An ancient founder mutation located between ROBO1 and ROBO2 is responsible for increased microtia risk in Amerindigenous populations

Daniel Quiat, Seong Won Kim, Qi Zhang, Sarah U. Morton, Alexandre C. Pereira, Steven R. DePalma, Jon A.L. Willcox, Barbara McDonough, Daniel M. DeLaughter, Joshua M. Gorham, Justin J. Curran, Melissa Tumblin, Yamileth Nicolau, Maria A. Artunduaga, Lourdes Quintanilla-Dieck, Gabriel Osorno, Luis Serrano, Usama Hamdan, Roland D. Eavey, Christine E. SeidmanJ. G. Seidman

Research output: Contribution to journalArticlepeer-review

Abstract

SignificanceThe genetic basis of isolated microtia, a congenital abnormality of the external ear, is poorly understood. Indigenous American (Amerindigenous) populations have the highest reported incidence of microtia. Here, we use whole genome sequencing to study microtia in Latin American families and identify a common microtia risk allele that is enriched among individuals with Amerindigenous ancestry. This allele is located in a regulatory region governing the expression of Roundabout 1 (ROBO1) and Roundabout 2 (ROBO2) in induced pluripotent stem cell-derived neural crest cells and is associated with a complex repeat sequence. These results identify a shared genetic basis for isolated microtia and other craniofacial abnormalities and account for, at least in part, the increased incidence of microtia in Amerindigenous populations.

Original languageEnglish (US)
Pages (from-to)e2203928119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number21
DOIs
StatePublished - May 24 2022

Keywords

  • ancestry
  • craniofacial microsomia
  • microtia

ASJC Scopus subject areas

  • General

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