Elsevier

Genomics

Volume 38, Issue 3, 15 December 1996, Pages 331-339
Genomics

Regular Article
Isolation of Human and Murine Homologues of theDrosophilaMinibrain Gene: Human Homologue Maps to 21q22.2 in the Down Syndrome “Critical Region”

https://doi.org/10.1006/geno.1996.0636Get rights and content

Abstract

The presence of an extra copy of human chromosome 21 (trisomy 21), especially region 21q22.2, causes many phenotypes in Down syndrome, including mental retardation. To study genes potentially responsible for some of these phenotypes, we cloned a human candidate gene (DYRK) from 21q22.2 and its murine counterpart (Dyrk) that are homologous to theDrosophilaminibrain (mnb) gene required for neurogenesis and to the rat Dyrk gene (dual specificity tyrosine phosphorylation regulated kinase). The three mammalian genes are highly conserved, >99% identical at the protein level over their 763-amino-acid (aa) open reading frame; in addition, the mammalian genes are 83% identical over 414 aa to the smaller 542-aamnbprotein. The predicted human DYRK and murineDyrkproteins both contain a nuclear targeting signal sequence, a protein kinase domain, a putative leucine zipper motif, and a highly conserved 13-consecutive-histidine repeat. Fluorescencein situhybridization and regional mapping data localize DYRK between markers D21S336 and D21S337 in the 21q22.2 region. Northern blot analysis indicated that both human and murine genes encode approximately 6-kb transcripts. PCR screening of cDNA libraries derived from various human and murine tissues indicated that DYRK andDyrkare expressed both during development and in the adult.In situhybridization ofDyrkto mouse embryos (13, 15, and 17 days postcoitus) indicates a differential spatial and temporal pattern of expression, with the most abundant signal localized in brain gray matter, spinal cord, and retina. The observed expression pattern is coincident with many of the clinical findings in trisomy 21. Its chromosomal locus (21q22.2), its homology to themnbgene, and thein situhybridization expression patterns of the murineDyrkcombined with the fact that transgenic mice for a YAC to which DYRK maps are mentally deficient suggest that DYRK may be involved in the abnormal neurogenesis found in Down syndrome.

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Sequence data from this article have been deposited with the GenBank/EMBL Data Libraries under Accession Nos. U58496 and U58497.

1

To whom correspondence should be addressed at Howard Hughes Medical Institute, MSRB I, Room 3520, 1150 W. Medical Center Drive, The University of Michigan Medical Center, Ann Arbor, MI 48109-0650. Telephone: (313) 647-4747. Fax: (313) 936-9353. E-mail:[email protected].

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