METHODS: The full genomic sequences of all known different RV-A and -B prototypes were downloaded from the National Centre for Biotechnology Information (NCBI) and divided into minor low-density lipoprotein receptor (LDLR) and major intercellular adhesion molecule groups (ICAM). The sequences were edited using Biological Sequence Alignment Editor, v 7.2.0 (BioEdit software) to study each capsid protein (VP1, VP2, VP3, and VP4) and analyzed using the EMBL-EBI ClustalW server and the more current Clustal Omega tool for the calculation of the identities and similarities.
RESULTS: We analyzed and predicted immunogenic motifs from capsid proteins that are conserved across distinct RV serotypes using a bioinformatics technique. The amino acid sequences of VP3 were found to be the most varied, while VP4 was the most conserved protein among all RV-A and RV-B strains. Among all strains studied, RV-74 demonstrated the highest degree of homology to other strains and could be a potential genetic source for recombinant protein production. Nine highly conserved regions with a minimum length of 9-mers were identified, which could serve as potential immune targets against rhinoviruses.
CONCLUSION: Therefore, bioinformatics analysis conducted in the current study has paved the way for the selection of immunogenic targets. Bioinformatically, the ideal strain's capsid protein is suggested to contain the most common RVs immunogenic sites.
RESULTS: A significant nonparametric linkage (NPL) score was detected in family 100. Other suggestive NPL and logarithm of the odds (LOD) scores were attained from families 50, 58, 99 and 100 under autosomal recessive mode. Heterogeneity LOD (HLOD) score ≥ 1 was determined for all families, confirming genetic heterogeneity of the population and indicating that a proportion of families might be linked to each other. Several candidate genes in linkage intervals were determined; LPHN2 at 1p31, SATB2 at 2q33.1-q35, PVRL3 at 3q13.3, COL21A1 at 6p12.1, FOXP2 at 7q22.3-q33, FOXG1 and HECTD1 at 14q12 and TOX3 at 16q12.1.
CONCLUSIONS: We have identified several novel and known candidate genes for nonsyndromic cleft lip and/or palate through genome-wide linkage analysis. Further analysis of the involvement of these genes in the condition will shed light on the disease mechanism. Comprehensive genetic testing of the candidate genes is warranted.