Single Nucleotide Polymorphisms (SNPs) are very common mutation in the genome.
They correspond to a change from an A,C,G,T base into another one.

They can be used in many different ways to identify various property of the Genome:
  • Linkage
  • Association
  • Loss of Heterozygosity
  • Genomic Copy Number Variation

Association Studies

Markers have long been used to perform association studies where the goal is to link a phenotype (affected patient, BMI, BMD, etc.) to a specific genotype.
Tradionally used as the final point of positional cloning, it is now possible to test hundreds of thousands of SNPs Genome-Wide.

Recently we have been involved in the Genome-Wide Association of Colorectal Cancer with the CORGI consortium led by Prof. Ian Tomlinson and Richard Houlston:

Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W, Barclay E, Lubbe S, Martin L, Sellick G, Jaeger E, Hubner R, Wild R, Rowan A, Fielding S, Howarth K; CORGI Consortium, Silver A, Atkin W, Muir K, Logan R, Kerr D, Johnstone E, Sieber O, Gray R, Thomas H, Peto J, Cazier JB, Houlston R.
Nature genetics (2007) 08;39:984-8

Peter Broderick, Luis Carvajal-Carmona, Alan M Pittman, Emily Webb, Kimberley Howarth, Andrew Rowan, Steven Lubbe, Sarah Spain, Kate Sullivan, Sarah Fielding, Emma Jaeger, Jayaram Vijayakrishnan, Zoe Kemp, Maggie Gorman, Ian Chandler, Elli Papaemmanuil, Steven Penegar, Wendy Wood, Gabrielle Sellick, Mobshra Qureshi, Ana Teixeira, Enric Domingo, Ella Barclay, Lynn Martin, Oliver Sieber, David Kerr, Richard Gray, Julian Peto, Jean-Baptiste Cazier, Ian Tomlinson, Richard S Houlston Nature Genetics 39, 1315 - 1317 (14 Oct 2007)

Emma Jaeger, Emily Webb, Kimberley Howarth, Luis Carvajal-Carmona, Andrew Rowan, Peter Broderick, Axel Walther, Sarah Spain, Alan Pittman, Zoe Kemp, Kate Sullivan, Karl Heinimann, Steven Lubbe, Enric Domingo, Ella Barclay, Lynn Martin, Maggie Gorman, Ian Chandler, Jayaram Vijayakrishnan, Wendy Wood, Elli Papaemmanuil, Steven Penegar, Mobshra Qureshi, members of the CORGI Consortium, Susan Farrington, Albert Tenesa, Jean-Baptiste Cazier, David Kerr, Richard Gray, Julian Peto, Malcolm Dunlop, Harry Campbell, Huw Thomas, Richard Houlston & Ian Tomlinson
Nature Genetics 40, 26 - 28 (2007)

Houlston, Cazier et al.
Nature Genetics (2008) 02;In Press

Loss of Heterozygosity

SNP array provide genotype data across large regions. Markers are usually in Hardy-Weinberg equilibrium, and therefore we expect, by chance to have a certain proportion (2.frq.(1-frq)) of heterozygotes. However in case of chromosome loss, the heterozygotes will disappear resulting in an apparent Loss of Heterozygosity (LOH). Stretches of LOH often reveal local aberrations such as deletions or acquired UniParental Disomy (aUPD).


Copy Number Variation

The genotypes from SNParrays are actually derived from probe level signal intensities on chips. These signal intensities can be used to give a relative measure of genomic material present.
In fact it can easily be used to identify Copy Number changes in the genome.

Elodie E. Noel, Jackie Perry, Tracy Chaplin, Xueying Mao, Jean-Baptiste Cazier, Simon P. Joel, R. Tim D. Oliver, Bryan D. Young, and Yong-Jie Lu
Identification of Genomic Changes Associated with Cisplatin Resistance in Testicular Germ Cell Tumor Cell Lines.
Genes, Chromosomes and Cancer (2008) 02; In press