The structure of the gene ATRC1 coding for a cationic amino acid transport system in man: Molecular studies in lysinuric protein intolerance
- Federico II Univ., Naples (Italy); and others
The human cDNA (ATRC1) homologue of a murine gene encoding for a transporter specific for cationic amino acid (CAA) has been isolated. ATRC1 stimulates the uptake of CAA and shows the kinetic properties of system y+ when expressed in frog oocytes. To characterize the organization of the ATRC1 gene, a {lambda} phages genomic DNA library has been screened using an ATRC1 full length cDNA clone as a probe. Nine positive phages have been subcloned in plasmids and sequenced using cDNA specific primers to identify intron-exon junctions. The ATRC1 gene consists of 13 exons with an alternative first exon. Analysis of the intron/exon boundaries showed canonical sequences at the splice junction sites. ATRC1 expression pattern has been analyzed by RT-PCR. ATRC1 is expressed in adult fibroblasts and enterocytes, in fetal kidney, brain and heart, and in lymphoblastoid cell lines. The knowledge of structure and organization of ATRC1 can help in studying inborn errors of CAA transport. The best characterized among these diseases is Lysinuric Protein Intolerance (LPI) a multisystem disorder with impaired formation of urea and hyperammonemia after protein ingestion. Linkage analysis performed on 10 LPI patients from 9 Italian families using two intragenic RFLPs revealed 3 informative families and no recombinations. Using the CA-repeat microsatellite D12S120 (2 cM far from ATRC-1 locus) we found 7 informative families and 3 recombinational events. The sequence of the entire coding region of an LPI patient failed to show mutations. The data so far obtained do not seem to support the hypothesis that ATRC1 is the LPI gene.
- OSTI ID:
- 133842
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; CNN: Grant E.09; TRN: 95:005313-0575
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Characterization of a protein kinase gene in allelic association with the spinal muscular atrophy locus
Three RFLPs defining a haplotype associated with the common mutation in a human medium-chain acyl-CoA dehydrogenase (MCAD) deficiency occur in Alu repeats