Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage ana...

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Autores principales:	Xin Li, Jintian Hu, Jiao Zhang, Qian Jin, Duen-Mei Wang, Jun Yu, Qingguo Zhang, Yong-Biao Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/411b3943b8344c5f821dc543fbf01005
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spelling	oai:doaj.org-article:411b3943b8344c5f821dc543fbf010052021-11-25T06:10:05ZGenome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.1932-620310.1371/journal.pone.0101152https://doaj.org/article/411b3943b8344c5f821dc543fbf010052014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24983964/?tool=EBIhttps://doaj.org/toc/1932-6203Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32-4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean) of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively). Haplotype reconstruction analysis of the 4p15.32-4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65-30.24 cM; 5.54-15.58 Mb). Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.Xin LiJintian HuJiao ZhangQian JinDuen-Mei WangJun YuQingguo ZhangYong-Biao ZhangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e101152 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xin Li Jintian Hu Jiao Zhang Qian Jin Duen-Mei Wang Jun Yu Qingguo Zhang Yong-Biao Zhang Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.
description	Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32-4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean) of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively). Haplotype reconstruction analysis of the 4p15.32-4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65-30.24 cM; 5.54-15.58 Mb). Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.
format	article
author	Xin Li Jintian Hu Jiao Zhang Qian Jin Duen-Mei Wang Jun Yu Qingguo Zhang Yong-Biao Zhang
author_facet	Xin Li Jintian Hu Jiao Zhang Qian Jin Duen-Mei Wang Jun Yu Qingguo Zhang Yong-Biao Zhang
author_sort	Xin Li
title	Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.
title_short	Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.
title_full	Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.
title_fullStr	Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.
title_full_unstemmed	Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.
title_sort	genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/411b3943b8344c5f821dc543fbf01005
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_version_	1718414095993012224

Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

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