Targeting the Non-Coding Genome for the Diagnosis of Disorders of Sex Development.
Sex Dev
; 15(5-6): 392-410, 2021.
Article
em En
| MEDLINE
| ID: mdl-34634785
ABSTRACT
Disorders of sex development (DSD) are a complex group of conditions with highly variable clinical phenotypes, most often caused by failure of gonadal development. DSD are estimated to occur in around 1.7% of all live births. Whilst the understanding of genes involved in gonad development has increased exponentially, approximately 50% of patients with a DSD remain without a genetic diagnosis, possibly implicating non-coding genomic regions instead. Here, we review how variants in the non-coding genome of DSD patients can be identified using techniques such as array comparative genomic hybridization (CGH) to detect copy number variants (CNVs), and more recently, whole genome sequencing (WGS). Once a CNV in a patient's non-coding genome is identified, putative regulatory elements such as enhancers need to be determined within these vast genomic regions. We will review the available online tools and databases that can be used to refine regions with potential enhancer activity based on chromosomal accessibility, histone modifications, transcription factor binding site analysis, chromatin conformation, and disease association. We will also review the current in vitro and in vivo techniques available to demonstrate the functionality of the identified enhancers. The review concludes with a clinical update on the enhancers linked to DSD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos do Desenvolvimento Sexual
/
Desenvolvimento Sexual
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sex Dev
Assunto da revista:
CIENCIAS DO COMPORTAMENTO
Ano de publicação:
2021
Tipo de documento:
Article