Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain

Challenging the gene dosage effect hypothesis (Part II)

M. S. Cheon, M. Bajo, S. H. Kim, J. O. Claudio, Alexander Keith Stewart, D. Patterson, W. D. Kruger, H. Kondoh, Gert Lubec

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Down syndrome (DS) is the most common genetic cause of mental retardation. To explain the impact of extra chromosome 21 in the pathology of DS, gene dosage effect hypothesis has been proposed, but several investigators including our group have challenged this hypothesis. Although analysis of the sequence of chromosome 21 has been essentially completed, the molecular and biochemical mechanisms underlying the pathology are still unknown. We therefore investigated expression levels of six proteins encoded on chromosome 21 (HACS1, DYRK1A, αA-crystallin, FTCD, GARS-AIRS-GART, and CBS) in fetal cerebral cortex from DS and controls at 18-19 weeks of gestational age using Western blot analysis. Protein expression of HACS1 was significantly and remarkably decreased in DS, and the expression levels of five proteins were comparable between DS and controls suggesting that the gene dosage effect hypothesis is not sufficient to fully explain the DS phenotype. We are continuing to quantify proteins whose genes are encoded on chromosome 21 in order to provide a better understanding of the pathobiochemistry of DS at the protein level.

Original languageEnglish (US)
Pages (from-to)119-125
Number of pages7
JournalAmino Acids
Volume24
Issue number1-2
StatePublished - Mar 2003
Externally publishedYes

Fingerprint

Chromosomes, Human, Pair 21
Gene Dosage
Chromosomes
Down Syndrome
Brain
Genes
Pathology
Proteins
Crystallins
Intellectual Disability
Cerebral Cortex
Gestational Age
Sequence Analysis
Western Blotting
Research Personnel
Phenotype

Keywords

  • AlphaA-crystallin
  • CBS
  • Chromosome 21
  • Down syndrome
  • DYRK1A
  • FTCD
  • GARS-AIRS-GART
  • HACS1

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry
  • Endocrinology

Cite this

Cheon, M. S., Bajo, M., Kim, S. H., Claudio, J. O., Stewart, A. K., Patterson, D., ... Lubec, G. (2003). Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: Challenging the gene dosage effect hypothesis (Part II). Amino Acids, 24(1-2), 119-125.

Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain : Challenging the gene dosage effect hypothesis (Part II). / Cheon, M. S.; Bajo, M.; Kim, S. H.; Claudio, J. O.; Stewart, Alexander Keith; Patterson, D.; Kruger, W. D.; Kondoh, H.; Lubec, Gert.

In: Amino Acids, Vol. 24, No. 1-2, 03.2003, p. 119-125.

Research output: Contribution to journalArticle

Cheon, MS, Bajo, M, Kim, SH, Claudio, JO, Stewart, AK, Patterson, D, Kruger, WD, Kondoh, H & Lubec, G 2003, 'Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: Challenging the gene dosage effect hypothesis (Part II)', Amino Acids, vol. 24, no. 1-2, pp. 119-125.
Cheon, M. S. ; Bajo, M. ; Kim, S. H. ; Claudio, J. O. ; Stewart, Alexander Keith ; Patterson, D. ; Kruger, W. D. ; Kondoh, H. ; Lubec, Gert. / Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain : Challenging the gene dosage effect hypothesis (Part II). In: Amino Acids. 2003 ; Vol. 24, No. 1-2. pp. 119-125.
@article{6bad42f6c1004fac8b9016eaedc72678,
title = "Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: Challenging the gene dosage effect hypothesis (Part II)",
abstract = "Down syndrome (DS) is the most common genetic cause of mental retardation. To explain the impact of extra chromosome 21 in the pathology of DS, gene dosage effect hypothesis has been proposed, but several investigators including our group have challenged this hypothesis. Although analysis of the sequence of chromosome 21 has been essentially completed, the molecular and biochemical mechanisms underlying the pathology are still unknown. We therefore investigated expression levels of six proteins encoded on chromosome 21 (HACS1, DYRK1A, αA-crystallin, FTCD, GARS-AIRS-GART, and CBS) in fetal cerebral cortex from DS and controls at 18-19 weeks of gestational age using Western blot analysis. Protein expression of HACS1 was significantly and remarkably decreased in DS, and the expression levels of five proteins were comparable between DS and controls suggesting that the gene dosage effect hypothesis is not sufficient to fully explain the DS phenotype. We are continuing to quantify proteins whose genes are encoded on chromosome 21 in order to provide a better understanding of the pathobiochemistry of DS at the protein level.",
keywords = "AlphaA-crystallin, CBS, Chromosome 21, Down syndrome, DYRK1A, FTCD, GARS-AIRS-GART, HACS1",
author = "Cheon, {M. S.} and M. Bajo and Kim, {S. H.} and Claudio, {J. O.} and Stewart, {Alexander Keith} and D. Patterson and Kruger, {W. D.} and H. Kondoh and Gert Lubec",
year = "2003",
month = "3",
language = "English (US)",
volume = "24",
pages = "119--125",
journal = "Amino Acids",
issn = "0939-4451",
publisher = "Springer Wien",
number = "1-2",

