Cloning of the X-linked glycerol kinase deficiency gene and its identification by sequence comparison to the Bacillus subtilis homologue

Abstract

cDNA clones from a human adult testis cDNA library were isolated and sequenced as part of a programme to produce expressed sequence tags (ESTs). ESTs were used routinely to search DNA and protein sequence databases. One clone (142) showed 60% identity to the Bacillus subtilis glycerol kinase gene at both the DNA and amino acid sequence levels. Analysis of DNA from somatic cell hybrids carrying deleted X chromosomes, has shown that clone 142 detects homologous sequences between Xp21.2-p22.1 (the interval containing the locus responsible for glycerol kinase deficiency--GKD). These sequences are deleted in two patients with GKD. Clone 142 also detects homologous sequences on Xq and at several autosomal loci. The sequences of clone 142 and two further cDNA clones isolated from a human foetal brain cDNA library are presented.

Retrotransposition of Glycerol Kinase-Related Genes from the X Chromosome to Autosomes: Functional and Evolutionary Aspects

“…The highest level of mammalian GyK activity is typically found in renal and hepatic tissues; a lower level of activity is also detectable in brain, intestine, muscle, adrenal gland, fat, and, in some species, sperm (Lin, 1977;Thorner and Paulus, 1973). The GyK protein is highly conserved throughout evolution as reflected by the high degree of protein sequence identity maintained between bacteria and humans (Sargent et al, 1993).…”

AluY insertion (IVS4-52ins316alu) in the glycerol kinase gene from an individual with benign glycerol kinase deficiency

“…The hGK cDNA was cloned independently by three groups [Guo et al, 1993;Sargent et al, 1993;Walker et al, 1993]. In addition, Sargent et al [1994] reported part of the genomic organization of the Xp21 GK.…”

“…The gene for GKD was first localized to Xp21.3 by cytogenetic and molecular analysis of patients with the contiguous gene syndrome [McCabe, 1999]. The GK gene was isolated and the cDNA was cloned independently by three groups [Guo et al, 1993;Sargent et al, 1993;Walker et al, 1993]. This gene was reported to contain 19 exons and to be more than 50 kb in size, while the GK genes on chromosomes 1, 4, and Xq were intronless [Sargent et al, 1994].…”

Human testis specifically expresses a homologue of the rodent T lymphocytes RT6 mRNA

“…These observations demonstrate that only the partial sequencing associated with sequence comparison was able to establish a link among those genes. This is an efficient way to characterize new human genes as done for the human isologs of yeast suiI [25] and CDC10 [26] or for human genes involved in genetic diseases such as hereditary colon cancer [27] or X-linked glycerol kinase deficiency [28].…”