Identification and quantification of disease-related gene clusters

MOTIVATION DNA microarray technology and the completion of human and mouse genome sequencing programs are now offering new avenues for the investigation of complex genetic diseases. In particular, this makes possible the study of the spatial distribution of disease-related genes within the genome. We report on the first systematic search for clustering of genes associated with a polygenic autoimmune disease. RESULTS Using a set of cDNA microarray chip experiments in two mouse models of rheumatoid arthritis, we have identified approximately 200 genes based on their expression in inflamed joints and mapped them into the genome. We compute the spatial autocorrelation function of the selected genes and find that they tend to cluster over scales of a few megabase pairs. We then identify significant gene clusters using a friends-of-friends algorithm. This approach should aid in discovering functionally related gene clusters in the mammalian genome.

[1]  P. Peebles,et al.  The Large-Scale Structure of the Universe , 1980 .

[2]  T. Glant,et al.  Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. , 1987, Arthritis and rheumatism.

[3]  Andreas Rytz,et al.  Microarray data analysis: a practical approach for selecting differentially expressed genes , 2001, Genome Biology.

[4]  JÖRg Retzlaff.  P. Coles, F. Lucchin: The Origin and Evolution of Cos‐mic Structure. John Wiley & Sons Ltd, England 1995, XIX + 449 Seiten, Preis: $24,95 , 1996 .

[5]  Marc Davis,et al.  A survey of galaxy redshifts. V. The two-point position and velocity correlations. , 1983 .

[6]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[7]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[8]  Alexander S. Szalay,et al.  Galaxy Clustering in Early Sloan Digital Sky Survey Redshift Data , 2002 .

[9]  E. Wakeland,et al.  The genetics of complex autoimmune diseases: non-MHC susceptibility genes , 2001, Nature Immunology.

[10]  Partha S. Vasisht.  Computational Analysis of Microarray Data , 2003 .

[11]  C I Amos,et al.  A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. , 2001, American journal of human genetics.

[12]  Peter Coles,et al.  The Origin and Evolution of Cosmic Structure , 1996 .

[13]  Philippa Marrack,et al.  Autoimmune disease: why and where it occurs , 2001, Nature Medicine.

[14]  M. Dallman,et al.  Immunisation against heterologous type II collagen induces arthritis in mice , 1980, Nature.

[15]  R. Sheth,et al.  A Random Walk through Models of Nonlinear Clustering , 2000, Annals of the New York Academy of Sciences.

[16]  et al,et al.  Galaxy Clustering in Early SDSS Redshift Data , 2001, astro-ph/0106476.

[17]  M. Flajnik,et al.  Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. , 2001, Immunity.

[18]  J. Trowsdale,et al.  Genetic and functional relationships between MHC and NK receptor genes. , 2001, Immunity.