Genetika 2017 Volume 49, Issue 1, Pages: 63-76
https://doi.org/10.2298/GENSR1701063Y
Full text ( 679 KB)
Application of computational algorithms to assess the functionality of non-synonymous substitutions in MHC DRB gene of Nigerian goats
Yakubu Abdulmojeed (Nasarawa State University, Department of Animal Science, Keffi, Shabu-Lafia Campus, Lafia, Nigeria + University of Ibadan, Department of Animal Science, Animal Breeding and Genetics Laboratory, Ibadan, Nigeria + Cornell University, College of Agriculture )
Salako Adebowale E. (University of Ibadan, Department of Animal Science, Animal Breeding and Genetics Laboratory, Ibadan, Nigeria)
de Donato Marcos (Universidad de Oriente, Cornell University, College of Agriculture and Life Sciences, Animal Genetics and Genomics Laboratory, International Programs, Ithaca, USA + Instituto de Investigaciones en Biomedicina y Ciencias Aplicadas, Laboratorio Genetica Mol)
Imumorin Ikhide G. (Cornell University, College of Agriculture and Life Sciences, Animal Genetics and Genomics Laboratory, International Programs, Ithaca, USA)
The Major Histocompatibility Complex (MHC) contains highly variable
multi-gene families, which play a key role in the adaptive immune response
within vertebrates. Among the Capra MHC class II genes, the expressed DRB
locus is highly polymorphic, particularly in exon 2, which encodes the
antigen-binding site. Models of variable non-synonymous/synonymous rate
ratios among sites may provide important insights into functional constraints
at different amino acid sites and may be used to detect sites under positive
selection. Many non-synonymous single nucleotide polymorphisms (nsSNPs) at
the DRB locus in goats are suspected to impact protein function. This study,
therefore, aimed at comparing the efficiency of six computational approaches
to predict the likelihood of a particular non-synonymous (amino acid change)
coding SNP to cause a functional impact on the protein. This involved the use
of PANTHER, SNAP, SIFT, PolyPhen-2, PROVEAN and nsSNPAnalyzer bioinformatics
analytical tools in detecting harmful and beneficial effects at H57G, Y89R,
V104D and Y112I substitutions in the peptide binding region of the DRB gene
of Nigerian goats. The results from PANTHER analysis revealed that H57G, Y89R
and Y112I substitutions (Pdeleterious= 0.113, 0.204 and 0.472, respectively)
were beneficial; while that of V104D was deleterious (Pdeleterious= 0.756),
an indication that it was non-neutral. As regards the SNAP approach, H57G and
Y89R substitutions were returned neutral with expected accuracy of 53 and
69%, respectively while V104D and Y112I substitutions were harmful. H57G and
Y89R substitutions were also found harmless in the SIFT analysis. However,
only H57G (PROVEAN) and V104D (nsSNPAnalyzer) amino acid substitutions were
found to be beneficial. Interestingly, the predicted 3D structures of both
native and mutant DRB protein appeared similar as validated by Ramachandran
plots. The consensus reached by PANTHER, SNAP, SIFT and PolyPhen-2 approaches
on the neutrality especially of H57G (PROVEAN inclusive) and Y89R amino acid
substitutions may be used in search of disease resistant genotypes at the DRB
locus of Nigerian goats.
Keywords: bioinformatics tools, DRB gene, Goats, Nigeria, Non-synonymous substitutions