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.[1] HACs differ in this regard, as they are entirely separate chromosomes. This separation from existing genetic material assumes that no insertional mutants would arise.[2] This stability and accuracy makes HACs preferable to other methods such as viral vectors, YACs, and BACs.[3] HACs allow for delivery of more DNA (including promoters and copy-number variation) than is possible with viral vectors.[4]

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.[5]

  1. ^ Katoh M, Ayabe F, Norikane S, Okada T, Masumoto H, Horike S, Shirayoshi Y, Oshimura M (August 2004). "Construction of a novel human artificial chromosome vector for gene delivery". Biochemical and Biophysical Research Communications. 321 (2): 280–90. doi:10.1016/j.bbrc.2004.06.145. PMID 15358173.
  2. ^ Grimes BR, Rhoades AA, Willard HF (June 2002). "Alpha-satellite DNA and vector composition influence rates of human artificial chromosome formation". Molecular Therapy. 5 (6): 798–805. doi:10.1006/mthe.2002.0612. PMID 12027565.
  3. ^ Mejía JE, Willmott A, Levy E, Earnshaw WC, Larin Z (August 2001). "Functional complementation of a genetic deficiency with human artificial chromosomes". American Journal of Human Genetics. 69 (2): 315–26. doi:10.1086/321977. PMC 1235305. PMID 11452360.
  4. ^ Kouprina N, Earnshaw WC, Masumoto H, Larionov V (April 2013). "A new generation of human artificial chromosomes for functional genomics and gene therapy". Cellular and Molecular Life Sciences. 70 (7): 1135–48. doi:10.1007/s00018-012-1113-3. PMC 3522797. PMID 22907415.
  5. ^ Basu J, Compitello G, Stromberg G, Willard HF, Van Bokkelen G (July 2005). "Efficient assembly of de novo human artificial chromosomes from large genomic loci". BMC Biotechnology. 5: 21. doi:10.1186/1472-6750-5-21. PMC 1182356. PMID 15998466.