title: Rare A2ML1 variants confer susceptibility to otitis media.
abstract: A duplication variant within the middle ear-specific gene A2ML1 cosegregates with otitis media in an indigenous Filipino pedigree (LOD score = 7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by 3 otitis-prone European-American and Hispanic-American children but is absent in non-otitis-prone children and >62,000 next-generation sequences. We identified seven additional A2ML1 variants in six otitis-prone children. Collectively, our studies support a role for A2ML1 in the pathophysiology of otitis media.
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Regie Lyn P
authors.initials: RL
authors.lastname: Santos-Cortez
authors.affiliation: 1] Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines. [2] Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Chiong
authors.affiliation: 1] Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines. [2] Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Ma Rina T
authors.initials: MR
authors.lastname: Reyes-Quintos
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.
authors.forename: Ma Leah C
authors.initials: ML
authors.lastname: Tantoco
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Anushree
authors.initials: A
authors.lastname: Acharya
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Izoduwa
authors.initials: I
authors.lastname: Abbe
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Arnaud P
authors.initials: AP
authors.lastname: Giese
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: 1] Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia, USA. [2] Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: E Kaitlynn
authors.initials: EK
authors.lastname: Allen
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Biao
authors.initials: B
authors.lastname: Li
authors.affiliation: 1] Institute of Human Genetics, University of the Philippines Manila-National Institutes of Health, Manila, Philippines. [2] Department of Pediatrics, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Cutiongco-de la Paz
authors.affiliation: Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Marieflor Cristy
authors.initials: MC
authors.lastname: Garcia
authors.affiliation: 1] Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines. [2] Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Erasmo Gonzalo D V
authors.initials: EG
authors.lastname: Llanes
authors.affiliation: Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Patrick John
authors.initials: PJ
authors.lastname: Labra
authors.affiliation: 1] Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines. [2] Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Teresa Luisa I
authors.initials: TL
authors.lastname: Gloria-Cruz
authors.affiliation: 1] Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines. [2] Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Abner L
authors.initials: AL
authors.lastname: Chan
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Gao T
authors.initials: GT
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Daly
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bamshad
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.affiliation: Division of Pediatric Infectious Disease and Immunology, Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Janak A
authors.initials: JA
authors.lastname: Patel
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Saima
authors.initials: S
authors.lastname: Riazuddin
authors.affiliation: 1] Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia, USA. [2] Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA. [3] Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Sale
authors.affiliation: Division of Pediatric Infectious Disease and Immunology, Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Tasnee
authors.initials: T
authors.lastname: Chonmaitree
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.affiliation: 1] Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines. [2] Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Generoso T
authors.initials: GT
authors.lastname: Abes
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
mesh_terms: D000818:Animals; D001483:Base Sequence; D002648:Child; D003051:Cochlea / Q000378:metabolism / Q000473:pathology; D059472:Exome / Q000235:genetics; D005192:Family Health; D005260:Female; D020440:Gene Duplication; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D010033:Otitis Media / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D025341:Principal Component Analysis; D011487:Protein Conformation; D017422:Sequence Analysis, DNA; D000511:alpha-Macroglobulins / Q000737:chemistry / Q000235:genetics*
chemical_list: C510358:A2ML1 protein, human; D000511:alpha-Macroglobulins