Currarino triad syndrome is an autosomal dominant inherited disease, caused by mutations in the human MNX1 gene, where the mutants have anorectal malformations and other symptoms. Mutations in the MNX1 influences the translation of MNX1 protein which is a homeobox protein responsible for the morphogenisis during embrionic development. Since MNX1 is very sensitive to the mutations, there is no paper that discuss the evolutionary history of MNX1 instead of the clinical experiments and discussions related to the disease. Therefore, the research is broaden to gene HB9 which is the origin of MNX1, where vertebrate HB9 is MNX1. The attached paper discuss the relatedness of HB9 and another homeobox gene MNR2 which are results of a gene duplication event and reports a homologue of these genes that is diverged before the gene duplication and belongs to a non-vertebrate specie. With the inspiration of this paper, homologuous sequences for HB9 protein will be aligned, paralogs and orthologs will be identified and phylogenetic tree will be used to decide for the conservation score computation so that only relevant homologous sequences will be considered during conservation score computation. According to those conservation scores, it will be observed whether the sites that Currarino triad syndrome causing mutations occur in the most conserved regions among species. This observation will be repeated for the other disease-causing mutations from ClinVar database and neutral mutations from Gnomad database as well.
Paper on evolutionary history of HB9 Additional paper that might be facilitated