| Summary: | 碩士 === 國立臺灣大學 === 分子醫學研究所 === 94 === The gene expression of Down syndrome (DS) is the most dubitative culprit for the etiology of mental retardation and aneupliody in human. The extra copy of the proximal part of chromosome 21q22.1~21q22.3 appears to result in the phenotypic DS: mental retardation, characteristic facial features, hand anomalies, and congenital heart defects. However, the gene profile of chromosome 21 in DS is not clear. In this project, we use FISH (Fluorescence in situ hybridization ) and Microarray techniques, to interpret the spatiotemporal contous of gene expression on the DS chromosome 21 at the interphase of mitosis .
To analyze the patterns of gene expression from microarray, we apply the scoring systems including two-sample t- test, Welch’s test or Significance analysis of microarrays (SAM) test in the two-group comparative experiments according to the principle of data fusion in information retrieval to combine the multiple scoring systems. A rank/score function is used as a predictive variable for the effectiveness of combination to improve the identification of significant genes. In addition, we use Mathcad software system to analyze results from FISH performed on the DS cells/normal cells from amniotic fluid / blood.
The results from microarray showed that: 1. there is no difference in gene expression in term of gender whether the gene is derived from DS patient or healthy individual. 2. Out of 22572 genes, 29 were detected significantly different between DS and healthy people. Furthermore, 18 out of these 29 positive genes were found on the chromosome 21, and are thought to perform the functions of cellular communication, metabolism, and differentiation.
Using FISH to stain the chromosomes at interphase, we found that the spatiotemporal territory of each pair of gene on chromosome belonging to healthy people is not random disregarding which type of cells examined. Furthermore, we found that there is an extra spatiotemporal territory of genes on the DS chromosome 21. The length of this surplus territory is rather short and out of the normal range.
In conclusion, we think that the 18 different genes found on the DS chromosome 21 are located on the surplus short piece of territory , and these extra genes may result in the dosage effects which drive the functions of cellular communication, metabolism, and differentiation aberrant.
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