score alongside the overlaid blocks of homozygosity. By taking into consideration the population allele frequencies for all SNPs via autozygosity mapping, the results of homozygosity can be confirmed. Furthermore, if two suspicious regions appear as a result of homozygosity mapping, autozygosity mapping may be able to distinguish between the two (ex. If one block of homozygosity is a result of a very non-diverse region of the genome, the LOD score will be very low). Tools for Homozygosity Mapping HomSI: a homozygous stretch identifier from next-generation sequencing data A tool that identifies homozygous regions using deep sequence data. Genome-wide knockdown studies Genome-wide knockdown studies are an example of the reverse genetics made possible by the acquisition of whole genome sequences, and the advent of genomics and gene-silencing technologies, mainly siRNA and deletion mapping. Genome-wide knockdown studies involve systematic knockdown or deletion of genes or segments of the genome. This is generally done in prokaryotes or in a tissue culture environment due to the massive number of knockdowns that must be performed. After the systematic knockout is completed (and possibly confirmed by mRNA expression analysis), the phenotypic results of the knockdown/knockout can be observed. Observation parameters can be selected to target a highly specific phenotype. The resulting dataset is then queried for samples which exhibit phenotypes matching the disease in question – the gene(s) knocked down/out in said samples can then be considered candidate disease genes for the individual in question. Whole exome sequencing Whole exome sequencing is a brute-force approach that involves using modern day sequencing technology and DNA sequence assembly tools to piece together all coding portions of the genome. The sequence is then compared to a reference genome and any differences are noted. After filtering out all known benign polymorphisms, synonymous changes, and intronic changes (that do not affect splice sites), only potentially pathogenic variants will be left. This technique can be combined with other techniques to further exclude potentially pathogenic variants should more than one be identified. See also Gene Disease Database Gene identification Haplotype tagging References Mutation Genomics Molecular biology Bioinformatics