The mental retardation, physical handicaps, and premature aging of Down syndrome (DS) are caused by a triplication of all or parts of human chromosome 21 (CH21). The clarity of this cytogenetic definition belies a complex pathophysiology impacted by an unknown number of genes. The ultimate goal of this proposal is to identify some of these genes and their targets. A novel approach to this problem is proposed, which uses previously generated transgenetic mice and embryonic stem cells containing large genomic regions of CH 21 that have been implicated in the DS phenotype and have been manipulated as yeast artificial chromosomes (YACs). The technique of differential display/reverse transcriptase polymerase chain reaction (DDRTPCR) will be used to detect differential mRNA accumulation from both genes located on the DS region YACs, and on mouse genes that respond to human YAC-encoded gene products. This technique provides a visual representation of differential gene expression, and allows the """"""""capture"""""""" aid molecular manipulation of the differences. A series of high-throughput assays are proposed to classify, authenticate, map, and identify resultant cDNAs.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD008100-03
Application #
2655096
Study Section
Genome Study Section (GNM)
Program Officer
Hanson, James W
Project Start
1998-02-01
Project End
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218