title: ATB(0)/SLC1A5 gene. Fine localisation and exclusion of association with the intestinal phenotype of cystic fibrosis.
abstract: The Na+-dependent amino acid transporter named ATB(0) was previously found to be located in 19q13.3 by fluorescence in situ hybridisation. Genetic heterogeneity in the 19q13.2-13.4 region, syntenic to the Cystic Fibrosis Modulator Locus 1 (CFM1) in mouse, seemed to be associated to the intestinal phenotypic variation of cystic fibrosis (CF). We performed fine chromosomal mapping of ATB(0) on radiation hybrid (RH) panels G3 and TNG. Based on the most accurate location results from TNG-RH panel, mapping analysis evidenced that ATB(0) is localised between STS SHGC-13875 (D19S995) and STS SHGC-6138 in 19q13.3, that corresponds with the immediately telomeric/distal segment of the strongest linkage region within the human CFM1 (hCFM1) syntenic region. Regarding to the genomic structure and exon organisation, our results show that the ATB(0) gene is organised into eight exons. The knowledge of the genomic structure allowed us to perform an exhaustive mutational analysis of the gene. Evaluation of the possible implication of ATB(0) in the intestinal phenotype of CF was performed on the basis of the functional characteristics of the encoded protein, its apparent relevance to meconium ileus (MI) and position in relation to the hCFM1 syntenic region. We have analysed this gene in samples from CF patients with and without MI. Several sequence variations in the ATB(0) gene were identified, although none of them seemed to be related to the intestinal phenotype of CF. Even though no particular allele or haplotype in ATB(0) appears to be associated to CF-MI disease, new SNPs identified should be useful in segregation and linkage disequilibrium analyses in families affected by other disorders caused by the impairment of neutral amino acid transport.
authors.affiliation: Medical and Molecular Genetics Center-IRO, Hospital Durán i Reynals, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Larriba
authors.forename: L
authors.initials: L
authors.lastname: Sumoy
authors.forename: M D
authors.initials: MD
authors.lastname: Ramos
authors.forename: J
authors.initials: J
authors.lastname: Giménez
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: T
authors.initials: T
authors.lastname: Casals
authors.forename: V
authors.initials: V
authors.lastname: Nunes
mesh_terms: D000483:Alleles; D026962:Amino Acid Transport System ASC / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005787:Gene Frequency; D005796:Genes / Q000235:genetics; D005838:Genotype; D006801:Humans; D007415:Intestinal Obstruction / Q000150:complications; D007422:Intestines / Q000473:pathology; D007438:Introns; D008470:Meconium; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D021101:Radiation Hybrid Mapping
chemical_list: D026962:Amino Acid Transport System ASC; C505032:CFTR protein, human; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA