Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation in an Indian family presenting with an autosomal recessive neurological disorder

Abstract

The use of genome wide genotyping arrays has the potential to assess entire groups of genetic disorders in one application and has begun to emerge as an aid to diagnosis in clinical practice. Recessive families may suffer from diseases because of homozygosity of recessive alleles; homozygosity tracks can be easily identified by using these high throughput SNPs arrays, allowing the rapid mapping of autozygous segments that may be associated with the disease. According to this, we performed homozygosity mapping using genome wide SNP arrays in a North Indian family with an autosomal recessive disorder of ataxia, epilepsy, cognitive decline and visual problems. In this kindred, a large number of homozygous regions were identified. In silico analysis was also carried out. The COL18A1 gene found in one of the homozygous tracks has genetic defects previously reported with a similar phenotype as our family. Hence, it was the most likely candidate gene and at large the first to be analyzed. A homozygous COL18A1 two base pair deletio segregating with the disease was identified; expanding the spectrum of disease seen in COL18A1 and proving that the genetic lesion underlying recessive disorders can rapidly identify by employing genotyping arrays along with detailed candidate gene analysis.