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Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster

Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster
Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster
Using a combination of multiplex amplifiable probe hybridization and semiquantitative fluorescence in situ hybridization (SQ-FISH), we analyzed DNA copy number variation across chromosome band 8p23.1, a region that is frequently involved in chromosomal rearrangements. We show that a cluster of at least three antimicrobial beta-defensin genes (DEFB4, DEFB103, and DEFB104) at 8p23.1 are polymorphic in copy number, with a repeat unit >/=240 kb long. Individuals have 2-12 copies of this repeat per diploid genome. By segregation, microsatellite dosage, and SQ-FISH chromosomal signal intensity ratio analyses, we deduce that individual chromosomes can have one to eight copies of this repeat unit. Chromosomes with seven or eight copies of this repeat unit are identifiable by cytogenetic analysis as a previously described 8p23.1 euchromatic variant. Analysis of RNA from different individuals by semiquantitative reverse-transcriptase polymerase chain reaction shows a significant correlation between genomic copy number of DEFB4 and levels of its messenger RNA (mRNA) transcript. The peptides encoded by these genes are potent antimicrobial agents, especially effective against clinically important pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, and DEFB4 has been shown to act as a cytokine linking the innate and adaptive immune responses. Therefore, a copy number polymorphism involving these genes, which is reflected in mRNA expression levels, is likely to have important consequences for immune system function.
0002-9297
591-600
Hollox, E.J.
9a1d99f2-06bd-485c-bbe7-9ed12a872c31
Armour, J.A.
11ae30b7-4758-4f72-88a4-6df500076eb2
Barber, J.C.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Hollox, E.J.
9a1d99f2-06bd-485c-bbe7-9ed12a872c31
Armour, J.A.
11ae30b7-4758-4f72-88a4-6df500076eb2
Barber, J.C.
4785a6e4-bd63-4230-ab61-41a0ae12c761

Hollox, E.J., Armour, J.A. and Barber, J.C. (2003) Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster. American Journal of Human Genetics, 73 (3), 591-600. (doi:10.1086/378157).

Record type: Article

Abstract

Using a combination of multiplex amplifiable probe hybridization and semiquantitative fluorescence in situ hybridization (SQ-FISH), we analyzed DNA copy number variation across chromosome band 8p23.1, a region that is frequently involved in chromosomal rearrangements. We show that a cluster of at least three antimicrobial beta-defensin genes (DEFB4, DEFB103, and DEFB104) at 8p23.1 are polymorphic in copy number, with a repeat unit >/=240 kb long. Individuals have 2-12 copies of this repeat per diploid genome. By segregation, microsatellite dosage, and SQ-FISH chromosomal signal intensity ratio analyses, we deduce that individual chromosomes can have one to eight copies of this repeat unit. Chromosomes with seven or eight copies of this repeat unit are identifiable by cytogenetic analysis as a previously described 8p23.1 euchromatic variant. Analysis of RNA from different individuals by semiquantitative reverse-transcriptase polymerase chain reaction shows a significant correlation between genomic copy number of DEFB4 and levels of its messenger RNA (mRNA) transcript. The peptides encoded by these genes are potent antimicrobial agents, especially effective against clinically important pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, and DEFB4 has been shown to act as a cytokine linking the innate and adaptive immune responses. Therefore, a copy number polymorphism involving these genes, which is reflected in mRNA expression levels, is likely to have important consequences for immune system function.

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Published date: 1 September 2003
Organisations: Medicine

Identifiers

Local EPrints ID: 40725
URI: http://eprints.soton.ac.uk/id/eprint/40725
ISSN: 0002-9297
PURE UUID: 4209e69e-717b-4aae-9fed-f7bbc530548c

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Date deposited: 07 Jul 2006
Last modified: 15 Mar 2024 08:21

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Contributors

Author: E.J. Hollox
Author: J.A. Armour
Author: J.C. Barber

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