Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus
Küçük Resim Yok
Tarih
2019
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Nature Portfolio
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.
Açıklama
Anahtar Kelimeler
Interferon Regulatory Factor, De-Novo Mutations, Gene-Expression, Kinase Blk, Erythematosus, Protein, Association, Lyn, Src, Activation
Kaynak
Nature Communications
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
10
