Four years after the announcement of Dolly the cloned sheep, scientists struggle to produce healthy cloned animals. Cloning attempts often result in spontaneous abortions and animals that survive to birth are often born obese and develop heart abnormalities, lung defects and other problems. A new study from Yong-Mahn Han (of the Korea Research Institute of Bioscience and Biotechnology, Taejon, South Korea) indicates that the developmental abnormalities of cloned embryos may be due to defects in the genetic imprint of the donor DNA (Nature Genetics, Vol. 28, No. 2, 01 June 2001).
Genetic imprinting is a process in which genes from the mother and father are chemically marked, so as to balance the expression of the two sets of genes. Some genes carry a mark (a methylation) on the maternal copy that keeps it turned off, so only the paternal gene is expressed. Other genes have a mark on the paternal gene, leaving only the maternal gene expressed. When embryos develop normally, a genome-wide erasure of the marks occurs, starting very early in development.
Han and colleagues studied a specific region of the genome in cells from cloned bovine embryos, and compared its methylation status to that of normal embryos. Unexpectedly, the cells of the cloned blastocysts have genomic methylation patterns that resemble those of the donor cells, but also show wide variation. This indicates that the early genome-wide reprogramming-the erasure of the methylation-has gone awry.
Aberrations in imprinting are already known to result in some human disorders; for instance, the chromosomes of people affected with Beckwith-Wiedemann syndrome have physical characteristics similar to those seen in clones. So, despite recent advances, significant hurdles-such as overcoming deficiencies in genetic reprogramming-must be cleared before animals can be routinely cloned.
Dr. Yong-Mahn Han
Korea Research Institute of
Bioscience & Biotechnology
Yusong, Taejon, South Korea
Telephone: +82 42-860-4429
Fax: +82 42-860-4608
Dr. Tony Perry
Advanced Cell Technology
Worcester, Massachusetts, USA
Telephone: +1 (508) 756-1212
Fax: +1 (508) 756-4468
(C) Nature Genetics press release.
Message posted by: Trevor M. D'Souza