Multiple rare genetic variants co-segregating with familial IgA nephropathy all act within a single immune-related network

Autor:	S N, Cox, F, Pesce, J S, El-Sayed Moustafa, F, Sallustio, G, Serino, C, Kkoufou, A, Giampetruzzi, N, Ancona, M, Falchi, F P, Schena
Rok vydání:	2016
Předmět:	gene polymorphism Genetic Linkage Genome Human kidney disease Glomerulonephritis IGA Sequence Analysis DNA Original Articles Pedigree family medicine Genomic Structural Variation Humans Exome Genetic Predisposition to Disease Original Article genetics glomerulonephritis
Zdroj:	Journal of Internal Medicine
ISSN:	1365-2796
Popis:	Background IgA nephropathy (IgAN) is a common complex disease with a strong genetic involvement. We aimed to identify novel, rare, highly penetrant risk variants combining family‐based linkage analysis with whole‐exome sequencing (WES). Methods Linkage analysis of 16 kindreds of South Italian ancestry was performed using an ‘affected‐only’ strategy. Eight most informative trios composed of two familial cases and an intrafamilial control were selected for WES. High‐priority variants in linked regions were identified and validated using Sanger sequencing. Custom TaqMan assays were designed and carried out in the 16 kindreds and an independent cohort of 240 IgAN patients and 113 control subjects. Results We found suggestive linkage signals in 12 loci. After sequential filtering and validation of WES data, we identified 24 private or extremely rare (MAF
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::4d63eda768172d7ca32d5bcbe06ba957 https://pubmed.ncbi.nlm.nih.gov/27730700 Zobrazit plný text záznamu Plný text