Identification of candidate disease genes by EST alignments, synteny, and expression and verification of Ensembl genes on rat chromosome 1q43-54 - PubMed (original) (raw)

Comparative Study

doi: 10.1101/gr.1932304.

Darryl Gietzen, Kristian Stevens, Jim Wingrove, Shanya Becha, Sean Bulloch, John Burrill, Narinder Chawla, Jennifer Chien, Matthew Crawford, Craig Ison, Liam Kearney, Mary Kwong, Joe Park, Jennifer Policky, Mark Weiler, Renee White, Yuming Xu, Sue Daniels, Howard Jacob, Michael I Jensen-Seaman, Jozef Lazar, Laura Stuve, Jeanette Schmidt

Affiliations

Comparative Study

Identification of candidate disease genes by EST alignments, synteny, and expression and verification of Ensembl genes on rat chromosome 1q43-54

Ursula Vitt et al. Genome Res. 2004 Apr.

Abstract

We aligned Incyte ESTs and publicly available sequences to the rat genome and analyzed rat chromosome 1q43-54, a region in which several quantitative trait loci (QTLs) have been identified, including renal disease, diabetes, hypertension, body weight, and encephalomyelitis. Within this region, which contains 255 Ensembl gene predictions, the aligned sequences clustered into 568 Incyte genes and gene fragments. Of the Incyte genes, 261 (46%) overlapped 184 (72%) of the Ensembl gene predictions, whereas 307 were unique to Incyte. The rat-to-human syntenic map displays rearrangement of this region on rat chr. 1 onto human chromosomes 9 and 10. The mapping of corresponding human disease phenotypes to either one of these chromosomes has allowed us to focus in on genes associated with disease phenotypes. As an example, we have used the syntenic information for the rat Rf-1 disease region and the orthologous human ESRD disease region to reduce the size of the original rat QTL to only 11.5 Mb. Using the syntenic information in combination with expression data from ESTs and microarrays, we have selected a set of 66 candidate disease genes for Rf-1. The combination of the results from these different analyses represents a powerful approach for narrowing the number of genes that could play a role in the development of complex diseases.

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Figures

Figure 1

Figure 1

Overlap between the Ensembl and Incyte gene data set.

Figure 2

Figure 2

Browser shot of Incyte and Ensembl genes in a subregion of chr. 1q43-54. Incyte genes IDs are given in bold and are presented as green boxes, whereas the Ensembl genes are represented as brown boxes with the distinct nuremical part of the Ensembl gene ID (all have prefix of ENSRNOG000000*) below the boxes. Incyte transcripts are presented in blue. The number of Incyte ESTs (Incyte) and ESTs from the public domain (PD) are given below each gene ID. Protein sequence start and stop locations are indicated by arrows in the transcripts. (*) Genes composed of Incyte ESTs only.

Figure 3

Figure 3

Syntenic map for rat chr. 1q43-54. Markers associated with _Rf_-,Niddm24, Bp42, Weight3, and Eae7 (D1Mit8, D1Mit18, D1mit34, D1Rat156, and D1Mgh12) and for human ESRD (D10S677), are presented as bold yellow lines. Some of the known gene symbols were added for orientation. Syntenic segments that changed orientation on human chromosomes are linked by broken lines to rat chr1.

Figure 4

Figure 4

GO terms predicted for candidate genes for Rf-1. (Top) GO terms for biological processess. (Bottom) GO terms for molecular function.

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WEB SITE REFERENCES

    1. http://ratmap.gen.gu.se/; The rat genome database.
    1. http://www.ncbi.nlm.nih.gov/genome/sts/; UniSTS:
    1. http://www.ncbi.nlm.nih.gov/geo/; GEO
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