Comparative Genomic Analysis of Human GLRB and COL9Al Gene Containing Loci to Elucidate their Gene Regulatory Networks

Abstract

At different points in our evolutionary history the selection in opposite direction for each limb resulted in an exclusive feature for a primate, i.e. short arms and long legs. This distinctive and uncertain observation intrigues us to question our understanding regarding the correlation of evolvability and development, because there exists serial homology between limbs and thus their independent evolution should be coerced due ·to genetic interconnection. Different genes have been identified so far regarding limbs, for instance the development of limbs is controlled by Hox genes, predominantly the clusters of HoxA and HoxD, which are concerned with the regeneration abilities of limbs. In addition, fore and hind limbs are reported to have a distinctive expression pattern of HoxD, that is considered to have possibly caused evolution of wings. The cis-acting regulatory control of significant genes that control the development and patterning of limbs is very vague and thus it is supposed that this type of control might be involved in the modification of limb morphology during vertebrate history. Non-coding regulatory elements i.e. enhancers greatly increase the activities of many promoters and exert a positive influence on transcription. The major challenge is to pair enhancers with target genes, which leads to the evasive characterization of the former. To leverage the increased accessibility of the data of functional genomics and enhance the mechanical concepts of action of enhancer, several wet lab and computational methods are implied. Large scale synteny mapping is considered fundamental for comparative genomics as its algorithm development has been made possible due to the availability of human and mouse genome. The gene order and homology between the genes for the genomes of different species are observed through the framework provided by the synteny. The conservation of synteny helps in extending the studies regarding genome evolution and also provides valuable empirical insights for the investigation of families of the homologous genes. Considering the region of limb specific enhancers of human chromosome 4 and 6, to check variant presence in enhancer we overlapped enhancer region with disease variants. Further, we performed conservation analysis of enhancer and variant. Then we performed regional analysis on enhancer surrounding region. Also, we shortlisted limb specific genes from the region under scope and successfully drawn the synteny for analyzing syntenic conservation till mammals.