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Contribution of rare and common variants determine complex diseases-Hirschsprung disease as a model

Authors
  • Alves, Maria M.
  • Sribudiani, Yunia
  • Brouwer, Rutger W.W.
  • Amiel, Jeanne
  • Antiñolo, Guillermo
  • Borrego, Salud
  • Ceccherini, Isabella
  • Chakravarti, Aravinda
  • Fernández, Raquel M.
  • Garcia-Barcelo, Maria-Mercè
  • Griseri, Paola
  • Stanislas Lyonnet
  • Tam, Paul K.
  • van IJcken, Wilfred F.J.
  • Eggen, Bart J.L.
  • te Meerman, Gerard J.
  • Hofstra, Robert M.W.
Type
Published Article
Journal
Developmental Biology
Publisher
Elsevier BV
Publication Date
Jul 02, 2013
Volume
382
Issue
1
Pages
9–320
Identifiers
DOI: 10.1016/j.ydbio.2013.05.019
PMID: 23707863
Source
USPC - SET - SVS
License
Green

Abstract

Finding genes for complex diseases has been the goal of many genetic studies. Most of these studies have been successful by searching for genes and mutations in rare familial cases, by screening candidate genes and by performing genome wide association studies. However, only a small fraction of the total genetic risk for these complex genetic diseases can be explained by the identified mutations and associated genetic loci. In this review we focus on Hirschsprung disease (HSCR) as an example of a complex genetic disorder. We describe the genes identified in this congenital malformation and postulate that both common 'low penetrant' variants in combination with rare or private 'high penetrant' variants determine the risk on HSCR, and likely, on other complex diseases. We also discuss how new technological advances can be used to gain further insights in the genetic background of complex diseases. Finally, we outline a few steps to develop functional assays in order to determine the involvement of these variants in disease development.

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