The role of next generation sequencing in understanding male and female sexual development: clinical implications

ABSTRACT

Introduction: Next Generation Sequencing is revolutionising our understanding of variation in the human genome and as costs reduce the sequencing of patient’s genomes is become more routine.

Areas covered: Here, we review the current challenges in the field and some of the efforts that are underway to resolve them. We describe how these technologies are impacting on our understanding of human sex development and the profound clinical implications of these technologies on conditions such as Disorders of Sex Development (DSD).

Expert commentary: The sheer wealth of genomic data is generating new challenges—some are technical such as variant calling, or predicting the functional consequence of a variant—whereas others are more profound, such as establishing the link between extensive genomic information and the clinical presentation. Predicting disease phenotypes from genetic sequences is often extremely difficult because the genotype-phenotype relationship has proven to be far more complex than anticipated.

KEYWORDS:

• Next generation sequencing
• disorders of sex development (DSD)
• whole genome sequencing (WGS)
• whole exome sequencing (WES)
• gonad development

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

A Bashamboo is funded in part by the program Actions Concertees Interpasteuriennes (ACIP). Both authors are funded by a research grant from the EuroDSD in the European Community’s Seventh Framework Programme FP7/2007-2013 under grant agreement n° 201444 as well as grant N°295097 as part of the EU call FP7-INCO-2011-6. The work is also funded by a Franco-Egyptian AIRD-STDF grant.