title: An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) gene.
abstract: Coding variants in tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) have been implicated in common variable immunodeficiency (CVID), but the functional effects of such mutations in relation to the development of the disease have not been entirely established. To examine the potential contribution of TNFRSF13B variants to CVID, we have applied an evolutionary approach by sequencing its coding region in 451 individuals belonging to 26 worldwide populations, in addition to controls, patients with CVID and selective IgA deficiency (IgAD) from Italy. The low level of geographical structure for the observed genetic diversity and the several neutrality tests performed confirm the absence of recent population-specific selective pressures, suggesting that TNFRSF13B may be involved also in innate immune functions, rather than in adaptive immunity only. A slight excess of rare derived alleles was found in patients with CVID, and thus some of these variants may contribute to the disease, implying that CVID probably fits the rare variants rather than the common disease/common variant paradigm. This also confirms the previous suggestion that TNFRSF13B defects alone do not cause CVID and that such an extremely heterogeneous immunodeficiency might be more likely related to additional, still unknown environmental and genetic factors.
authors.affiliation: Dipartimento di Biologia Evoluzionistica Sperimentale, Area Antropologia, Università di Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sazzini
authors.forename: R
authors.initials: R
authors.lastname: Zuntini
authors.forename: S
authors.initials: S
authors.lastname: Farjadian
authors.forename: I
authors.initials: I
authors.lastname: Quinti
authors.forename: G
authors.initials: G
authors.lastname: Ricci
authors.forename: G
authors.initials: G
authors.lastname: Romeo
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: F
authors.initials: F
authors.lastname: Calafell
authors.forename: D
authors.initials: D
authors.lastname: Luiselli
mesh_terms: D000818:Animals; D005075:Biological Evolution; D016022:Case-Control Studies; D017074:Common Variable Immunodeficiency / Q000453:epidemiology / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D014943:Global Health; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation / Q000235:genetics*; D002679:Pan troglodytes / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics*
chemical_list: C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein