Identification of the genetic cause for quadrupedal locomotion in human subjects by high- throughput sequencing
Rare form of autosomal recessive congenital ataxia with severe mental retardation, quadrupedal locomotion, absence of speech and signs of hirsutism was identified in Brazilian family with a consanguineous marriage. We performed convergent genetic analysis of affected descendants and their healthy relatives using Affymetrix Genome-Wide Human SNP Array 6.0 and a whole genome sequencing using Illumina platform. Microarray data analysis identified the set of homozygous genomic loci linked to the disease. In follow up whole genome sequencing we analyzed the homozygous regions and identified the large homozygous deletion disrupting one of the gene for putative neurotransmitter receptor.
To study evolution of the gene the protein–coding sequence of the gene across 43 species was examined by branch and branch-site specific models of Likelihood Ratio Test by PAML software. Next, non-coding elements conserved between the primates (phastConsElements46wayPrimates, UCSC tables) in 1 Mb region harboring the gene were examined by pairwise comparison using Tajima’s Relative Rate Test included in MEGA software package. Our study revealed the genetic defect eliminating evolutionary conserved part of the gene leading to impairment of human-specific trait for locomotion and intellect and identified the trajectory of evolutionary changes of this gene in human lineage.