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ID 63044
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Zhang, Jingjing Regenerative and Reconstructive Medicine (Ophthalmology), Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Matsuo, Toshihiko Regenerative and Reconstructive Medicine (Ophthalmology), Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Hamasaki, Ichiro Department of Ophthalmology, Okayama University Hospital Kaken ID
Sato, Kazuhiro Barley and Wild Plant Resource Center, Institute of Plant Science and Resources (IPSR), Okayama University
Abstract
Background: Esotropia and exotropia are two major phenotypes of comitant strabismus. It remains controversial whether esotropia and exotropia would share common genetic backgrounds. In this study, we used a quantitative trait locus (QTL)-sequencing pipeline for diploid plants to screen for susceptibility loci of strabismus in whole exome sequencing of pooled genomic DNAs of individuals. Methods: Pooled genomic DNA (2.5 ng each) of 20 individuals in three groups, Japanese patients with esotropia and exotropia, and normal members in the families, was sequenced twice after exome capture, and the first and second sets of data in each group were combined to increase the read depth. The SNP index, as the ratio of variant genotype reads to all reads, and Δ(SNP index) values, as the difference of SNP index between two groups, were calculated by sliding window analysis with a 4 Mb window size and 10 kb slide size. The rows of 200 “N”s were inserted as a putative 200-b spacer between every adjoining locus to depict Δ(SNP index) plots on each chromosome. SNP positions with depth < 20 as well as SNP positions with SNP index of <0.3 were excluded. Results: After the exclusion of SNPs, 12,242 SNPs in esotropia/normal group and 12,108 SNPs in exotropia/normal group remained. The patterns of the Δ(SNP index) plots on each chromosome appeared different between esotropia/normal group and exotropia/normal group. When the consecutive groups of SNPs on each chromosome were set at three patterns: SNPs in each cytogenetic band, 50 consecutive sliding SNPs, and SNPs in 4 Mb window size with 10 kb slide size, p values (Wilcoxon signed rank test) and Q values (false discovery rate) in a few loci as Manhattan plots showed significant differences in comparison between the Δ(SNP index) in the esotropia/normal group and exotropia/normal group. Conclusions: The pooled DNA sequencing and QTL mapping approach for plants could provide overview of genetic background on each chromosome and would suggest different genetic backgrounds for two major phenotypes of comitant strabismus, esotropia and exotropia.
Keywords
strabismus
esotropia
exotropia
diploid plant
human
quantitative trait locus (QTL)
pooled genomic DNA
chromosome
single nucleotide polymorphism (SNP)
whole exome sequencing
Published Date
2021-12-27
Publication Title
Life
Volume
volume12
Issue
issue1
Publisher
MDPI AG
Start Page
41
ISSN
2075-1729
Content Type
Journal Article
language
English
OAI-PMH Set
岡山大学
Copyright Holders
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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publisher
DOI
Related Url
isVersionOf https://doi.org/10.3390/life12010041
License
https://creativecommons.org/licenses/by/4.0/
Citation
Zhang, J.; Matsuo, T.; Hamasaki, I.; Sato, K. Whole Exome-Sequencing of Pooled Genomic DNA Samples to Detect Quantitative Trait Loci in Esotropia and Exotropia of Strabismus in Japanese. Life 2022, 12, 41. https://doi.org/10.3390/ life12010041