Whole-Exome Sequencing of Discordant Monozygotic Twin Families for Identification of Candidate Genes for Microtia-Atresia

Frontiers in Genetics
Xinmiao FanXiaowei Chen

Abstract

We used data from twins and their families to probe the genetic factors contributing to microtia-atresia, in particular, early post-twinning variations that potentially account for the discordant phenotypes of monozygotic twin pairs. Six families of monozygotic twins discordant for congenital microtia-atresia were recruited for study. The six patients shared a consistent clinical phenotype of unilateral microtia-atresia. Whole-exome sequencing (WES) was performed for all six twin pairs and their parents. Family segregation and multiple bioinformatics methods were applied to identify suspicious mutations in all families. Recurring mutations commonly detected in at least two families were highlighted. All variants were validated via Sanger sequencing. Gene Ontology (GO) analysis was performed to identify candidate gene sets and related pathways. Copy number variation (CNV), linkage analysis, association analysis and machine learning methods were additionally applied to isolate candidate mutations, and comparative genomics and structural modeling tools used to evaluate their potential roles in onset of microtia-atresia. Our analyses revealed 61 genes with suspected mutations associated with microtia-atresia. Five (HOXA4, MUC6, CHS...Continue Reading

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Citations

Jun 28, 2021·Orphanet Journal of Rare Diseases·Ewelina Bukowska-OlechAleksander Jamsheer

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Datasets Mentioned

BETA
PRJNA665131

Methods Mentioned

BETA
electrophoresis
PCR
Exome Sequencing

Software Mentioned

CNVkit
SPSS
Exome Aggregation Consortium ( ExAC ) Browser
Human Splicing Finder
Sequencing Analysis
Illumina
SWISS
Polyphen
CADD
MODEL

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