title: The structure and organization of the human NPAT gene.
abstract: Ataxia telangiectasia (AT) is an autosomal recessive gene disorder, and ATM, a housekeeping gene, has been identified as the gene responsible for AT. Recently we found that another housekeeping gene, NPAT, is located upstream of ATM on human chromosome 11. The two housekeeping genes are transcribed in opposite directions and share a 0.5-kb 5' flanking sequence. The structure and organization of NPAT were determined by direct sequencing of cosmid clones carrying the gene and by application of the long and accurate (LA)-PCR method to amplify regions encompassing the exon/intron boundaries and all of the exons. The gene spans at least 44 kb and consists of 18 exons and 17 introns. It has been suggested that AT heterozygotes have an increased risk of developing cancer, especially breast cancer in women. Frequently, loss of heterozygosity at loci on 11q22-q24 has been observed in DNA isolated from tumors of the breast, uterine cervix, and colon, perhaps suggesting the location of a tumor suppressor gene in 11q22-q24. For investigation of the role of NPAT in AT and these tumors with allelic loss of 11q22-q24, appropriate primer sequences and PCR conditions for amplification of all the NPAT exons from genomic DNA were determined. We previously reported that no recombinations are found among Atm, Npat, and Acat1 (acetoacetyl-CoA thiolase) loci as determined by fine genetic linkage mapping of the mouse AT region. The results of the LA-PCR analysis using NPAT- and ACAT-specific primers and human genomic DNA allowed us to map ACAT 12 kb centromeric to NPAT.
authors.affiliation: Genome Research Group, National Institute of Radiological Sciences, Inage, Chiba, Japan. imait@nirs.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: T
authors.initials: T
authors.lastname: Sugawara
authors.forename: A
authors.initials: A
authors.lastname: Nishiyama
authors.forename: R
authors.initials: R
authors.lastname: Shimada
authors.forename: R
authors.initials: R
authors.lastname: Ohki
authors.forename: N
authors.initials: N
authors.lastname: Seki
authors.forename: M
authors.initials: M
authors.lastname: Sagara
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Yamauchi
authors.forename: T
authors.initials: T
authors.lastname: Hori
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D003360:Cosmids; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005091:Exons; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C101693:NPAT protein, human; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases