Kanwal Anwar

SRD5A2 Heterozygous Mutation in Identifying the Genetic Basis in Ambiguous Genitalia


Abstract:

Steroid 5 alpha-reductase type 2 (SRD5A2) encodes the SRD5A2 enzyme, which is responsible for the conversion of testosterone to a more potent dihydrotestosterone (DHT) hormone. It has an important role in the development of male external genitalia and regulates the mechanism of androgen hormones in males. Mutations in SRD5A2 cause steroid-5alpha-reductase deficiency resulting in masculinization defects and polymorphism. Steroid-5alpha-reductase is a rare autosomal disorder in 46-XY individuals, who are genetically male but phenotypically resemble females. The objective of our study is the mutational analysis of SRD5A2 gene to identify mutants responsible for the development of ambiguous sexual orientation in intersex. In addition, we will also examine gene expression of SRD5A2 among 46-XY intersex people of Pakistan. For this purpose, we have extracted DNA and RNA for mutational analysis and gene expression of SRD5A2 gene respectively. Further, RT-PCR and Sanger sequencing will be performed for analysis of the results. The mutations identified in the hotspot region of exon 1 and 4 regions fail to form DHT, thus testosterone will not bind effectively with the Androgen receptor (AR) and a deficiency of the SRD5A2 enzyme in the subjects might be a cause of ambiguous genitalia and polymorphism. 

Lab expertise:

 DNA extraction, RNA extraction , cDNA synthesis, Polymerase chain Reaction (PCR), Primer designing, Biorender, Purification of DNA sample for sequencing.


Inspiration

BIOT 22 batch