Bacterial artificial chromosome

A bacterial artificial chromosome (BAC) is a DNA construct, based on a functional fertility plasmid (or F-plasmid), used for
transforming and cloning in bacteria, usually E. coli.[1][2][3] F-plasmids play a crucial role because they contain partition genes
that promote the even distribution of plasmids after bacterial cell division. The bacterial artificial chromosome's usual insert size
is 150–350 kbp.[4] A similar cloning vector called a PAC has also been produced from the DNA of P1 bacteriophage.

BACs are often used to sequence the genome of organisms in genome projects, for example the Human Genome Project. A short
piece of the organism's DNA is amplified as an insert in BACs, and then sequenced. Finally, the sequenced parts are rearranged in
silico, resulting in the genomic sequence of the organism. BACs were replaced with faster and less laborious sequencing methods
like whole genome shotgun sequencing and now more recently next-gen sequencing.

Contents
Common gene components
Contribution to models of disease
Inherited disease
Infectious disease
See also
References
External links

Common gene components

repE
for plasmid replication and regulation of copy number.
parA and parB
for partitioning F plasmid DNA to daughter cells during division and ensures stable
maintenance of the BAC.
A selectable marker
for antibiotic resistance; some BACs also have lacZ at the cloning site for blue/white
selection.
T7 & Sp6
phage promoters for transcription of inserted genes.

Contribution to models of disease

Inherited disease
BACs are now being utilized to a greater extent in modelling genetic diseases, often alongside transgenic mice. BACs have been
useful in this field as complex genes may have several regulatory sequences upstream of the encoding sequence, including
various promoter sequences that will govern a gene's expression level. BACs have been used to some degree of success with mice
when studying neurological diseases such as Alzheimer's disease or as in the case of aneuploidy associated with Down syndrome.
There have also been instances when they have been used to study specific oncogenes associated with cancers. They are
transferred over to these genetic disease models by electroporation/transformation, transfection with a suitable virus or
microinjection. BACs can also be utilized to detect genes or large sequences of interest and then used to map them onto the
human chromosome using BAC arrays. BACs are preferred for these kind of genetic studies because they accommodate much
larger sequences without the risk of rearrangement, and are therefore more stable than other types of cloning vectors.

Infectious disease
The genomes of several large DNA viruses and RNA viruses have been cloned as BACs. These constructs are referred to as
"infectious clones", as transfection of the BAC construct into host cells is sufficient to initiate viral infection. The infectious
property of these BACs has made the study of many viruses such as the herpesviruses, poxviruses and coronaviruses more
accessible.[5][6][7] Molecular studies of these viruses can now be achieved using genetic approaches to mutate the BAC while it
resides in bacteria. Such genetic approaches rely on either linear or circular targeting vectors to carry out homologous
recombination.[8]

See also
Cosmid
End-sequence profiling
Fosmid
Human artificial chromosome
Yeast artificial chromosome

References
1. O'Connor M, Peifer M, Bender W (June 1989). "Construction of large DNA segments in Escherichia coli".
Science. 244 (4910): 1307–12. doi:10.1126/science.2660262 (https://doi.org/10.1126%2Fscience.2660262).
PMID 2660262 (https://www.ncbi.nlm.nih.gov/pubmed/2660262).
2. Shizuya H, Birren B, Kim UJ, Mancino V, Slepak T, Tachiiri Y, Simon M (September 1992). "Cloning and stable
maintenance of 300-kilobase-pair fragments of human DNA in Escherichia coli using an F-factor-based vector" (h
ttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC50007). Proceedings of the National Academy of Sciences of the
United States of America. 89 (18): 8794–7. doi:10.1073/pnas.89.18.8794 (https://doi.org/10.1073%2Fpnas.89.18.
8794). PMC 50007 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC50007). PMID 1528894 (https://www.ncbi.nlm.
nih.gov/pubmed/1528894).
3. Shizuya H, Kouros-Mehr H (March 2001). "The development and applications of the bacterial artificial
chromosome cloning system" (http://www.kjm.keio.ac.jp/past/50/1/26.pdf) (PDF). The Keio Journal of Medicine.
50 (1): 26–30. doi:10.2302/kjm.50.26 (https://doi.org/10.2302%2Fkjm.50.26). PMID 11296661 (https://www.ncbi.n
lm.nih.gov/pubmed/11296661).
4. Stone NE, Fan JB, Willour V, Pennacchio LA, Warrington JA, Hu A, de la Chapelle A, Lehesjoki AE, Cox DR,
Myers RM (March 1996). "Construction of a 750-kb bacterial clone contig and restriction map in the region of
human chromosome 21 containing the progressive myoclonus epilepsy gene". Genome Research. 6 (3): 218–25.
doi:10.1101/gr.6.3.218 (https://doi.org/10.1101%2Fgr.6.3.218). PMID 8963899 (https://www.ncbi.nlm.nih.gov/pub
med/8963899).
5. Almazán F, González JM, Pénzes Z, Izeta A, Calvo E, Plana-Durán J, Enjuanes L (May 2000). "Engineering the
largest RNA virus genome as an infectious bacterial artificial chromosome" (https://www.ncbi.nlm.nih.gov/pmc/arti
cles/PMC25860). Proceedings of the National Academy of Sciences of the United States of America. 97 (10):
5516–21. doi:10.1073/pnas.97.10.5516 (https://doi.org/10.1073%2Fpnas.97.10.5516). PMC 25860 (https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC25860). PMID 10805807 (https://www.ncbi.nlm.nih.gov/pubmed/10805807).
 6. Domi A, Moss B (September 2002). "Cloning the vaccinia virus genome as a bacterial artificial chromosome in
Escherichia coli and recovery of infectious virus in mammalian cells" (https://www.ncbi.nlm.nih.gov/pmc/articles/P
MC129459). Proceedings of the National Academy of Sciences of the United States of America. 99 (19): 12415–
20. doi:10.1073/pnas.192420599 (https://doi.org/10.1073%2Fpnas.192420599). PMC 129459 (https://www.ncbi.n
lm.nih.gov/pmc/articles/PMC129459). PMID 12196634 (https://www.ncbi.nlm.nih.gov/pubmed/12196634).
7. Messerle M, Crnkovic I, Hammerschmidt W, Ziegler H, Koszinowski UH (December 1997). "Cloning and
mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome" (https://www.ncbi.nlm.nih.
gov/pmc/articles/PMC25110). Proceedings of the National Academy of Sciences of the United States of America.
94 (26): 14759–63. doi:10.1073/pnas.94.26.14759 (https://doi.org/10.1073%2Fpnas.94.26.14759). PMC 25110
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC25110). PMID 9405686 (https://www.ncbi.nlm.nih.gov/pubmed/94
05686).
8. Feederle R, Bartlett EJ, Delecluse HJ (December 2010). "Epstein-Barr virus genetics: talking about the BAC
generation" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063228). Herpesviridae. 1 (1): 6. doi:10.1186/2042-
4280-1-6 (https://doi.org/10.1186%2F2042-4280-1-6). PMC 3063228 (https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3063228). PMID 21429237 (https://www.ncbi.nlm.nih.gov/pubmed/21429237).

External links
The Big Bad BAC: Bacterial Artificial Chromosomes (http://www.scq.ubc.ca/?p=266) — a review from the
Science Creative Quarterly
Empire Genomics (http://www.empiregenomics.com/products-and-services/bac-clones-and-fish-probes)
(company that sells BAC clones from genomic libraries)
Amplicon Express (https://web.archive.org/web/20110817032210/http://genomex.com/page.php?page=)
(company that makes custom BAC libraries)

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