Study of the molecular cause of anophthalmia in a consanguineous pedigree

• Author / Creator

  Khorshidi, Azam

• Anophthalmia is a genetically heterogeneous congenital disorder. By using homozygosity mapping in six individuals with anophthalmia from a consanguineous family, five homozygous regions more than one megabase (Mb) in size were identified, which together encompassed 18 Mb. Sequencing of high-priority candidate genes failed to identify the causative mutation. Alternatively, whole exome sequencing of one affected individual revealed a homozygous missense mutation (c.39T>A [p.Ala13Val]) in TNIP3, located on homozygous interval on chromosome 4q26-28.1. This mutation was not present in 140 control individuals, single-nucleotide polymorphism databases, or the 1000 Genomes database. There were also several other potential variants elsewhere in the genome which their pathogenesity could not be ruled out, indicating that in heterogeneous diseases a single exome sequencing data is not enough to isolate the pathogenic variant with high confidence. Exome sequencing of more individuals in this family hold the promise to identify mutant gene responsible for the anophthalmia phenotype.

• Subjects / Keywords

  • Next-generation sequencing
  • Anophthalmia
  • Copy number variation
  • Homozygosity mapping

• Graduation date

  Fall 2012

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3V311

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.