HUMAN FRUCTOSE-1,6-BISPHOSPHATASE GENE (FBP1) - EXON-INTRON ORGANIZATION, LOCALIZATION TO CHROMOSOME BANDS 9Q22.2-Q22.3, AND MUTATION SCREENING IN SUBJECTS WITH FRUCTOSE-1,6-BISPHOSPHATASE DEFICIENCY

被引:60
作者
ELMAGHRABI, MR
LANGE, AJ
JIANG, W
YAMAGATA, K
STOFFEL, M
TAKEDA, J
FERNALD, AA
LEBEAU, M
BELL, GI
BAKER, L
PILKIS, SJ
机构
[1] UNIV MINNESOTA,SCH MED,DEPT BIOCHEM,MINNEAPOLIS,MN 55455
[2] SUNY STONY BROOK,DEPT PHYSIOL & BIOPHYS,STONY BROOK,NY 11794
[3] UNIV CHICAGO,DEPT BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637
[4] UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637
[5] UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637
[6] UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104
[7] UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104
关键词
D O I
10.1006/geno.1995.1085
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate. Deficiency of fructose-1,6-bisphosphatase is associated with fasting hypoglycemia and metabolic acidosis because of impaired gluconeogenesis. We have cloned and characterized the human liver fructose-1,6-bisphosphatase gene (FBP1). FBP1, localized to chromosome bands 9q22.2-q22.3 by fluorescence in situ hybridization, consists of seven exons that span >31 kb, and the six introns are in the same position as in the rat gene. FBP1 was screened for mutations in two subjects with fructose-1,6-bisphosphatase deficiency. Four nucleotide substitutions were identified, two of which were silent mutations in the codons for Ala-216 (GC (T) under bar --> GC (C) under bar and Gly-319 (GG (G) under bar --> GG (A) under bar. The other substitutions were in intron 3, a C --> T substitution 7 nucleotides downstream from the splice donor site, and in the promoter region, an A --> T substitution 188 nucleotides upstream from the start of transcription. These nucleotide substitutions were also found in normal unaffected subjects and thus are not the cause of fructose-1,6-bisphosphatase deficiency in the two subjects studied. The molecular basis of hepatic fructose-1,6-bisphosphatase deficiency in these subjects remains undetermined but could result from unidentified mutations in the promoter that decrease expression or from mutations in another gene that indirectly lead to decreased fructose-1,6-bisphosphatase activity. (C) 1995 Academic Press, Inc.
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页码:520 / 525
页数:6
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