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Title: Localization of a renal sodium-phosphate cotransporter gene to human chromosome 5q35

Abstract

Several Mendelian disorders of renal phosphate reabsorption, associated with hypophosphatemia and bone disease, have been described. These include X-linked hypophosphatemia (XLH), hereditary hypophosphatemic rickets with hypercalciuria, hypophosphatemic bone disease, and autosomal dominant and autosomal recessive hypophosphatemic rickets. The underlying mechanisms for renal phosphate wasting in these disorders remain unknown. The proximal tubule is the major site of renal phosphate reabsorption. Thus, mutations in genes that participate in the transepithelial transport of phosphate in this segment of the nephron may be responsible for these disorders. Recently, a cDNA encoding a renal proximal tubular, brush-border membrane Na[sup +]-phosphate cotransporter (NaP[sub i]-3) was cloned from human kidney cortex. As a first step in establishing whether mutations in the NaP[sub i]-3 gene are the cause of inherited disorders in phosphate homeostasis, the authors sought to determine its chromosomal localization. 9 refs., 1 fig.

Authors:
;  [1]; ;  [2];  [3];  [4]
  1. (McGill Univ., Montreal (Canada))
  2. (Universite de Montreal, Quebec (Canada))
  3. (Duke Univ., Durham, NC (United States))
  4. (Univ. of Zurich (Switzerland))
Publication Date:
OSTI Identifier:
6860379
Resource Type:
Journal Article
Resource Relation:
Journal Name: Genomics; (United States); Journal Volume: 19:1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HUMAN CHROMOSOME 5; GENETIC MAPPING; PHOSPHORUS; METABOLIC DISEASES; PORINS; GENES; KIDNEYS; BODY; CHROMOSOMES; DISEASES; ELEMENTS; HUMAN CHROMOSOMES; MAPPING; MEMBRANE PROTEINS; NONMETALS; ORGANIC COMPOUNDS; ORGANS; PROTEINS 550400* -- Genetics

