Challenges facing repeat expansion identification, characterisation, and the pathway to discovery.
Emerg Top Life Sci
; 7(3): 339-348, 2023 Dec 14.
Article
em En
| MEDLINE
| ID: mdl-37888797
ABSTRACT
Tandem repeat DNA sequences constitute a significant proportion of the human genome. While previously considered to be functionally inert, these sequences are now broadly accepted as important contributors to genetic diversity. However, the polymorphic nature of these sequences can lead to expansion beyond a gene-specific threshold, causing disease. More than 50 pathogenic repeat expansions have been identified to date, many of which have been discovered in the last decade as a result of advances in sequencing technologies and associated bioinformatic tools. Commonly utilised diagnostic platforms including Sanger sequencing, capillary array electrophoresis, and Southern blot are generally low throughput and are often unable to accurately determine repeat size, composition, and epigenetic signature, which are important when characterising repeat expansions. The rapid advances in bioinformatic tools designed specifically to interrogate short-read sequencing and the development of long-read single molecule sequencing is enabling a new generation of high throughput testing for repeat expansion disorders. In this review, we discuss some of the challenges surrounding the identification and characterisation of disease-causing repeat expansions and the technological advances that are poised to translate the promise of genomic medicine to individuals and families affected by these disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biologia Computacional
/
Sequências de Repetição em Tandem
Limite:
Humans
Idioma:
En
Revista:
Emerg Top Life Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Austrália