In largest comparison ever between human and mouse genomes, scientists spotlight parental competition

November 12, 2000

Do you love Mom or Dad's genes best? It depends, scientists say, on the gene. In the biggest comparison between human and mouse DNA sequence to date, researchers from Johns Hopkins and the Whitehead Institute examine how organisms play favorites between their parents' genes, a phenomenon known as imprinting.

For most genes, the human genome does not actively distinguish between the copy inherited from the mother and the one from the father. Imprinted genes, however, are especially 'marked' so that one parent's copy virtually shuts down in deference to the other. In theory, imprinting represents competition between Mom and Dad over your genes: Mom turns a certain gene on and Dad turns it off, or vice versa. Yet despite the recent discovery that entire genome regions can be imprinted, scientists understand relatively little about the marking process for imprinted genes.

In this month's issue of Genome Research, Andy Feinberg and colleagues compare a large imprinted region in the human genome with its counterpart in the mouse genome. Covering 1 million adjacent base pairs, the comparison is the largest between humans and their mammalian relatives to date. The experiment successfully revealed all genes in the region and, more importantly, identified 82 non-gene DNA sequences that are similar between mouse and human. These segments are likely to be crucial genetic elements that control gene activity and constitute imprinting marks for this region. As discussed by Feinberg and colleagues, these results provide the first global view of an entire imprinted region in any genome.

In a related Genome Research study, Randy Jirtle and colleagues from Duke University have discovered a new pair of imprinted genes on human chromosome 14, called DLK1 and GTL2. These neighboring genes are "reciprocally" imprinted - that is, they interact so that you activate only your father's copy of DLK1 and only your mother's copy of GTL2. The structure and arrangement of this two-gene cluster is astonishingly similar to a similar cluster on chromosome 11, IGF2/H19, lately prominent in scientific news. The discovery indicates a common mechanism for reciprocal imprinting that may be used throughout the genome and across mammalian species.

Finally, in this issue, a commentary by Andy Hoffman and Thanh Vu from Stanford University discusses the importance of the Feinberg and Jirtle studies to the field of imprinting research.
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Articles and author contacts:

1) Sequence and Comparative Analysis of the Mouse 1-Megabase Region Orthologous to the Human 11p15 Imprinted Domain

Andy Feinberg
Institute of Genetic Medicine
Johns Hopkins University School of Medicine
Baltimore, MD 21205
USA
Email: afeinberg@jhu.edu

2) Novel Imprinted DLK1/GTL2 Domain on Human Chromosome 14 contains motifs that Mimic Those Implicated in IGF2/H19 Regulation

Randy Jirtle
Duke University Medical Center
Durham, NC 27710
USA
Email: jirtle@radonc.duke.edu

3) Comparative Genomics Sheds light on Mechanisms of Genomic Imprinting (Commentary)

Andy Hoffman
Department of Medicine
Stanford University
Palo Alto, CA 94301
USA
Email: arhoffman@leland.stanford.edu

Journal Contact (for copies of manuscripts):

Peggy Calicchia
Editorial Secretary
Genome Research
Email: calicchi@cshl.org
Phone: 1-516-367-6834

Cold Spring Harbor Laboratory

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