Gene expression analysis of cultured amniotic fluid cell with Down syndrome by DNA microarray.
Complete or partial triplication of human chromosome 21 results in Down syndrome (DS). To analyze differential gene expressions in amniotic fluid (AF) cells of DS, we used a DNA microarray system to analyze 102 genes, which included 24 genes on chromosome 21, 28 genes related to the function of brain and muscle, 36 genes related to apoptosis, 4 genes related to extracellular matrix, 8 genes related to other molecular function and 2 house-keeping genes. AF cells were collected from 12 pregnancies at 16-18 weeks of gestation in DS (n=6) and normal (n=6) subjects. Our DNA microarray experiments showed that the expressions of 11 genes were altered by at least 2-folds in DS, as follows. Ten genes, COL6A1, CASP5, AKT2, JUN, PYGM, BNIP1, OSF-2, PRSS7, COL3A1, and MBLL were down-regulated and GSTT1 was only up-regulated. The differential expressions of GSTT1 and COL3A1 were further confirmed by semi-quantitative RT-PCR for each sample. The gene dosage hypothesis on chromosome 21 may explain the neurological and other symptoms of DS. However, our results showed that only two genes (COL6A1 and PRSS7), among 24 genes on chromosome 21, were down-regulated in the AF cells of DS. Our data may provide the basis for a more systematic identification of biological markers of fetal DS, thus leading to an improved understanding of pathogenesis for fetal DS.
Chung
In-Hyuk
IH
Functional Genomics Lab, Bundang Campus, College of Medicine, Pochon CHA University, Sungnam, Korea.
Lee
Sook-Hwan
SH
Lee
Kyo-Won
KW
Park
Sang-hee
SH
Cha
Kwang-Yul
KY
Kim
Nam-Soon
NS
Yoo
Hyang-Sook
HS
Kim
Yong Sung
YS
Lee
Suman
S
D000649:Amniocentesis; D000653:Amniotic Fluid / Q000166:cytology* / Q000378:metabolism*; D017209:Apoptosis; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21; D024061:Collagen Type III / Q000096:biosynthesis; D018076:DNA, Complementary / Q000378:metabolism; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D018628:Gene Dosage; D015870:Gene Expression; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
C439971:COL3A1 protein, human; D024061:Collagen Type III; D018076:DNA, Complementary; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase
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