To annotate variants with respect to their functional consequences on genes, ANNOVAR needs to download gene annotation data sets (gene/transcript annotations and FASTA sequences) from the UCSC Genome Browser (12) and save them to local disk. Several different gene annotation systems, including RefSeq genes, UCSC Genes and the Ensembl genes, can be utilized for annotation. The ‘–downdb’ argument can be utilized for downloading necessary files automatically, if the computer is connected to the Internet. The ‘wget’ system command will be utilized for downloading, or the Net::Ftp/LWP::UserAgent modules (standard Perl modules installed in most systems by default) can be alternatively utilized. The users can specify different genome builds, such as hg18 (human), mm9 (mouse) or bosTau4 (cow), as long as they are available from the UCSC Genome Browser annotation databases. When performing gene-based annotations by Ensembl gene definitions (13), ANNOVAR will download the FASTA sequences from Ensembl as they were not available from the UCSC Genome Browser.
