant in the present study that showed increased acidic mobility in the twodimensional gel analysis is same as that reported by Goldman et al [1991] and Thornalley [1991].…”

Section: Resultssupporting

confidence: 90%

“…The allele frequency of A419 in autism and control samples is0.6056 and 0.44, respectively, a highly significant difference (one-tailed Fisher's Test P < 0.0079). Numerous reports of GLO1 allele frequency (for Glu-Glo1) in different populations across the world and in the United States showed values between 0.306 and 0.49 [Goldman et al, 1991;Thornalley, 1991]. Our analysis of GLO1 (Glu-Glo1) allele frequency in controls also falls within this range.…”

Section: Resultssupporting

confidence: 75%

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Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Junaid

Kowal

Barua

et al. 2004

American J of Med Genetics Pt A

144

122

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Autism is a neurodevelopmental disability characterized by deficits in verbal communications, impairments in social interactions, and repetitive behaviors. Several studies have indicated strong involvement of multigenic components in the etiology of autism. Linkage analyses and candidate gene search approaches so far have not identified any reliable susceptibility genes. We are using a proteomic approach to identify protein abnormalities due to aberrant gene expression in autopsied autism brains. In four of eight autism brains, we have found an increase in polarity (more acidic) of glyoxalase I (Glo1) by two-dimensional gel electrophoresis. To identify the molecular change resulting in the shift of Glo1 polarity, we undertook sequencing of GLO1 gene. Direct sequencing of GLO1 gene/mRNA in these brains, has identified a single nucleotide polymorphism (SNP), C419A. The SNP causes an Ala111Glu change in the protein sequence. Population genetics of GLO1 C419A SNP studied in autism (71 samples) and normal and neurological controls (49 samples) showed significantly higher frequency for the A419 (allele frequency 0.6 in autism and 0.4 in controls, one-tailed Fisher's test P < 0.0079). Biochemical measurements have revealed a 38% decrease in Glo1 enzyme activity in autism brains (one-tailed t-test P < 0.026). Western blot analysis has also shown accumulation of advanced glycation end products (AGE's) in autism brains. These data suggest that homozygosity for A419 GLO1 resulting in Glu111 is a predisposing factor in the etiology of autism.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 75%

Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Junaid

Kowal

Barua

et al. 2004

American J of Med Genetics Pt A

144

122

View full text Add to dashboard Cite

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“…Glo1 is diallelic with each allele coding for a 21.5 kDa subunit of Glo1 dimer protein, running at 23 kDa in SDS-PAGE [15]. A rare polymorphism produces genotypes Glo1a (common) and Glo1b (rare) which, like human GLO1, gives rise to allozymes of similar molecular mass and enzymatic activity [16,17]. The IMKC Glo1 mutant mouse was produced by gene trapping, with retroviral insertion of vector VICTR48 between exons-1 and -2 in strain 129SvEv Brd -derived mESCs and bred in a C57BL/6J background.…”

Section: Introductionmentioning

confidence: 99%

Reappraisal of putative glyoxalase 1-deficient mouse and dicarbonyl stress on embryonic stem cellsin vitro

Shafie

Xue

Barker

et al. 2016

Biochemical Journal

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Glyoxalase 1 (Glo1) is a cytoplasmic enzyme with a cytoprotective function linked to metabolism of the cytotoxic side product of glycolysis, methylglyoxal (MG). It prevents dicarbonyl stress — the abnormal accumulation of reactive dicarbonyl metabolites, increasing protein and DNA damage. Increased Glo1 expression delays ageing and suppresses carcinogenesis, insulin resistance, cardiovascular disease and vascular complications of diabetes and renal failure. Surprisingly, gene trapping by the International Mouse Knockout Consortium (IMKC) to generate putative Glo1 knockout mice produced a mouse line with the phenotype characterised as normal and healthy. Here, we show that gene trapping mutation was successful, but the presence of Glo1 gene duplication, probably in the embryonic stem cells (ESCs) before gene trapping, maintained wild-type levels of Glo1 expression and activity and sustained the healthy phenotype. In further investigation of the consequences of dicarbonyl stress in ESCs, we found that prolonged exposure of mouse ESCs in culture to high concentrations of MG and/or hypoxia led to low-level increase in Glo1 copy number. In clinical translation, we found a high prevalence of low-level GLO1 copy number increase in renal failure where there is severe dicarbonyl stress. In conclusion, the IMKC Glo1 mutant mouse is not deficient in Glo1 expression through duplication of the Glo1 wild-type allele. Dicarbonyl stress and/or hypoxia induces low-level copy number alternation in ESCs. Similar processes may drive rare GLO1 duplication in health and disease.

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“…HAGH1 is electrophoretically "slow" and HAGH2 "fast" (8,9). However, the two isoforms of distinctive isoelectric point are not resolved.…”

Section: Component Of the Glyoxalase System Which Catalyses The Convementioning

confidence: 99%

“…However, a rare second form, HAGH2, has been found in Micronesian (7) and Japanese (8) populations. The population genetics of human glyoxalases have recently been reviewed (9).…”

Section: Component Of the Glyoxalase System Which Catalyses The Convementioning

confidence: 99%

Electrophoretic Analysis of Isoforms of Glyoxalase II in Clinical Blood Samples

McLellan¹,

Thornalley²

1992

Clinical Chemistry and Laboratory Medicine

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Summary:A non-denaturing polyacrylamide gel electrophoresis procedure is described for the analysis of isoforms of human red blood cell glyoxalase II (EC 3.1.2.6). A cathodic, continuous buffer electrophoresis system was developed, using a 60 g/1 polyacrylamide gel with 25 g/1 N^-methylene-bis-acrylamide in 50 mmol/1 sodium succinate buffer, pH 5.5 and 1 °C. Staining for glyoxalase II activity involved

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Population genetics of human glyoxalases

Cited by 24 publications

References 20 publications

Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Reappraisal of putative glyoxalase 1-deficient mouse and dicarbonyl stress on embryonic stem cellsin vitro

Electrophoretic Analysis of Isoforms of Glyoxalase II in Clinical Blood Samples

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