Human Genetics

, Volume 133, Issue 10, pp 1217–1233 | Cite as

Human gene copy number variation and infectious disease

  • Edward J. Hollox
  • Boon-Peng Hoh
Review Paper


Variability in the susceptibility to infectious disease and its clinical manifestation can be determined by variation in the environment and by genetic variation in the pathogen and the host. Despite several successes based on candidate gene studies, defining the host variation affecting infectious disease has not been as successful as for other multifactorial diseases. Both single nucleotide variation and copy number variation (CNV) of the host contribute to the host’s susceptibility to infectious disease. In this review we focus on CNV, particularly on complex multiallelic CNV that is often not well characterised either directly by hybridisation methods or indirectly by analysis of genotypes and flanking single nucleotide variants. We summarise the well-known examples, such as α-globin deletion and susceptibility to severe malaria, as well as more recent controversies, such as the extensive CNV of the chemokine gene CCL3L1 and HIV infection. We discuss the potential biological mechanisms that could underly any genetic association and reflect on the extensive complexity and functional variation generated by a combination of CNV and sequence variation, as illustrated by the Fc gamma receptor genes FCGR3A, FCGR3B and FCGR2C. We also highlight some understudied areas that might prove fruitful areas for further research.


Copy Number Variation Segmental Duplication Human African Trypanosomiasis Copy Number Allele Paralogue Ratio Test 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



B.P.H. thanks the Ministry of Long Term Research Grant Scheme (LRGS) for Infectious Disease, 2011-14, Ministry of Higher Education, Malaysia [600-RMI/LRGS 5/3 (3/2011)]. E.J.H. thanks colleagues for support, and Razan Abujaber and Ezgi Kucikkilic for comments on the manuscript.


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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of GeneticsUniversity of LeicesterLeicesterUK
  2. 2.Faculty of Medicine, Institute of Medical Molecular BiotechnologyUniversiti Teknologi MARA, Sungai Buloh Campus, Jalan HospitalSungai BulohMalaysia

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