# GENES, ANEUPLOIDY, AND MAMMALIAN DEVELOPMENT

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 1994 · $1,285,129

## Abstract

An extra copy of chromosome 21(HSA21, trisomy 21) occurs frequently in
man (in 1/700-1/1000 births) and results in Down syndrome (DS); one of
the most common know causes of metal retardation.  The DS phenotype has
a wide array of major and minor abnormalities but all individuals do not
display all the of the array.  DS is characterized by specific features,
which, like the phenotypic consequences of other trisomies, make it
distinct, suggesting that there is a direct relationship between specific
genes that are at dosage imbalance and the resultant phenotype.  For
example, DS is characterized by dysmorphia features of the face and head,
congenital anomalies of the heart, immunodeficiency, mental retardation,
and dermatoglyphic changes.

Current research on DS focuses on the identification and molecular
analysis of genes on HSA 21, the characterization of the minimum region
of HSA 21 that is responsible for a subset of the major phenotypic
features of the syndrome, the molecular basis of chromosomal
nondisjunction, and the use of mouse models (either those that are
trisomic or partially trisomic for conserved regions of HSA21 on mouse
chromosomes (MMU) 16, 17, or 10, or mice produced through transgenic
technologies) to help elucidate the mechanisms by which extra copies of
chromosomal segments or genes exert their effects on phenotype.

Over the past five years, we have made significant research progress
towards a better understanding of DS biology through the use of
recombinant DNA technology in the analysis of HSA 21 and MMU16, the
development of reagents for the analysis of large, cloned DNA segments
as yeast artificial chromosomes (YACs), and the transfer of YACs into the
mouse germ line, generating mouse models for study.  In this competitive
renewal application, we propose experiments: 1) that will lead to a
better understanding of which genes, when present in triplicate, lead to
the DS phenotype, particularly with respect to the neurobiologic
consequences, through the use of segmental aneuploidy in the mouse and
transgenic ice carrying large segments of HSA21 cloned in YACs; 2) that
will improve methodologies for YAC cloning, manipulation, and transfer,
and 3) that will gain insights into the determinants important for
meiosis I chromosome disjunction.

## Key facts

- **NIH application ID:** 2199236
- **Project number:** 2P01HD024605-06
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** John D Gearhart
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $1,285,129
- **Award type:** 2
- **Project period:** 1989-04-01 → 1999-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199236

## Citation

> US National Institutes of Health, RePORTER application 2199236, GENES, ANEUPLOIDY, AND MAMMALIAN DEVELOPMENT (2P01HD024605-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199236. Licensed CC0.

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