GTH 2017, 61st Annual Meeting of the Society of Thrombosis and Hemostasis Research

The regulatory profile of the 5´ untranslated region of F13A1 gene of coagulation factor XIII (FXIII) A subunit

M. A. Jamil, S. Singh, V. Ivaskevicius, O. El-Maarri, J. Oldenburg, A. Biswas (Bonn, Germany)

Bleeding disorders, coagulation and fibrinolytic factors
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: To in silico screen the 5´ untranslated region of F13A1 gene in order to define putative regulatory genetic parameters governing transcription rates and hence FXIIIA subunit levels.

Methods: The 5´ untranslated region of F13A1 gene upstream of the transcription start site (till 5000 bp) was downloaded from ensemble database (www.ensembl.org ; accessed on 01.09.2016) (Ensemble ID: ENSG00000124491). The downloaded sequence was screened on the TRANSFAC platform to generate a list of putative regulatory transcription factor matrices corresponding to this region. Similarly a list of polymorphisms and CpG sequences occurring in this region were extracted by indicating the specific gene locus on the Biomart web tool (Ensemble gene 86; Ensemble Gene ID: ENSG00000124491; Ensemble transcript ID: ENST00000264870.7; http://www.ensembl.org/biomart/; accessed on 25.09.2016). The data was combined and analyzed for relevant overlap.

Results: A total of 246 SNPs were located in this region. Fifty CpG´s were found distributed across this region. One hundred and thirty TF matrices were predicted to bind in different parts of this region. Fifty eight of the 130 TF matrices were located on reported variants many of them deletions and insertions. Twenty seven of CpG´s were also located on reported variants. Only six TF matrices were found to be part of those CpG´s on which two SNPs have been reported (rs760544202 and rs3024306).

Conclusion: A high density of variability in this region is an indicator that it might be associated with the high level (almost 2-fold) of variability in FXIIIA antigen levels that is observed and reported from the general population. This data can be further investigated by screening the general population for these interesting variations or expressing them in an in vitro system.