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1.  Evolutionarily Assembled cis-Regulatory Module at a Human Ciliopathy Locus 
Science (New York, N.Y.)  2012;335(6071):966-969.
Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.
doi:10.1126/science.1213506
PMCID: PMC3671610  PMID: 22282472
2.  The ciliopathies: A transitional model into systems biology of human genetic disease 
The last decade has witnessed an explosion in the identification of genes, mutations in which appear sufficient to cause clinical phenotypes in humans. This is especially true for disorders of ciliary dysfunction in which an excess of 50 causal loci are now known; this discovery was driven in part by an improved understanding of the protein composition of the cilium and the co-occurrence of clinical phenotypes associated with ciliary dysfunction. Despite this progress, the fundamental challenge of predicting phenotype and or clinical progression based on single locus information remains unsolved. Here, we explore how the combinatorial knowledge of allele quality and quantity, an improved understanding of the biological composition of the primary cilium, and the expanded appreciation of the subcellular roles of this organelle can be synthesized to generate improved models that can explain both causality but also variable penetrance and expressivity.
doi:10.1016/j.gde.2012.04.006
PMCID: PMC3509787  PMID: 22632799
3.  Differentiating Central Centrifugal Cicatricial Alopecia and Androgenetic Alopecia in African American Men 
Central centrifugal cicatricial alopecia is a scarring alopecia that is predominantly seen in African American women, but occurs less frequently in men. The authors present three cases of African American men with biopsy-proven central centrifugal cicatricial alopecia and detail the clinical presentation, histological findings, and treatment regimens. Central centrifugal cicatricial alopecia should be considered in the differential diagnosis when evaluating male patients with vertex hair loss accompanied by scalp symptoms. Physicians should maintain a high index of suspicion in African American men with the appropriate clinical picture and confirm the diagnosis by scalp biopsy. Prompt and appropriate treatment can help halt or slow disease progression.
PMCID: PMC3390231  PMID: 22768355

Results 1-3 (3)