GeneWanderer

Category Genomics>Genetic Data Analysis/Tools

Abstract GeneWanderer is a web-based program that offers support for positional cloning projects by producing prioritized (ranked) lists of genes for sequencing.

Positional cloning projects often make use of linkage analysis to identify a chromosomal region in which a disease gene is located.

However, these regions, often referred to as 'linkage intervals', may contain up to several hundred genes and it is Not always apparent which of the genes is most likely to be the sought-after disease gene.

GeneWanderer combines two (2) sources of information in order to make its predictions.

First, a list of genes that are mutated in clinically similar disorders is required. For instance, there are many genetically heterogeneous disorders in which a mutation in one of multiple genes leads to a clinical similar or identical phenotype.

The manufacturer refers to such groups of disorders as disease-gene families. Two (2) well known examples are Retinitis Pigmentosa and Bardet-Biedl Syndrome.

Additionally, groups of genes involved in complex (polygenic) disorders or cancer syndromes may be used.

GeneWanderer can be used with one of 110 pre-defined disease-gene families or users can enter a list of Entrez Gene Ids in order to define their own disease-gene families.

The second piece of information required by GeneWanderer is the chromosomal location (linkage interval) in which the disease gene is located. Users are required to select a chromosome and enter the start and end position of the interval.

GeneWanderer then compares the locations of the known members of the disease-gene families within the protein-protein interaction (PPI) network to the positions of all the candidates in the linkage interval. It prioritizes the candidate genes based on proximity to the known disease-gene family members.

The calculated proximity depends on the procedures used to measure "closeness" in the network. As described in the manuscript “Walking the interactome for prioritizing candidate disease genes”, two (2) global network algorithms showed superior performance (Random Walk with Restart and the Diffusion Kernel).

The manufacturer also provides screens for direct interactions and shortest path to disease-gene family members for comparison purposes, but does Not recommend their use for new positional cloning projects.

You can learn more about this product from the following paper:

Walking the interactome for prioritization of candidate disease genes -- AM J HUM Genet. 2008 Apr; 82(4):949-58. Epub 2008 Mar 27.

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G6G Abstract Number 20208

G6G Manufacturer Number 100505