Identifying Highly Penetrant Disease Causal Mutations Using Next Generation Sequencing: Guide to Whole Process

Table 4

What is needed for a genetic study?

Material	Notes
“Sufficient” number of high-quality sequencing/genotype data	Amount needed can vary from one proband and a few family members (for very rare Mendelian disorders) to thousands of cases and controls (for certain common complex disorder/traits)
List of candidate genes	Websites such as http://omim.org/ and http://ghr.nlm.nih.gov/; and software such as SNPs3D can be helpful
Identification of variant calling tool	Such as in Table 2
Identification of variant effect predictor tool	Such as in Table 3; tools usually require conversion of VCF to VEP format (Ensembl website)
Knowledge of human population variation databases	That is, HapMap, 1000 Genomes Project, EVS, dbSNP, and internal databases
Knowledge of databases storing information about genes and their products	That is, OMIM, Gene (NCBI), GeneCards, Unigene (NCBI), GEO Profiles (NCBI), HomoloGene (NCBI), and Mouse knockout databases (such as http://www.informatics.jax.org/, http://www.tigm.org/database/ and http://www.nc3rs.org.uk/category.asp?catID=8). Search the literature using PubMed and/or Web of Science.

The most important factors when carrying out a genetic association study are (i) the availability of reliable data (ii) bioinformatics and biological expertise, and (iii) careful planning.