KinSNP software for homozygosity mapping of disease genes using SNP microarrays

El-Ad David Amir,Tal Nagar,Vered Chalifa-Caspi,Jony Sheynin,Ofer Bartal,Efrat Morad,Ruti Parvari

doi:10.1186/1479-7364-4-6-394

Abstract

Consanguineous families affected with a recessive genetic disease caused by homozygotisation of a mutation offer a unique advantage for positional cloning of rare diseases. Homozygosity mapping of patient genotypes is a powerful technique for the identification of the genomic locus harbouring the causing mutation. This strategy relies on the observation that in these patients a large region spanning the disease locus is also homozygous with high probability. The high marker density in single nucleotide polymorphism (SNP) arrays is extremely advantageous for homozygosity mapping.We present KinSNP, a user-friendly software tool for homozygosity mapping using SNP arrays. The software searches for stretches of SNPs which are homozygous to the same allele in all ascertained sick individuals. User-specified parameters control the number of allowed genotyping 'errors' within homozygous blocks. Candidate disease regions are then reported in a detailed, coloured Excel file, along with genotypes of family members and healthy controls. An interactive genome browser has been included which shows homozygous blocks, individual genotypes, genes and further annotations along the chromosomes, with zooming and scrolling capabilities. The software has been used to identify the location of a mutated gene causing insensitivity to pain in a large Bedouin family. KinSNP is freely available from http://bioinfo.bgu.ac.il/bsu/software/kinSNP.

Highlights

The availability of high-density mapping microarrays, bearing sufficient probes to analyse 10,000 – 1,000,000 single nucleotide polymorphisms (SNPs) in one assay, offers an efficient alternative to traditional, microsatellite-based, genome-wide linkage scans.[1]
We present KinSNP, a new software tool for homozygosity mapping in SNP arrays from consanguineous families, which provides additional capabilities compared with existing software while simplifying program usage
Unlike the two existing equivalent software tools, ExcludeAR and AutoSNPa, reported runs of shared homozygosity (ROSHs) are defined by customised criteria, which consider genotype call confidence and allow for

Summary

Introduction

The availability of high-density mapping microarrays, bearing sufficient probes to analyse 10,000 – 1,000,000 single nucleotide polymorphisms (SNPs) in one assay, offers an efficient alternative to traditional, microsatellite-based, genome-wide linkage scans.[1]. We present KinSNP, a user-friendly software tool for homozygosity mapping using SNP arrays.

Results

Conclusion