}

TY - JOUR

T1 - Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain

T2 - Challenging the gene dosage effect hypothesis (Part II)

AU - Cheon, M. S.

AU - Bajo, M.

AU - Kim, S. H.

AU - Claudio, J. O.

AU - Stewart, Alexander Keith

AU - Patterson, D.

AU - Kruger, W. D.

AU - Kondoh, H.

AU - Lubec, Gert

PY - 2003/3

Y1 - 2003/3

N2 - Down syndrome (DS) is the most common genetic cause of mental retardation. To explain the impact of extra chromosome 21 in the pathology of DS, gene dosage effect hypothesis has been proposed, but several investigators including our group have challenged this hypothesis. Although analysis of the sequence of chromosome 21 has been essentially completed, the molecular and biochemical mechanisms underlying the pathology are still unknown. We therefore investigated expression levels of six proteins encoded on chromosome 21 (HACS1, DYRK1A, αA-crystallin, FTCD, GARS-AIRS-GART, and CBS) in fetal cerebral cortex from DS and controls at 18-19 weeks of gestational age using Western blot analysis. Protein expression of HACS1 was significantly and remarkably decreased in DS, and the expression levels of five proteins were comparable between DS and controls suggesting that the gene dosage effect hypothesis is not sufficient to fully explain the DS phenotype. We are continuing to quantify proteins whose genes are encoded on chromosome 21 in order to provide a better understanding of the pathobiochemistry of DS at the protein level.

AB - Down syndrome (DS) is the most common genetic cause of mental retardation. To explain the impact of extra chromosome 21 in the pathology of DS, gene dosage effect hypothesis has been proposed, but several investigators including our group have challenged this hypothesis. Although analysis of the sequence of chromosome 21 has been essentially completed, the molecular and biochemical mechanisms underlying the pathology are still unknown. We therefore investigated expression levels of six proteins encoded on chromosome 21 (HACS1, DYRK1A, αA-crystallin, FTCD, GARS-AIRS-GART, and CBS) in fetal cerebral cortex from DS and controls at 18-19 weeks of gestational age using Western blot analysis. Protein expression of HACS1 was significantly and remarkably decreased in DS, and the expression levels of five proteins were comparable between DS and controls suggesting that the gene dosage effect hypothesis is not sufficient to fully explain the DS phenotype. We are continuing to quantify proteins whose genes are encoded on chromosome 21 in order to provide a better understanding of the pathobiochemistry of DS at the protein level.

KW - AlphaA-crystallin

KW - CBS

KW - Chromosome 21

KW - Down syndrome

KW - DYRK1A

KW - FTCD

KW - GARS-AIRS-GART

KW - HACS1

UR - http://www.scopus.com/inward/record.url?scp=0037355919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037355919&partnerID=8YFLogxK

M3 - Article

VL - 24

SP - 119

EP - 125

JO - Amino Acids

JF - Amino Acids

SN - 0939-4451

IS - 1-2

ER -