title: Screening of deafness-causing DNA variants that are common in patients of European ancestry using a microarray-based approach.
abstract: The unparalleled heterogeneity in genetic causes of hearing loss along with remarkable differences in prevalence of causative variants among ethnic groups makes single gene tests technically inefficient. Although hundreds of genes have been reported to be associated with nonsyndromic hearing loss (NSHL), GJB2, GJB6, SLC26A4, and mitochondrial (mt) MT-RNR1 and MTTS are the major contributors. In order to provide a faster, more comprehensive and cost effective assay, we constructed a DNA fluidic array, CapitalBioMiamiOtoArray, for the detection of sequence variants in five genes that are common in most populations of European descent. They consist of c.35delG, p.W44C, p.L90P, c.167delT (GJB2); 309kb deletion (GJB6); p.L236P, p.T416P (SLC26A4); and m.1555A>G, m.7444G>A (mtDNA). We have validated our hearing loss array by analyzing a total of 160 DNAs samples. Our results show 100% concordance between the fluidic array biochip-based approach and the established Sanger sequencing method, thus proving its robustness and reliability at a relatively low cost.
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, China.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Xiang
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, China.|Tsinghua University School of Medicine, Beijing, China.
authors.forename: Xingping
authors.initials: X
authors.lastname: Chai
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Qing
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Haiqiong
authors.initials: H
authors.lastname: Shang
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Bing
authors.initials: B
authors.lastname: Zou
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mittal
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.|Laboratory for Molecular Medicine, Partners Personalized Medicine, Cambridge, Massachusetts, United States of America.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.|Dr. John T. Macdonald Department of Human Genetics and John P.Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Yao-Shan
authors.initials: YS
authors.lastname: Fan
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.|Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.|Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.|Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.|Division of Evolution and Genomic Science, School of Biological Sciences, Manchester Academic Health Science Center, University of Manchester, United Kingdom.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Morton
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, China.|Tsinghua University School of Medicine, Beijing, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Xing
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, China.|Tsinghua University School of Medicine, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.|Tsinghua University School of Medicine, Beijing, China.|Dr. John T. Macdonald Department of Human Genetics and John P.Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Xue Zhong
authors.initials: XZ
authors.lastname: Liu
mesh_terms: D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003638:Deafness / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D008928:Mitochondria / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters; D044465:White People / Q000235:genetics*
chemical_list: D000075302:Connexin 30; D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26; D004247:DNA