Dr Cushla McKinney

Research Fellow
CushlaMcKinney3
  • Biochemistry Department
  • School of Biomedical Sciences
  • University of Otago
  • P.O. Box 56
  • 710 Cumberland St
  • Dunedin 9054 , New Zealand
  • Tel.: 64 3 479-3425
  • Fax: 64 3 479-7866
  • Email:cushla.mckinney@otago.ac.nz

Dr McKinney has a PhD in Biochemistry and a Masters in Bioethics and Health Law, both from the University of Otago. For the past few years she has been researching the genetics of autoimmune disease, focusing on the role of copy number variation on susceptibility to rheumatoid arthritis. Her latest project is intended to identify immune-system genes involved in the development of gout, a serious and debilitating form of inflammatory arthritis that is especially prevalent among Maori and Pacific Island New Zealanders.

Research Interests:

Copy Number Variation and Autoimmune Disease

Until relatively recently, single nucleotide polymorphisms (SNPs) were considered to be the major source of genetic variation in humans (and other animals). With the advent of whole‐genome sequencing and DNA microarray technology, it is now known that duplications and deletions of entire genes and gene regions are another common source of genetic variation. The first papers reporting large-scale copy number variation (CNV) were published in 2005, and since then an increasing number of studies showing association between CNV and disease susceptibility have been published. Dr McKinney’s work has focussed on CNV in two immune-system genes, the pro-inflammatory chemokine CCL3L1 and the leukocyte receptor FcgR3B, both of which influence susceptibility to rheumatoid arthritis in several different Caucasian populations.

Gout

Gout is caused by the build-up of uric acid crystals in the joints, leading to inflammation, swelling and extreme pain. In severe cases, it can result in permanent disability. The initial stage of disease is the development of hyperuricaemia, a build up of uric acid in the blood to the level that it crystalises.  This can occur because of high intake of foods that contain the precursors of uric acid (foods rich in purines such as red meat, and alcohol), and/or because the kidneys are unable remove it from the body efficiently.  Gout results when the immune system reacts against the urate crystals, causing inflammation and tissue destruction. Only 10-20% of those with hyperuricaemia go on to develop gout, however, suggesting that some people are more sensitive to uric acid than others.  I am currently working on identifying variations within genes of the immune system that differ significantly in frequency between gout patients and asymptomatic hyperuricaemic controls in Maori, Pacific Island and Caucasian New Zealanders.
This research is being carried out in collaboration with Associate Professor Tony Merriman,

Funding:

Arthritis New Zealand
Lotteries Health

Selected Publications:  

Phipps-Green P, McKinney C, Rossol M, Merriman ME, Topless R, Hollis-Moffatt JE, Wan Taib WJ, Dalbeth N, Gow PJ, Harrison AA, Highton J, Jones PBB, Lisa Stamp LK, Wanger U, Wordsworth P, Merriman TR. (2011) Analysis of association of DNASE2 promotor variation with rheumatoid arthritis in European Caucasians. Ann Rheum Dis 70(9):1512-1514.

McKinney C, Fanciulli M, Merriman ME, Phipps-Green A, Alizadeh BZ, Koeleman BP, Dalbeth N, Gow PJ, Harrison AA, Highton J, Jones PB, Stamp LK, Steer S, Barrera P, Coenen MJ, Franke B, van Riel PL, Vyse TJ, Aitman TJ, Radstake TR, Merriman TR. (2010) Association of variation in Fc {gamma}receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples. Ann Rheum Dis 69(9):1711-1716.

McKinney C, Merriman ME, Chapman PT, Gow PJ, Harrison AA, Highton J, Jones PB, McLean L, O'Donnell JL, Pokorny V, Spellerberg M, Stamp LK, Willis J, Steer S, Merriman TR. (2008) Evidence for an influence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis. Ann Rheum Dis. 67(3):109-13.

McKinney C and Merriman TR. (2007) The human genome and understanding of common disease:present and future technologies. Cell. Mol. Life Sci. 64:961-78.

Gil M, McKinney C, Lee MK, Eells JB, Phyillaier MA, Nikodem VM.  (2007) Regulation of GTP cyclohydrolase I expression by orphan receptor Nurr1 in cell culture and in vivo. J Neurochem101(1):142-50.

Selected Publications

Humaira Rasheed, Cushla Mckinney, Lisa K Stamp, Nicola Dalbeth, Ruth K Topless, Richard Day, Diluk Kannangara, Kenneth Williams, Malcolm Smith, Matthijs Janssen, Tim L Jansen, Leo A Joosten, Timothy R Radstake, Philip L Riches, Anne-Kathrin Tausche, Frédéric Lioté, Leo Lu, Eli A Stahl, Hyon K Choi, Alexander So, and Tony R Merriman., The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets., PLoS ONE 2016 vol. 11 (1) p. e0147939., Link »

Cushla Mckinney, Lisa K Stamp, Nicola Dalbeth, Ruth K Topless, Richard O Day, Diluk Rw Kannangara, Kenneth M Williams, Matthijs Janssen, Timothy L Jansen, Leo A Joosten, Timothy R Radstake, Philip L Riches, Anne-Kathrin Tausche, Frédéric Lioté, Alexander So, and Tony R Merriman., Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout., Arthritis Res Ther 2015 vol. 17 (1) p. 288., Link »

Suneeth F Mathew, Caillan Crowe-McAuliffe, Ryan Graves, Tony S Cardno, Cushla Mckinney, Elizabeth S Poole, and Warren P Tate., The Highly Conserved Codon following the Slippery Sequence Supports -1 Frameshift Efficiency at the HIV-1 Frameshift Site., PLoS ONE 2015 vol. 10 (3) p. e0122176., Link »

C Mckinney, J C A Broen, M C Vonk, L Beretta, R Hesselstrand, N Hunzelmann, G Riemekasten, R Scorza, C P Simeon, V Fonollosa, P E Carreira, N Ortego-Centeno, M A Gonzalez-Gay, P Airo, M Coenen, J Martín, T R D J Radstake, and T R Merriman, Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis., Genes and Immunity 13, 458-460, Link »

Cushla Mckinney and Tony R Merriman, Meta-analysis confirms a role for deletion in FCGR3B in autoimmune phenotypes., Human Molecular Genetics (2012), Link »

M Chen-Xu, R Topless, C Mckinney, M E Merriman, A Phipps-Green, N Dalbeth, P J Gow, A A Harrison, J Highton, P B Jones, M Nissen, M D Smith, A Van Rij, G T Jones, L Rodriguez-Rodriguez, B Fernandez-Gutierrez, M Teruel, A Balsa, D Pascual-Salcedo, A M Ortiz, M A Gonzalez-Gay, S Steer, M Maehlen, B Lie, B P Wordsworth, L K Stamp, J Martín, and T R Merriman, Replication of association of the interleukin 23 receptor rs1343151 variant with rheumatoid arthritis in Caucasian sample sets, Annals of the Rheumatic Diseases 2012 vol. 71 (1) pp. 155-157, Link »