GENETIC MAPPING OF THREE LARGE CONSANGUINEOUS KASHMIRI FAMILIES WITH AUTOSOMAL RECESSIVE POLYDACTYLY SCREENED FOR FIVE PREVALENT GENES

Background: Polydactyly, a congenital hand defect characterized by extra digits, is more complicated than simple duplication, delicately weaving aberrant anatomical components with hypoplasia, uneven joint shapes, and unusual tendon and ligament placements. The dominant theory attributes its genesis to a group of five genes: GLI1 (chromosome 12q13.3), ZNF141 (chromosome 4p16.3), IQCE (chromosome 7p22.2), KIAA0825 (chromosome 5q15), and FAM92A (chromosome 8q22.1). The objective of this study is to identify the most prevalent genes responsible for polydactyly in the population of Azad Jammu and Kashmir. Method: The microsatellite markers used for PCR amplification and subsequently testing linkage to known genes are presented below. Represent electropherograms of ethidium bromide-stained 8% non-denaturing polyacrylamide gels (PAGEs) obtained by genotyping microsatellite markers linked on chromosome 8q22.1, 5q15, 12q13.3, 4p16.3, and 7p22.3 in family A, B, C. Genetic positions (in centiMorgan) for these marker loci were obtained from Rutgers combined linkage-physical map of the human genome. Results: Screening of most prevalent genes that include GLI1 (chromosome 12q13.3), ZNF141 (chromosome 4p16.3), IQCE (Chromosome 7p22.2), KIAA0825 (chromosome 5q15) and FAM92A (8q22.1) showed heterozygosity on every locus. Already known disease loci were further narrowed down with highly polymorphic markers which failed to find any linkage. Conclusion: The previously reported genotypic-phenotypic relation was not revealed in these 3 families signifying the probable involvement of unexplored genetic segments in intricate pathogenesis of this condition, emphasizing the need for further exploration beyond the established genetic association. Pak J Physiol 2024;20(3):44–8, DOI: https://doi.org/10.69656/pjp.v20i3.1611