Computational STAT4 rSNP Analysis, Transcriptional Factor Binding Sites And Disease

Abstract

Purpose -Signal Transducer and Activator of Transcription 4 (STAT4) is important for signaling by interleukins and type 1 interferons and has been found to have several simple nucleotide polymorphisms (SNPs) associated with human disease. STAT4 SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to human disease. Methods -The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. TheVector NTI Advance 11.5 computer program was employed in locating all the TFBS in the STAT4 gene from 4 kb upstream of the transcriptional start site to 8.3 kb past the 3'UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS.Results -The STAT4 SNPs in the 70 kb intron between exon 2 and 3 are in linkage disequilibrium and have previously been found to be significantly associated with several vasculitis diseases as well as diabetes. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the STAT4 gene. These STAT4 SNPs should be considered as regulatory (r) SNPs.Conclusion -The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF STAT4 regulation. These regulatory changes were discussed with respect to changes in human health that result in disease.

Unraveling Admixture, Inbreeding, and Recent Selection Signatures in West African Indigenous Cattle Populations in Benin

“…The region 111.5–111.5 Mb on BTA5 contributed to positive selection for natural virus resistance and to extensive admixture in West Sahelian African human populations ( Cagliani et al, 2011 ; Pérez-Rivas et al, 2014 ; Triska et al, 2015 ). In addition, the segment BTA 2:70–71 Mb covered various candidate genes such as EN1 , involved in growth traits in cattle ( Buroker, 2014 ). Further regions under selection in BO_cur host candidate genes, significantly associated with different traits, including ADAM32 , ADAM9 , HTRA4 , and KLHL21 with residual feed intake and immune responses, PLEKHA2 and TNFRSF25 with growth and carcass performances, HTRA4 with milk, and HOOK1 with heat stress ( Fan et al, 2015 ; Tizioto et al, 2015 ; Seong et al, 2016 ; Blanco et al, 2017 ; Hardie et al, 2017 ; Hay and Roberts, 2018 ; Sengar et al, 2018 ; Skibiel et al, 2018 ; Oliveira et al, 2019 ; Braz et al, 2020 ; Brunes et al, 2021 ; Soares et al, 2021 ).…”

The 10 bp duplication insertion/deletion in the promoter region within paired box 7 gene is associated with growth traits in cattle

“…According to the bioinformatics analysis, this 10 bp indel region might bind several critical transcription factors relating to growth and development, such as ZNF354C (Zfp354C). ZNF354C is an osteoblast-specific transcription factor that might take an active part in metabolism, cell proliferation, differentiation and development, and gene expression (Du and Hao, 2014;Wang et al, 2012;Buroker, 2016). ZNF354C specifically interacted with FAM20C and might also affect osteoblast differentiation by downregulating this factor (Du and Hao, 2014).…”