DSCAM: A novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system

Kazuhiro Yamakawa, Yong Kang Huo, Melissa Haendel, René Hubert, Xiao Ning Chen, Gary E. Lyons, Julie R. Korenberg

Research output: Contribution to journalArticle

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Abstract

Down syndrome (DS), a major cause of mental retardation, is characterized by subtle abnormalities of cortical neuroanatomy, neurochemistry and function. Recent work has shown that chromosome band 21q22 is critical for many of the neurological phenotypes of DS. A gene, DSCAM (Down syndrome cell adhesion molecule), has now been isolated from chromosome band 21q22.2-22.3. Homology searches indicate that the putative DSCAM protein is a novel member of the immunoglobulin (Ig) superfamily that represents a new class of neural cell adhesion molecules. The sequence of cDNAs indicates alternative splicing and predicts two protein isoforms, both containing 10 Ig-C2 domains, with nine at the N-terminus and the tenth located between domains 4 and 5 of the following array of six fibronectin III domains, with or without the following transmembrane and intracellular domains. Northern analyses reveals the transcripts of 9.7, 8.5 and 7.6 kb primarily in brain. These transcripts are differentially expressed in substructures of the adult brain. Tissue in situ hybridization analyses of a mouse homolog of the DSCAM gene revealed broad expression within the nervous system at the time of neuronal differentiation in the neural tube, cortex, hippocampus, medulla, spinal cord and most neural crest-derived tissues. Given its location on chromosome 21, its specific expression in the central nervous system and neural crest, and the homologies to molecules involved in neural migration, differentiation, and synaptic function, we propose that DSCAM is involved in neural differentiation and contributes to the central and peripheral nervous system defects in DS.

Original languageEnglish (US)
Pages (from-to)227-237
Number of pages11
JournalHuman Molecular Genetics
Volume7
Issue number2
DOIs
StatePublished - Feb 1998
Externally publishedYes

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Cell Adhesion Molecules
Down Syndrome
Nervous System
Immunoglobulins
Neural Crest
Central Nervous System
Chromosomes
Neurochemistry
Neuroanatomy
Neural Cell Adhesion Molecules
Chromosomes, Human, Pair 21
Neural Tube
Peripheral Nervous System
Brain
Alternative Splicing
Fibronectins
Intellectual Disability
Genes
In Situ Hybridization
Hippocampus

ASJC Scopus subject areas

  • Genetics

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DSCAM : A novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system. / Yamakawa, Kazuhiro; Huo, Yong Kang; Haendel, Melissa; Hubert, René; Chen, Xiao Ning; Lyons, Gary E.; Korenberg, Julie R.

In: Human Molecular Genetics, Vol. 7, No. 2, 02.1998, p. 227-237.

Research output: Contribution to journalArticle

Yamakawa, Kazuhiro ; Huo, Yong Kang ; Haendel, Melissa ; Hubert, René ; Chen, Xiao Ning ; Lyons, Gary E. ; Korenberg, Julie R. / DSCAM : A novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system. In: Human Molecular Genetics. 1998 ; Vol. 7, No. 2. pp. 227-237.
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