In Silico identification of a common mobile element insertion in exon 4 of RP1.
Sci Rep
; 11(1): 13381, 2021 06 28.
Article
em En
| MEDLINE
| ID: mdl-34183725
ABSTRACT
Mobile element insertions (MEIs) typically exceed the read lengths of short-read sequencing technologies and are therefore frequently missed. Recently, a founder Alu insertion in exon 4 of RP1 has been detected in Japanese patients with macular dystrophy by PCR and gel electrophoresis. We aimed to develop a grep search program for the detection of the Alu insertion in exon 4 of RP1 using unprocessed short reads. Among 494 unrelated Korean patients with inherited eye diseases, 273 patients with specific retinal phenotypes who were previously genotyped by targeted panel or whole exome sequencing were selected. Five probands had a single heterozygous truncating RP1 variant, and one of their unaffected parents also carry this variant. To find a hidden genetic variant, whole genome sequencing was performed in two patients, and it revealed AluY c.4052_4053ins328/p.(Tyr1352Alafs*9) insertion in RP1 exon 4. This AluY insertion was additionally identified in other 3 families, which was confirmed by PCR and gel electrophoresis. We developed simplified grep search program to detect this AluY insertion in RP1 exon 4. The simple grep search revealed a median variant allele frequency of 0.282 (interquartile range, 0.232-0.383), with no false-positive results using 120 control samples. The MEI in RP1 exon 4 was a common founder mutation in Korean, occurring in 1.8% of our cohort. The RP1-Alu grep program efficiently detected the AluY insertion, without the preprocessing of raw data or complex installation processes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Elementos de DNA Transponíveis
/
Éxons
/
Sequências Repetitivas Dispersas
/
Proteínas Associadas aos Microtúbulos
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article