International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

A17 An Approach to Identifying Novel Imprinted Genes in the Mouse

L. A. Underkoffler1, J. Morabito1, P. G. Matteson2 and R. J. Oakey1. Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104; 2HHMI, Princeton University, Princeton, NJ 08544

Imprinting refers to the unequal expression of the maternal and paternal alleles of a gene. Inappropriate expression of some imprinted genes as the result of incorrect dosage control results in lethality during development. To date, 12 imprinted regions have been defined in the mouse through genetic means. 9 of these regions have been shown to contain at least 30 genes whose expression is regulated in an imprinted manner. A strategy has been developed for the identification of novel imprinted genes in the mouse. Robertsonian and reciprocal translocation mice have been utilized to identify imprinted genes on mouse chromosome 7. Chromosome 7 has been selected because it contains defined imprinted regions containing known imprinted genes and has conserved linkage to human imprinted disease loci.

Specific intercrosses between Robertsonian or reciprocal translocated mice allows for the production of maternal and paternal uniparental disomic embryos. Imprinted genes are either over expressed or not expressed in these embryos, therefore, they have RNA representative of only one parent making it possible to identify monoallelic expression using comparative RNA analysis such as differential display and microarray technology. Imprinting candidates are being screened for further study with sequence analysis, RT-PCR, as well as an allele specific assays, such as single nucleotide primer extension. We have identified one known imprinted gene from this study and are currently analyzing novel candidates for authentic monoallelic expression. Identification and characterization of these genes will enhance our understanding of normal embryonic mammalian development.

 


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