Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.
Cell Rep
; 43(7): 114376, 2024 Jul 23.
Article
en En
| MEDLINE
| ID: mdl-38900637
ABSTRACT
Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3-mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We apply an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in humans and mice. We unexpectedly discover an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts are altered in Shank3-mutant mice and postmortem brain tissues from individuals with autism spectrum disorder. The enhanced SHANK3 transcriptome significantly improves the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest that both deterministic and stochastic transcription of the genome is associated with SHANK family genes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastorno Autístico
/
Proteínas del Tejido Nervioso
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos