Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News Archive Edition
Human Genome News, May 1993; 5(1)
Investigators at the Whitehead Institute for Biomedical Research have successfully introduced a yeast artificial chromosome (YAC) into the mouse genome and demonstrated that the chromosome and gene expression were transmitted in two "transgenic" mouse strains. This achievement was reported in the March 26 issue of Science (259, 1904-08).
A team headed by Rudolf Jaenisch, of the Whitehead genome center, inserted YAC DNA carrying a normal mouse collagen gene into embryonic stem (ES) cells derived from very early mouse embryos lacking a functional collagen gene. ES cells have the potential to develop into any type of cell in the body. Injecting the altered ES cells into intact host embryos produced chimeras (mixed animals), some of whose offspring carried functional YAC DNA in every cell.
The ability to transfer physically intact YACs into the germ line will permit the identification of regulatory sequences that control gene function. Many early gene-therapy experiments failed in mice because investigators could not control the level or timing of gene expression. With YAC technology, scientists can design a series of gene-transfer experiments to identify the combination of genetic elements most likely to produce acceptable levels of gene expression. Once the regulatory elements have been identified, human counterparts can be incorporated into vectors for human gene therapy.
YAC vectors have the advantage of being able to carry pieces of foreign DNA more than 20 times larger than those incorporated by conventional cloning vectors, which are limited to genes of less than 50 kb. This limitation impeded the development of accurate disease models because some human disease genes, such as those for neurofibromatosis, muscular dystrophy, and hemophilia, approach 100 kb.
The new YAC technology can also be used to pinpoint new disease genes whose approximate locations have been determined by gene mapping. Gene function and precise location can be studied in mice by inserting all or part of the gene-carrying DNA fragment and observing the results.
Jaenisch said that the ability to introduce YAC clones into the mouse germ line will allow quick and efficient application of new information from the Human Genome Project to the study of human disease.
Insertion of YACs has also been reported by Cell Genesys Inc. (Foster City, California) in the March 18 issue of Nature (362, 255-58) and by a group led by T. Choi (in press at Nature Genetics).
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Human Genome Program, U.S. Department of Energy, Human Genome News (v5n1).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.
Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.