Human artificial chromosome

A human artificial chromosome (HAC) is a microchromosome that can act as a new chromosome in a population of human cells. That is, instead of 46 chromosomes, the cell could have 47 with the 47th being very small, roughly 6–10 megabases (Mb) in size instead of 50–250 Mb for natural chromosomes, and able to carry new genes introduced by human researchers. Ideally, researchers could integrate different genes that perform a variety of functions, including disease defense. Alternative methods of creating transgenes, such as utilizing yeast artificial chromosomes and bacterial artificial chromosomes, lead to unpredictable problems. The genetic material introduced by these vectors not only leads to different expression levels, but the inserts also disrupt the original genome. HACs differ in this regard, as they are entirely separate chromosomes. This separation from existing genetic material assumes that no insertional mutants would arise. This stability and accuracy makes HACs preferable to other methods such as viral vectors, YACs, and BACs. HACs allow for delivery of more DNA (including promoters and copy-number variation) than is possible with viral vectors. Yeast artificial chromosomes and bacterial artificial chromosomes were created before human artificial chromosomes, which were first developed in 1997. HACs are useful in expression studies as gene transfer vectors, as a tool for elucidating human chromosome function, and as a method for actively annotating the human genome. HACs were first constructed de novo in 1997 by adding alpha-satellite DNA to telomeric and genomic DNA in human HT1080 cells. This resulted in an entirely new microchromosome that contained DNA of interest, as well as elements allowing it to be structurally and mitotically stable, such as telomeric and centromeric sequences. Due to the difficulty of de novo HAC formation, this method has largely been abandoned. There are currently two accepted models for the creation of human artificial chromosome vectors.