title: Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development.
abstract: Many features of Down syndrome might result from the overdosage of only a few genes located in a critical region of chromosome 21. To search for these genes, cosmids mapping in this region were isolated and used for trapping exons. One of the trapped exons obtained has a sequence very similar to part of the Drosophila single-minded (sim) gene, a master regulator of the early development of the fly central nervous system midline. Mapping data indicated that this exonic sequence is only present in the Down syndrome-critical region in the human genome. Hybridization of this exonic sequence with human fetal kidney poly(A)+ RNA revealed two transcripts of 6 and 4.3 kb. In situ hybridization of a probe derived from this exon with human and rat fetuses showed that the corresponding gene is expressed during early fetal life in the central nervous system and in other tissues, including the facial, skull, palate, and vertebra primordia. The expression pattern of this gene suggests that it might be involved in the pathogenesis of some of the morphological features and brain anomalies observed in Down syndrome.
authors.affiliation: Unité de Recherche Associée 1335 Centre National de la Recherche Scientifique, Hôpital Necker, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Dahmane
authors.forename: G
authors.initials: G
authors.lastname: Charron
authors.forename: C
authors.initials: C
authors.lastname: Lopes
authors.forename: M L
authors.initials: ML
authors.lastname: Yaspo
authors.forename: C
authors.initials: C
authors.lastname: Maunoury
authors.forename: L
authors.initials: L
authors.lastname: Decorte
authors.forename: P M
authors.initials: PM
authors.lastname: Sinet
authors.forename: B
authors.initials: B
authors.lastname: Bloch
authors.forename: J M
authors.initials: JM
authors.lastname: Delabar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002490:Central Nervous System / Q000196:embryology*; D002891:Chromosomes, Human, Pair 21; D003360:Cosmids; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics*; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D005314:Embryonic and Fetal Development; D005091:Exons; D015870:Gene Expression; D017344:Genes, Insect; D005809:Genes, Regulator; D015894:Genome, Human; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D016324:Sequence Tagged Sites
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; C089449:sim protein, Drosophila