DOE Human Genome Program Contractor-Grantee Workshop VIII
February 27-March 2, 2000  Santa Fe, NM

51. Structural and Functional Analysis of a Conserved Imprinted Region of Human Chromosome 19q13.4 and Mouse Chromosome 7

Joomyeong Kim^1,2, Vladimir Noskov³, Xiaochen Lu^1,2, Anne Bergmann^1,2, Tiffany Warth², Paul Richardson¹, Vladimir Larionov³, Natasha Kouprina³, and Lisa Stubbs^1,2

¹DOE Joint Genome Institute, 2800 Mitchell Avenue, Walnut Creek, CA; ²Genome Division, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA; and ³National Institute of Environmental Health Sciences, Laboratory of Molecular Genetics, Research Triangle Park, NC

stubbs5@llnl.gov

Mouse genetics studies have long ago predicted that a genomically imprinted domain would be found near the centromere of mouse chromosome 7, a region with known syntenic homology to human chromosome 19q. Animals that inherit only maternal alleles of this region die as neonates, suggesting the presence of a gene or genes, expressed exclusively from the paternal chromosome, which is required for normal development. In earlier studies, we mapped a known paternally-expressed gene, PEG3, to human 19q13.4, and we reasoned that other imprinted genes would be found nearby in a clustered imprinted domain. We have used the emerging human sequence and data derived from related mouse clone contigs to identify new genes near PEG3, and have demonstrated that these novel genes are also imprinted in mice. These new genes are expressed highly in embryos; one represents a strong candidate for the paternally expressed, neonatal lethal factor predicted by mouse genetics. Our studies demonstrate that, despite many basic similarities, human and mouse regions surrounding PEG3 have undergone significant changes in gene content and organization. We will discuss the structure, expression and evolution of genes in this imprinted region, discuss the potential functions of each gene, and speculate on the possible implications of these findings for the genetics of chromosome 19-linked disorders in humans.