Researchers identify gene required for marking DNA as having come from the mother

December 11, 2001

NEW YORK, - In a finding that could help scientists better understand the basis of sexual reproduction, researchers at Columbia University College of Physicians & Surgeons have for the first time identified a gene required for establishing the genomic imprinting of maternal genes.

Genomic imprinting is the process that marks parts of the genome, or the entire collection of genetic material of an organism, as having been inherited from one's mother or father.

Each cell in the human body has 23 pairs of chromosomes, with one of each pair coming from the mother and the other derived from the father. But besides inheriting the 30,000 to 50,000 genes carried by the 23 chromosomes, some 100 to 200 genes in humans carry an extra mark, or imprint, that identifies them as having come from either mom or dad.

The mark is usually in the form of the addition to the DNA of a chemical substance, called a methyl group. Methylation increases the information content of DNA and can be used to keep genes in the inactive state.

Scientists have known for some time that imprinting silences genes in offspring, allowing the other copy of the gene to be expressed. Researchers have reported a variety of genes--such as the one for Igf2 (insulin-like growth factor-2) and H19--that are expressed differently in offspring, depending on if they came from the mother or father. But almost nothing has been known about the genes that mark the DNA for imprinting during the formation of the sperm and egg.

In research published in the Nov. 23 issue of Science magazine's online publication Science Express, Columbia scientists have identified a gene, Dnmt3L, that is required for chemically marking certain parts of the mouse genome as being inherited from the mother. The gene is the first to be shown to play a role in the establishment of imprinting during egg development.

Led by Dr. Timothy Bestor, professor of genetics and development, the Columbia researchers genetically engineered mice that were missing the Dnmt3L gene. The offspring of female mice that lacked Dnmt3L expressed genes that are normally not expressed from the copy inherited from the mother.

The product of the Dnmt3L gene does not appear to actually add the methyl group to DNA, the researchers say, but is more likely to be a regulatory factor. They are now investigating its role in imprinting in mice and men and will soon seek other genes that are involved in the imprinting process.

Scientists believe imprinting may play a role in the prevention of uniparental or one-parent offspring in higher life forms. Although scientists can create embryos formed with either two paternal or two maternal genomes, such embryos cannot undergo further development. Apparently, the silencing of one of the pair of genes by imprinting plays an important function in the developing embryo.

Columbia University College of Physicians & Surgeons has a unique history in performing imprinting research.
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Columbia University Medical Center

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