Citation Formats

Kos, C.H., Tenenhouse, H.S., Tihy, F., Lemieux, N., Econs, M.J., and Murer, H. Localization of a renal sodium-phosphate cotransporter gene to human chromosome 5q35. United States: N. p., 1994. Web. doi:10.1006/geno.1994.1034.
Kos, C.H., Tenenhouse, H.S., Tihy, F., Lemieux, N., Econs, M.J., & Murer, H. Localization of a renal sodium-phosphate cotransporter gene to human chromosome 5q35. United States. doi:10.1006/geno.1994.1034.
Kos, C.H., Tenenhouse, H.S., Tihy, F., Lemieux, N., Econs, M.J., and Murer, H. 1994. "Localization of a renal sodium-phosphate cotransporter gene to human chromosome 5q35". United States. doi:10.1006/geno.1994.1034.
@article{osti_6860379,
title = {Localization of a renal sodium-phosphate cotransporter gene to human chromosome 5q35},
author = {Kos, C.H. and Tenenhouse, H.S. and Tihy, F. and Lemieux, N. and Econs, M.J. and Murer, H.},
abstractNote = {Several Mendelian disorders of renal phosphate reabsorption, associated with hypophosphatemia and bone disease, have been described. These include X-linked hypophosphatemia (XLH), hereditary hypophosphatemic rickets with hypercalciuria, hypophosphatemic bone disease, and autosomal dominant and autosomal recessive hypophosphatemic rickets. The underlying mechanisms for renal phosphate wasting in these disorders remain unknown. The proximal tubule is the major site of renal phosphate reabsorption. Thus, mutations in genes that participate in the transepithelial transport of phosphate in this segment of the nephron may be responsible for these disorders. Recently, a cDNA encoding a renal proximal tubular, brush-border membrane Na[sup +]-phosphate cotransporter (NaP[sub i]-3) was cloned from human kidney cortex. As a first step in establishing whether mutations in the NaP[sub i]-3 gene are the cause of inherited disorders in phosphate homeostasis, the authors sought to determine its chromosomal localization. 9 refs., 1 fig.},
doi = {10.1006/geno.1994.1034},
journal = {Genomics; (United States)},
number = ,
volume = 19:1,
place = {United States},
year = 1994,
month = 1
}
  • This report describes the localization of the human ileal sodium-bile acid cotransporter gene (SLC10A2) to human chromosome 13q33 using fluorescence in situ hybridization. The article discusses some possible roles for this gene in inherited disorders of bile acid and cholesterol metabolism. 9 refs., 1 fig.
  • A human Na{sup +}/myo-inositol cotransporter (SLC5A3) gene was cloned; sequencing revealed a single intron-free open reading frame of 2157 nucleotides. Containing 718 amino acid residues, the predicted protein is highly homologous to the product of the canine osmoregulatory SLC5A3 gene. The SLC5A3 protein is number 3 of the solute carrier family 5 and was previously designated SMIT. Using fluorescence in situ hybridization, the human SLC5A3 gene was localized to band q22 on chromosome 21. Many tissues including brain demonstrate gene expression. The inability of a trisomic 21 cell to downregulate expression of three copies of this osmoregulatory gene could resultmore » in increased flux of both myo-inositol and Na{sup +} across the plasma membrane. The potential consequences include perturbations in the cell membrane potential and tissue osmolyte levels. The SLC5A3 gene may play a role in the pathogenesis of Down syndrome. 54 refs., 4 figs.« less
  • The chromosomal location of the gene SGLT2, which is presumed to encode a low-affinity Na[sup +]/glucose cotransporter, has been determined using a panel of rodent-human somatic cell hybrids. Southern blot analysis of genomic DNA from 16 different hybrids shows that SGLT2 is located on chromosome 16. Analysis of three additional hybrids that selectively retain all or part of human chromosome 16 demonstrates that SGLT2 is located close to the centromere in band p11.2 of the chromosome. 7 refs., 1 fig., 1 tab.
  • Resorption of phosphate by the kidney is an important function in the maintenance of phosphate homeostasis in mammals, and a defect in renal phosphate uptake has been implicated in at least three human genetic disorders. The authors have isolated a cDNA encoding a human sodium-dependent phosphate transport protein (NPT1). This cDNA hybridizes to a single 2.5-kb RNA transcript from human kidney cortex, its nucleotide sequence shows 80.3% identity to the rabbit NaPi-1 sequence, and it encodes a polypeptide of 467 amino acids. Amino acid sequence comparisons indicate a 69.7% identity between human NPT1 and rabbit NaPi-1 polypeptides; the inclusion ofmore » conservative substitutions increases the homology between the two proteins to 81.5%. Alignment of both sequences also reveals several conserved potential N-glycosylation and protein kinase C phosphorylation sites. Polypeptide hydropathy analysis predicts several membrane-spanning domains. This cDNA maps the location of the gene encoding NPT1 to human chromosome 6p21.3-p23. 24 refs., 4 figs.« less
  • The Na[sup +]/glucose cotransporter gene SGLT1 encodes the primary carrier protein responsible for the uptake of the dietary sugars glucose and galactose from the intestinal lumen. SGLT1 transport activity is currently exploited in oral rehydration therapy. The 75-kDa glycoprotein is localized in the brush border of the intestinal epithelium and is predicted to comprise 12 membrane spans. In two patients with the autosomal recessive disease glucose/galactose malabsorption, the underlying cause was found to be a missense mutation in SGLT1, and the Asp28 [yields] Asn change was demonstrated in vitro to eliminate SGLT1 transport activity. The SGLT1 gene was previously shownmore » to reside on the distal q arm of chromosome 22(11.2 [yields] qter). The authors have used a cosmid probe for fluorescence in situ hybridization, which refines the localization to 22q13.1, and provide an example of the utility of the SGLT1 probe as a diagnostic for genetic diseases associated with trans-locations of chromosome 22. 18 refs., 2 figs.« less