Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down Syndrome Candidate Region 1) gene

J. J. Fuentes, M. A. Pritchard, Xavier P. Estivill

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Down syndrome is a major cause of mental retardation and congenital heart defects and is due to the presence of three copies of human chromosome 21 in the affected individual. We have identified a gene, DSCR1 (HGMW- approved symbol), from the region 21q22.1-q22.2, which is highly expressed in human fetal brain and adult heart. Structural features of the conceptual protein encourage us to propose involvement of DSCR1 in the regulation of transcription and/or signal transduction. Higher expression of RNA in the brains of young rats compared to adults suggests a possible role for the gene in the development of the central nervous system. We have determined the genomic organization of DSCR1 and identified three additional alternative first exons by RACE and cDNA library screening. DSCR1 spans nearly 45 kb of genomic DNA and comprises seven exons, four of which (exons 1-4) are alternative first exons. All the exons are flanked by splice junctions that conform to the consensus AG-GT motif. We have studied the expression patterns of the alternative first exons. Exon 2 was detected in fetal brain and liver by RT-PCR. Both exons 1 and 4 were differentially expressed in fetal brain, lung, liver, and kidney and in all adult tissues tested by Northern analysis with two notable exceptions: exon 1 was not detected in adult kidney and exon 4 was not found in adult brain. The high level of expression of exon 1 in fetal brain suggests that this alternative form of DSCR1 has an important role in brain development. This information should help us to understand the possible relationship of DSCR1 with Down syndrome and aid in the development of animal models.

Original languageEnglish
Pages (from-to)358-361
Number of pages4
JournalGenomics
Volume44
Issue number3
DOIs
Publication statusPublished - 15 Sep 1997
Externally publishedYes

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Alternative Splicing
Down Syndrome
Exons
Genes
Brain
Kidney
Chromosomes, Human, Pair 21
Congenital Heart Defects
Liver
Human Chromosomes
Gene Library
Intellectual Disability
Signal Transduction
Consensus
Central Nervous System
Animal Models
RNA
Polymerase Chain Reaction
Lung

ASJC Scopus subject areas

  • Genetics

Cite this

Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down Syndrome Candidate Region 1) gene. / Fuentes, J. J.; Pritchard, M. A.; Estivill, Xavier P.

In: Genomics, Vol. 44, No. 3, 15.09.1997, p. 358-361.

Research output: Contribution to journalArticle

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