title: Isolation of novel genes from the CMT1A duplication/HNPP deletion critical region in 17p11.2-p12.
abstract: Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a 1.5-Mb tandem DNA duplication in chromosome 17p11.2-p12, while hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a 1.5-Mb deletion at this locus. The 1.5-Mb CMT1A monomer unit duplicated in CMT1A and deleted in HNPP is flanked by low-copy repeats termed CMT1A-REPs. Both diseases appear to be caused by an altered copy number of the peripheral myelin protein 22 gene (PMP22), which lies within the critical region. To identify additional genes rapidly, we used a cosmid contig of this region and reciprocal probing of arrayed chromosome 17-specific cosmid and cDNA libraries. Three cDNA clones were identified within the CMT1A duplication/HNPP deletion region and one just proximal to the critical region. The cDNA for human heme A:farnesyltransferase (COX10) mapped 10 kb centromeric to the distal CMT1A-REP. The other two cDNA clones from within the critical interval mapped to cosmid 126D1 at the mfd41 (D17S261) DNA marker, and their conceptual translation showed homology to 60S ribosomal protein L9 (RPL9) and chromosomal protein RMSA-1 (RMSA-1). A gene that is homologous to human peroxisome proliferator activated receptor alpha (hPPARA) was identified near the proximal CMT1A-REP.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: Z S
authors.initials: ZS
authors.lastname: Sun
authors.forename: C C
authors.initials: CC
authors.lastname: Lee
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D019883:Alkyl and Aryl Transferases; D018797:Cell Cycle Proteins; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003360:Cosmids; D018076:DNA, Complementary; D003576:Electron Transport Complex IV; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009422:Nervous System Diseases / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D014166:Transferases / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D005819:Genetic Markers; D008565:Membrane Proteins; D009687:Nuclear Proteins; C086078:RMSA-1 protein, human; D012269:Ribosomal Proteins; C049650:ribosomal protein L9; C490115:COX10 protein, human; D003576:Electron Transport Complex IV; D014166:Transferases; D019883:Alkyl and Aryl Transferases