Cargando…

Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy

Idiopathic superior oblique muscle palsy is a major type of paralytic, non-comitant strabismus and presents vertical and cyclo-torsional deviation of one eye against the other eye, with a large vertical fusion range and abnormal head posture such as head tilt. Genetic background is considered to pla...

Descripción completa

Detalles Bibliográficos
Autores principales: Matsuo, Toshihiko, Chaomulige, Miyaji, Mary, Hosoya, Osamu, Saito, Akira, Nakazono, Kazuyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369257/
https://www.ncbi.nlm.nih.gov/pubmed/35955756
http://dx.doi.org/10.3390/ijms23158626
_version_ 1784766398989336576
author Matsuo, Toshihiko
Chaomulige,
Miyaji, Mary
Hosoya, Osamu
Saito, Akira
Nakazono, Kazuyuki
author_facet Matsuo, Toshihiko
Chaomulige,
Miyaji, Mary
Hosoya, Osamu
Saito, Akira
Nakazono, Kazuyuki
author_sort Matsuo, Toshihiko
collection PubMed
description Idiopathic superior oblique muscle palsy is a major type of paralytic, non-comitant strabismus and presents vertical and cyclo-torsional deviation of one eye against the other eye, with a large vertical fusion range and abnormal head posture such as head tilt. Genetic background is considered to play a role in its development, as patients with idiopathic superior oblique muscle palsy have varying degrees of muscle hypoplasia and, rarely, the complete absence of the muscle, that is, aplasia. In this study, whole genome sequencing was performed, and single nucleotide variations and short insertions/deletions (SNVs/InDels) were annotated in two patients each in three small families (six patients in total) with idiopathic superior oblique muscle palsy, in addition to three normal individuals in one family. At first, linkage analysis was carried out in the three families and SNVs/InDels in chromosomal loci with negative LOD scores were excluded. Next, SNVs/InDels shared by the six patients, but not by the three normal individuals, were chosen. SNVs/InDels were further narrowed down by choosing low-frequency (<1%) or non-registered SNVs/InDels in four databases for the Japanese population, and then by choosing SNVs/InDels with functional influence, leading to one candidate gene, SSTR5-AS1 in chromosome 16. The six patients were heterozygous for 13-nucleotide deletion in SSTR5-AS1, except for one homozygous patient, while the three normal individuals were wild type. Targeted polymerase chain reaction (PCR) and direct sequencing of PCR products confirmed the 13-nucleotide deletion in SSTR5-AS1. In the face of newly-registered SSTR5-AS1 13-nucleotide deletion at a higher frequency in a latest released database for the Japanese population, the skipping of low-frequency and non-registration sorting still resulted in only 13 candidate genes including SSTR5-AS1 as common variants. The skipping of linkage analysis also led to the same set of 13 candidate genes. Different testing strategies that consisted of linkage analysis and simple unintentional bioinformatics could reach candidate genes in three small families with idiopathic superior oblique muscle palsy.
format Online
Article
Text
id pubmed-9369257
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93692572022-08-12 Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy Matsuo, Toshihiko Chaomulige, Miyaji, Mary Hosoya, Osamu Saito, Akira Nakazono, Kazuyuki Int J Mol Sci Article Idiopathic superior oblique muscle palsy is a major type of paralytic, non-comitant strabismus and presents vertical and cyclo-torsional deviation of one eye against the other eye, with a large vertical fusion range and abnormal head posture such as head tilt. Genetic background is considered to play a role in its development, as patients with idiopathic superior oblique muscle palsy have varying degrees of muscle hypoplasia and, rarely, the complete absence of the muscle, that is, aplasia. In this study, whole genome sequencing was performed, and single nucleotide variations and short insertions/deletions (SNVs/InDels) were annotated in two patients each in three small families (six patients in total) with idiopathic superior oblique muscle palsy, in addition to three normal individuals in one family. At first, linkage analysis was carried out in the three families and SNVs/InDels in chromosomal loci with negative LOD scores were excluded. Next, SNVs/InDels shared by the six patients, but not by the three normal individuals, were chosen. SNVs/InDels were further narrowed down by choosing low-frequency (<1%) or non-registered SNVs/InDels in four databases for the Japanese population, and then by choosing SNVs/InDels with functional influence, leading to one candidate gene, SSTR5-AS1 in chromosome 16. The six patients were heterozygous for 13-nucleotide deletion in SSTR5-AS1, except for one homozygous patient, while the three normal individuals were wild type. Targeted polymerase chain reaction (PCR) and direct sequencing of PCR products confirmed the 13-nucleotide deletion in SSTR5-AS1. In the face of newly-registered SSTR5-AS1 13-nucleotide deletion at a higher frequency in a latest released database for the Japanese population, the skipping of low-frequency and non-registration sorting still resulted in only 13 candidate genes including SSTR5-AS1 as common variants. The skipping of linkage analysis also led to the same set of 13 candidate genes. Different testing strategies that consisted of linkage analysis and simple unintentional bioinformatics could reach candidate genes in three small families with idiopathic superior oblique muscle palsy. MDPI 2022-08-03 /pmc/articles/PMC9369257/ /pubmed/35955756 http://dx.doi.org/10.3390/ijms23158626 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Matsuo, Toshihiko
Chaomulige,
Miyaji, Mary
Hosoya, Osamu
Saito, Akira
Nakazono, Kazuyuki
Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy
title Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy
title_full Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy
title_fullStr Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy
title_full_unstemmed Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy
title_short Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy
title_sort candidate genes in testing strategies for linkage analysis and bioinformatic sorting of whole genome sequencing data in three small japanese families with idiopathic superior oblique muscle palsy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369257/
https://www.ncbi.nlm.nih.gov/pubmed/35955756
http://dx.doi.org/10.3390/ijms23158626
work_keys_str_mv AT matsuotoshihiko candidategenesintestingstrategiesforlinkageanalysisandbioinformaticsortingofwholegenomesequencingdatainthreesmalljapanesefamilieswithidiopathicsuperiorobliquemusclepalsy
AT chaomulige candidategenesintestingstrategiesforlinkageanalysisandbioinformaticsortingofwholegenomesequencingdatainthreesmalljapanesefamilieswithidiopathicsuperiorobliquemusclepalsy
AT miyajimary candidategenesintestingstrategiesforlinkageanalysisandbioinformaticsortingofwholegenomesequencingdatainthreesmalljapanesefamilieswithidiopathicsuperiorobliquemusclepalsy
AT hosoyaosamu candidategenesintestingstrategiesforlinkageanalysisandbioinformaticsortingofwholegenomesequencingdatainthreesmalljapanesefamilieswithidiopathicsuperiorobliquemusclepalsy
AT saitoakira candidategenesintestingstrategiesforlinkageanalysisandbioinformaticsortingofwholegenomesequencingdatainthreesmalljapanesefamilieswithidiopathicsuperiorobliquemusclepalsy
AT nakazonokazuyuki candidategenesintestingstrategiesforlinkageanalysisandbioinformaticsortingofwholegenomesequencingdatainthreesmalljapanesefamilieswithidiopathicsuperiorobliquemusclepalsy