# MOLECULAR GENETICS OF DOWN SYNDROME

> **NIH NIH R01** · STANFORD UNIVERSITY · 1994 · $180,690

## Abstract

The overall objective of this project is to learn more about the
mechanisms by which trisomy for human chromosome 21 interferes with
normal development and function to result in the neurologic abnormalities
commonly observed in Down syndrome.  Over the past five years, we have
constructed physical maps of human chromosome 21 which have been used in
conjunction with patients who have imbalance for different portions of
chromosome 21 to demonstrate that imbalance of a 10 megabase "critical
region" of the long arm of chromosome 21 results in more severe
neurologic abnormalities than imbalance of other segments of he
chromosome.  We now propose to develop a comprehensive approach for
identifying genes encoded by this 10 megabase region of chromosome 21,
and to determine which genes encoded by this region are most likely to
result in neurologic abnormalities when present in three rather than two
copies.  Initially, we will focus our attention on the 2 Mb portion of
the 10 Mb critical region of chromosome 21 that contains the EPM1 gene.
This gene, when mutated, results in an autosomal recessive form of
progressive myoclonous epilepsy.  As part of a systematic analysis of
chromosome 21 transcripts from this region, we propose to isolate the
EPM1 gene by "positional cloning".  Since mutation of EPM1 is known to
result in adverse neurologic consequences.  Thus, we particularly
interested in isolating this gene, gaining insight into its function
through sequence analysis, and studying its expression in trisomy 21
versus diploid cells.  In addition to isolation and characterization of
EPM1, we will study the transcriptional pattern in trisomy 21 versus
normal diploid cells for each of the estimated 300 genes that we propose
to isolate from the 10 Mb critical region of the chromosome.  A primary
goal of this proposal is to determine what fraction of chromosome 21
genes demonstrate dramatic increases or decreases in gene expression at
the transcriptional level when present in genes through a comparison of
their sequences with those of known genes.

## Key facts

- **NIH application ID:** 2199242
- **Project number:** 2R01HD024610-07
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** DAVID R COX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $180,690
- **Award type:** 2
- **Project period:** 1988-08-01 → 1997-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199242

## Citation

> US National Institutes of Health, RePORTER application 2199242, MOLECULAR GENETICS OF DOWN SYNDROME (2R01HD024610-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199242. Licensed CC0.

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