[Genetic complexity of ciliopathies and novel genes identification].
Ciliopathies are a large group of human disorders caused by dysfunction of primary or motile cilia and unified by their overlapping clinical features (brain malformations, retinal dystrophy, cystic kidney disease, liver fibrosis and skeletal abnormalities). Ciliopathies are mendelian disorders with prominent genetic heterogeneity and marked allelism between different clinical entities, which are in part explained by the recently identified functional modules and multi-protein complexes formed by ciliopathy-associated gene products. The current review provides an updated snapshot of this complex evolving field, highlighting the key phenotypic features and causative genes for commonly-studied ciliopathies and summarizing our emerging understanding of the correlations between the functions of subgroups of genes and clinical sub-types of ciliopathies. Using the example of Joubert syndrome, a ciliopathy characterized by a distinctive hindbrain malformation and caused by mutations in more than 20 different genes, this work also reviews the principal methods used for new gene identification, including candidate gene approaches, homozygosity mapping as well as high throughput next-generation and exome sequencing.
Institut moléculaire des sciences de la vie, Institut de médecine génétique, université de Zurich, Winterthurerstrasse 190, 8057 Zurich, Suisse.
Ruxandra
R
Bachmann-Gagescu
D000015:Abnormalities, Multiple; D000818:Animals; D016764:Cell Polarity; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities; D002874:Chromosome Mapping; D002923:Cilia / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D002925:Ciliary Motility Disorders / Q000145:classification / Q000235:genetics*; D004195:Disease Models, Animal; D005124:Eye Abnormalities / Q000235:genetics / Q000473:pathology; D005544:Forecasting; D005808:Genes, Recessive; D056726:Genetic Association Studies; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000473:pathology; D018740:Genetic Heterogeneity; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008868:Microtubule Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020409:Molecular Motor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040901:Proteomics; D012160:Retina / Q000002:abnormalities / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods; D013577:Syndrome; D049490:Systems Biology / Q000379:methods
D008565:Membrane Proteins; D008868:Microtubule Proteins; D020409:Molecular Motor Proteins