A comparative analysis of the pig, mouse, and human PCDHX genes.
ABSTRACT Protocadherin X and Y (PCDHX/Y) represent a pair of homologous genes located on the human sex chromosomes that are primarily expressed in the brain. PCDHY emerged as a result of a duplicative transposition from the X Chromosome (Chr) and is present on the Y only in hominids. Previous zoo-blot analysis suggested the existence of PCDHX orthologs on the X Chr of several mammalian species. This paper reports the cloning and characterization of porcine and murine Pcdhx. Pig Pcdhx cDNA was obtained by a combination of RT-PCR, SMART-RACE, and genomic sequencing and exhibits 88% identity to human PCDHX; FISH analysis indicated that porcine Pcdhx maps to Xq. Mouse Pcdhx cDNA was assembled by RT-PCR and database analysis and is 84% identical to the human gene. Some degree of alternative splicing was detected in pig Pcdhx, but not to the extent previously described in humans. Both murine and porcine Pcdhx mRNA were detected in all tissues studied. Cloning of 2.5 kb of genomic sequence upstream of the most 5' exon of porcine Pcdhx allowed a comparative analysis with murine and human sequences in order to define potential promoter elements. All exons present in mouse and pig transcripts were found to have homologous sequences in human DNA. Not all of these exons are represented in human transcripts, indicating differential evolution and usage. The increased complexity in post-transcriptional processing and restriction of expression of the human genes primarily to central nervous system tissue as compared with pig and mouse suggests that PCDHX/Y is potentially a good candidate to account for human-specific features of the CNS.
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ABSTRACT: Protocadherins (Pcdhs) are members of the rapidly growing cadherin superfamily and are thought to be involved in cell-cell recognition in the central nervous system. Using human BH-Pcdh cDNA, we retrieved a homologous gene from the database. The new gene (Pcdh-X, HGMW-approved symbol PCDH11) was present on a genomic clone of human chromosome X (clone bWXD306), between two sequence tagged sites, sWXD1362 and 221. Pcdh-X therefore maps to the XY homology region in Xq21.3. The open reading frame consists of 1021 amino acids (aa) including seven cadherin repeats (EC1-7) in the extracellular domain. The Pcdh-X gene consists of at least three exons; the first exon encodes the 5'-untranslated region, EC1, and half of EC2, the second exon encodes the remainder of the Pcdh-Xa, and the third exon encodes the cytoplasmic tail of Pcdh-Xb and its 3'-untranslated region. The second exon has an alternative splice site that is used to produce two isoforms with different cytoplasmic tails of 10 (Pcdh-Xa) or 14 amino acids (Pcdh-Xb). Northern blot analysis revealed an approximately 6.0-kb transcript expressed in human and mouse fetal brain.Genomics 01/2000; 62(3):540-3. · 3.01 Impact Factor
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ABSTRACT: Photoreceptor neurons (R cells) in the Drosophila visual system elaborate a precise map of visual space in the brain. The eye contains some 750 identical modules called ommatidia, each containing eight photoreceptor cells (R1-R8). Cells R1-R6 synapse in the lamina; R7 and R8 extend through the lamina and terminate in the underlying medulla. In a screen for visual behavior mutants, we identified alleles of flamingo (fmi) that disrupt the precise maps elaborated by these neurons. These mutant R1-R6 neurons select spatially inappropriate targets in the lamina. During target selection, Flamingo protein is dynamically expressed in R1-R6 growth cones. Loss of fmi function in R cells also disrupts the local pattern of synaptic terminals in the medulla, and Flamingo is transiently expressed in R8 axons as they enter the target region. We propose that Flamingo-mediated interactions between R-cell growth cones within the target field regulate target selection.Nature Neuroscience 07/2003; 6(6):557-63. · 15.25 Impact Factor
Article: Basic local alignment search tool.[show abstract] [hide abstract]
ABSTRACT: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.Journal of Molecular Biology 11/1990; 215(3):403-10. · 3.91 Impact Factor