Comparative Genomic Analysis of Human HADHB and WNT5A Gene Containing Loci to Elucidate their Gene Regulatory Networks

Abstract

In developmental biology, the limb is an extensively used model organ. Prominent variances in the morphological structure of limbs among different species are observed, even though the signaling paths involved during the limb development are mainly conserved. This reveals that gene regulation plays a major role in limb patterning. The process of genome-wide identification of the genes and their regulatory elements, which are involved in the development and growth of limbs has been alleviated by the latest advancements in the field of genomics. Variations in gene expression that can direct to crucial limb morphological alterations in evolution, for example fm-to-limb reformation, loss of limbs in snakes and acquisition of wing in bats, are triggered by the modifications in the gene regulatory elements (mainly Cis-acting elements). Additionally, accumulation of evidence demonstrates that the disturbance of certain gene regulatory elements particularly enhancers leads to the production of unique limb deformities. Thus, it is evident from latest researches that the remote cis-regulatory elements mediate the spatiotemporal control of gene expression, which forms the basis of regular limb development. Though enhancers perform a fundamental part in evolution and minor changes in the enhancer sequence or dosage may lead to functional or structural limb malformation, their detection continues to be elusive mainly due to complexities in accomplishing an extensive pairing of enhancers and target genes. Several different comparative genomics techniques, both wet and computational, have been in use for en4.anced interpretation and understanding of the enhancer structure and function. Conclusively, one significant comparative genomics technique developed and used to analyze the conservation pattern of limb specific enhancers of human chromosome 2 and 3 and to link them to their target genes, is synteny mapping, which cleared route for better systematic study of their roles in evolution and diseases.