Skip to main content

Research Repository

Advanced Search

Accurate measurement of gene copy number for human alpha-defensin DEFA1A3

Khan, Fayeza F.; Carpenter, Danielle; Mitchell, Laura; Mansouri, Omniah; Black, Holly A.; Tyson, Jess; Armour, John A.L.

Accurate measurement of gene copy number for human alpha-defensin DEFA1A3 Thumbnail


Authors

Fayeza F. Khan

Danielle Carpenter

Laura Mitchell

Omniah Mansouri

Holly A. Black

Jess Tyson

John A.L. Armour



Abstract

Background:
Multi-allelic copy number variants include examples of extensive variation between individuals in the copy number of important genes, most notably genes involved in immune function. The definition of this variation, and analysis of its impact on function, has been hampered by the technical difficulty of large-scale but accurate typing of genomic copy number. The copy-variable alpha-defensin locus DEFA1A3 on human chromosome 8 commonly varies between 4 and 10 copies per diploid genome, and presents considerable challenges for accurate high-throughput typing.

Results:
In this study, we developed two paralogue ratio tests and three allelic ratio measurements that, in combination, provide an accurate and scalable method for measurement of DEFA1A3 gene number. We combined information from different measurements in a maximum-likelihood framework which suggests that most samples can be assigned to an integer copy number with high confidence, and applied it to typing 589 unrelated European DNA samples. Typing the members of three-generation pedigrees provided further reassurance that correct integer copy numbers had been assigned. Our results have allowed us to discover that the SNP rs4300027 is strongly associated with DEFA1A3 gene copy number in European samples.

Conclusions:
We have developed an accurate and robust method for measurement of DEFA1A3 copy number. Interrogation of rs4300027 and associated SNPs in Genome-Wide Association Study SNP data provides no evidence that alpha-defensin copy number is a strong risk factor for phenotypes such as Crohn’s disease, type I diabetes, HIV progression and multiple sclerosis.

Citation

Khan, F. F., Carpenter, D., Mitchell, L., Mansouri, O., Black, H. A., Tyson, J., & Armour, J. A. (2013). Accurate measurement of gene copy number for human alpha-defensin DEFA1A3. BMC Genomics, 14(719), https://doi.org/10.1186/1471-2164-14-719

Journal Article Type Article
Publication Date Oct 20, 2013
Deposit Date Mar 28, 2014
Publicly Available Date Mar 28, 2024
Journal BMC Genomics
Electronic ISSN 1471-2164
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 14
Issue 719
DOI https://doi.org/10.1186/1471-2164-14-719
Public URL https://nottingham-repository.worktribe.com/output/718586
Publisher URL http://www.biomedcentral.com/1471-2164/14/719

Files





You might also like



Downloadable Citations