Sex determination network in mammals- finding the missing pieces

Sex determination is the process through which an organism develops as male or female. DSDs (disorders of sex development) are defined as congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. DSD affects 1 : 2,500-4,000 newborns.

Most of the genes involved in the process of sex determination are well known, and still, in over 50% of DSD cases, a diagnosis is not found using Whole Exome Sequencing. It is highly likely that many of these causing mutations lie within the noncoding parts of the genome. Additionally, we still do not understand the interplay and hierarchy among the key transcription factors controlling sex determination and their target genes. Challenges in studying DSD include limitation of cell numbers that can be obtained from embryonic gonads and the ability to isolate pure population of gonadal cell types.

Our aim is to explore the genes and regulatory elements bound and regulated by the key transcription factors controlling gonadal development and better describe the interplay between the key factors involved in sex determination. We will use the low input Cut & Run method to identify the target genes and genomic sequences of all the main pro male transcription factors. In order to analyze the expression state of these genes we will generate RNA seq data in parallel to Cut and RUN analysis.

Better understanding of these gene regulatory networks can improve the diagnosis rate of DSD patients and offer better treatment strategies as well as prenatal and pregestational diagnosis options.