C origin. The variation type annotations are made based on whether the variation is of genetic or non-genetic origin. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28300835 Genetic terms are used for alterations originating from the genetic material of the organism (DNA or RNA, depending on the organism), while terms with non-genetic origin are either artificial or originated from the processing of RNA or protein molecules without change in the corresponding DNA.additional features of the instances in a database in a systematic way. It may be tiring for a human reader to see the same concept every time it is mentioned, however, for computational analyses it is a blessing and facilitates fast searches. For the annotation we are developing a tool called VariOtator [18]. Here is a real life example of variation in the AIRE gene leading to the autoimmune polyendocrine syndrome type 1 (APS-1) also called for APECED disease (autoimmune polyendocytopathy-candidiasis-ectodermal dystrophy), an autoimmune polyendocrine syndrome. AIRE, autoimmune regulator, is a transcriptional regulator of tissue-specific antigens. Variations affect the regulation, leading to the production of self-reactive antigens. The T > C variation leading to a L to P BX795 price substitution in the homogeneous staining region (HSR) domain is disease causing [19] (AIREbase [20,21] entry A0087). The functional and other aspects of APECED-causing variations were further studied in [22]. The genomic variant g.4789 T > C in the IDbase reference sequence D0003 (http://structure. bmc.lu.se/cgibin/fetch_idrefseq.cgi?ac = D0003 format = embl, crossreference to EMBL:AB006682) is annotated as follows. VariO:0128 VariO:0129 VariO:0322 VariO:0135 VariO:0136 VariO:0313 VariO:0314 variation affecting DNA DNA variation type DNA variation classification DNA chain variation DNA substitution transition pyrimidine transitionThe variation is of genetic origin VariO:0128 VariO:0129 VariO:0127 VariO:0130 variation affecting DNA DNA variation type DNA variation origin DNA variation of genetic originThere is a pyrimidine transition of genetic origin. The effect to RNA sequence (IDbase reference sequence C:0003 http://structure.bmc.lu.se/cgi-bin/fetch_idrefseq. cgi?ac = C0003 cross referenced to EMBL; AB006682) is, similar at DNA level, a pyrimidine transition, which causes a missense variation. VariO:0297 VariO:0306 VariO:0328 VariO:0312 VariO:0313 VariO:0314 VariO:0308 variation affecting RNA RNA variation type RNA variation classification RNA substitution transition pyrimidine transition missense variationOn the protein level the reference sequence is UniProt entry O43918. A variation has different annotations at different levels. In this example, the amino acid substitution at protein level is annotated as DNA substitution on DNA level, and on RNA level as RNA nucleotide substitution of type missense variation. The annotations are richer on protein level as the effects of the variation affect protein function, structure and properties.Vihinen Journal of Biomedical Semantics 2014, 5:9 http://www.jbiomedsem.com/content/5/1/Page 4 ofVariO:0002 VariO:0012 VariO:0325 VariO:variation affecting protein protein variation type protein variation classification amino acid substitutionThe variant affects transactivation inactivating the protein function. The property term (effect on protein activity) is again modified by the attribute (missing). VariO:0002 variation affecting protein VariO:0032 variation affecting protein property VariO:0053 effect on protein activity; Va.