-This track shows variants associated with monogenic congenital defects of immunity to SARS-CoV-2, -virus with incomplete or complete penetrance from the COVID Human Genetic Effort. This international consortium aims -to detect rare or common monogenic inborn immunity errors (IEI) underlying severe forms of COVID-19 -in previously healthy individuals, as well as rare or common monogenic variations that make certain -individuals resistant to infection by SARS-CoV2 virus despite repeated exposure. ++Unlike a regular genome browser track, the COVID-19 Immunity Variants track displays all ++affected genes in multi-region view, ++showing the variants within the coordinates of the gene, but hiding all the intergenic bases. To ++return to the default Genome Browser view, click on the "-" button next to the "region" box. +
- --The major feature of the small set of variants in this track is that they are functionally tested -to be deleterious and genetically tested to be disease-causing. Specifically, -rare variants were predicted to be loss-of-function (LOF) at 13 human loci known to govern -TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus in patients with -life-threatening COVID-19 pneumonia, relative to subjects with asymptomatic or benign infection. -These genetic defects display incomplete penetrance for influenza respiratory distress and only -manifested clinically upon infection with the more virulent SARS-CoV-2. -
- -+ Only eight genes and few variants are contained in this track. Use the links in the table to + browse the gene of interest: +
+ +| Gene Name | +Human GRCh37/hg19 Assembly | +Human GRCh38/hg38 Assembly | +
|---|---|---|
| TLR3 | ++ chr4:186990309-187006252 | ++ chr4:186069152-186088069 | +
| IRF7 | ++ chr11:612555-615999 | ++ chr11:612591-615970 | +
| UNC93B1 | ++ chr11:67758575-67771593 | ++ chr11:67991100-68004097 | +
| TBK1 | ++ chr12:64845840-64895899 | ++ chr12:64452120-64502114 | +
| TICAM1 | ++ chr19:4815936-4831754 | ++ chr19:4815932-4831704 | +
| IRF3 | ++ chr19:50162826-50169132 | ++ chr19:49659570-49665875 | +
| IFNAR1 | ++ chr21:34697214-34732128 | ++ chr21:33324970-33359864 | +
| IFNAR2 | ++ chr21:34602231-34636820 | ++ chr21:33229974-33264525 | +
+ Variant calls in 12 autosomal IFN-related genes from whole exome or genome data with a MAF lower + than 0.001 (gnomAD v2.1.1) and experimental demonstration of loss-of-function (LOF) were considered + for statistical analysis. The proportion of individuals carrying at least one pLOF variant was + compared between cases and controls by means of logistic regression with the likelihood ratio test. + The first three principal components of the PCA were included in the logistic regression model + to account for ethnic heterogeneity of the cohorts. + Analysis of enrichment in rare (MAF < 0.001) synonymous + variants of the 12 genes was performed to check the calibration of the burden test. PCA was + conducted with Plink v1.9 software on whole exome and genome sequencing data and 1000 Genomes (1kG) + Project phase 3 public database as reference, using 27,480 exonic variants with a minor allele + frequency >0.01 and a call rate >0.99. The odds ratio was also estimated by logistic regression + and adjusted for ethnic heterogeneity. +
+ ++ The raw data can be explored interactively with the + Table Browser, or the Data Integrator. + Please refer to + our mailing list archives for questions, or our Data Access FAQ for more information. +
+ ++ Thanks to the COVID Human Genetic Effort contributors for making these data available, and in + particular to Qian Zhang at the Rockefeller University for review and input during browser track + development. +
+ - ++ Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C + et al. + + Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. + Science. 2020 Sep 24;. + PMID: 32972995 +
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