Research Unit, Tampere University Hospital, Tampere, FinlandFor the Immunogenetics Special IssueImmunogenetics, the combination of immunology and geneticsto study molecular and genetic bases of the immune system andresponse in health and disease, is becoming ever more importantand interesting. New immunology related genes and functions aredescribed constantly. Currently, some 150 primary immuno-deficiencies (IDs) are known, and the genetic defect is identifiedin more than 100 diseases. The severity of immunodeficienciesvaries greatly. Most severe forms are fatal unless early and correctdiagnosis is made. Since the symptoms of many IDs are very similar,gene tests are in many cases essential for the definitive diagnosis.Immunological molecules have served as models in many fields.The first ID, X-linked agammaglobulinemia, was described in1952 [Bruton, 1952] and the first human ID-related mutationwas described in adenosine deaminase, more than 20 years ago[Bonthron et al., 1985]. The first gene identified by positionalcloning causes the X-linked form of chronic granulomatous disease(XCGD) [Royer-Pokora et al., 1986], and the first inheriteddisorder in which gene therapy was successfully applied was severecombined immunodeficiency (SCID) [Cavazzana-Calvo et al.,2000]. BTKbase was one of the first locus-specific mutationdatabases released [Vihinen et al., 1995]. Recently, studieshave revealed genotype–phenotype correlations in some IDs[Arredondo-Vega et al., 1998; Vihinen and Durandy, 2006].IDs are a heterogeneous group of predominantly rare inheriteddisorders affecting the immune system. Susceptibility to infectionsis the most characteristic feature of IDs, but symptoms ofimmunodeficiency patients are various, including autoimmunemanifestations, malignancies, and allergies. Therefore, immuno-genetics is a wide discipline and it is not possible to cover itcompletely in a few articles. This special issue of Human Mutationcomprises eight carefully selected articles that range from diagnosisto mutation analysis, describe molecular and genetic features ofimmunodeficiencies, and summarize several ID-related databases.Costabile et al. [2006] summarize the genetic diagnosticapproaches frequently used to identify mutations in ID genes.They discuss numerous procedures used in different laboratoriesaround the world. IDs are often difficult to diagnose due to similarand overlapping symptoms. According to European Society forImmunodeficiencies (ESID)/Pan-American Group for Immunode-ficiency (PAGID) recommendations, the definitive diagnosisshould sometimes be based on genetic analysis [Conley et al.,1999]. In the article, the benefits and problems of the differentmutation scanning and screening approaches are discussed. Theyalso suggest direct sequencing of cDNA and confirmation of theexon sequence as an economical approach for ID diagnosis.Two reviews deal with the genes and processes involved inproducing the huge variability of immunological recognitionmolecules. Recombination activating genes (RAGs) 1 and 2 areessential for V(D)J gene fragment recombination. Sobacchi et al.[2006] discuss the recombination process and the function of RAGs.They report also 18 novel RAG1 and 6 RAG2 mutations, 13 ofwhich are unique. Mutations in these proteins lead either to SCID orOmenn syndrome (OS). Sobacchi et al. [2006] also discuss in detailall the known atypical RAG-dependent ID cases. They concludethat RAG mutations lead to broad range of disease phenotypes.The final steps of antibody maturation, class switch recombina-tion (CSH) and somatic hypermutation (SHM) produce anti-bodies with high affinity. Several proteins take part in theseprocesses, including activation-induced cytidine deaminase (AID).AID mutations lead to hyper-immunoglobulin (Ig)M syndrome(HIGM), in which the antibody diversification is defective.Durandy et al. [2006] review AID-related HIGM. They discussinteresting genotype–phenotype correlations in which the locationof the mutation within the protein causes the ID either due todefective CSR or SHM, or both.This special issue contains three database articles. Robinsonet al. [2006] describes the IMGT/HLA and IPD databases forhuman major histocompatibility complex (MHC) variations andpolymorphic genes in the immune system, respectively. The datawere gathered via direct submissions or by mining of numerousdatabases. The authors describe the design principles, structure,and contents of the databases.Piirila¨ et al. [2006] report mutation databases for 107 IDsand over 4,100 cases. These patient-based databases record, inaddition to genetic defect(s), also clinical features of the affectedindividuals to allow phenotype–genotype correlation analysis. Thegoal of the group is to provide up-to-date mutation information forall IDs unless a database for a disease already exists elsewhere. Thearticle includes also analysis of the mutation types on DNA andamino acid level as well as description of the database format,structure, and data representation, and a list of the databases alongwith mutation statistics.The article of Va¨liaho et al. [2006] is a detailed analysis ofmutations causing X-linked agammaglobulinemia caused bymutations in Bruton tyrosine kinase. The BTKbase was the veryfirst ID database [Vihinen et al., 1995]. BTKbase contains dataon 1,111 patients, the largest being IDbase. The article covers thedatabase structure, content, and use, and concentrates on the data