Evaluation of genetic risk of apparently balanced chromosomal rearrangement carriers by breakpoint characterization.
J Assist Reprod Genet
; 41(1): 147-159, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-37993578
ABSTRACT
PURPOSE:
To report genetic characteristics and associated risk of chromosomal breaks due to chromosomal rearrangements in large samples.METHODS:
MicroSeq, a technique that combines chromosome microdissection and next-generation sequencing, was used to identify chromosomal breakpoints. Long-range PCR and Sanger sequencing were used to precisely characterize 100 breakpoints in 50 ABCR carriers.RESULTS:
In addition to the recurrent regions of balanced rearrangement breaks in 8q24.13, 11q11.23, and 22q11.21 that had been documented, we have discovered a 10-Mb region of 12q24.13-q24.3 that could potentially be a sparse region of balanced rearrangement breaks. We found that 898 breakpoints caused gene disruption and a total of 188 breakpoints interrupted genes recorded in OMIM. The percentage of breakpoints that disrupted autosomal dominant genes recorded in OMIM was 25.53% (48/188). Fifty-four of the precisely characterized breakpoints had 1-8-bp microhomologous sequences.CONCLUSION:
Our findings provide a reference for the evaluation of the pathogenicity of mutations in related genes that cause protein truncation in clinical practice. According to the characteristics of breakpoints, non-homologous end joining and microhomology-mediated break-induced replication may be the main mechanism for ABCRs formation.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Translocação Genética
/
Aberrações Cromossômicas
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article