A surprising abundance of human disease genes in a simple “basal” animal, the starlet sea anemone (Nematostella vectensis)

Invertebrate animals have provided important insights into the mechanisms of, and treatment for, numerous human diseases. A surprisingly high proportion of genes underlying human disease are present in the genome of a simple, evolutionarily basal invertebrate animal, Nematostella vectensis , including some genes that are absent in established invertebrate model organisms. This, together with the laboratory tractability and regenerative capability of N. vectensis, recommends the species as an important new experimental model for the study of genes underlying human disease.

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COMPARATIVE ANALYSIS OF DISEASE-ASSOCIATED MUTATIONS IN THE CODING REGIONS OF ALTERNATIVELY AND CONSTITUTIVELY SPLICED HUMAN GENES

Journal of Biological System ◽

10.1142/s0218339008002563 ◽

2008 ◽

Vol 16 (02) ◽

pp. 241-253

Author(s):

QIANLI HUANG ◽

YONG LI ◽

JESSE LI-LING ◽

HUIFANG HUANG ◽

XUEPING CHEN ◽

...

Keyword(s):

Alternative Splicing ◽

Codon Usage ◽

Codon Usage Bias ◽

Human Disease ◽

Molecular Mechanisms ◽

Human Diseases ◽

Disease Genes ◽

Single Mutation ◽

Coding Regions ◽

Human Disease Genes

To better understand the evolutionary and molecular mechanisms of alternative splicing causing human diseases, we have systematically compared the pattern, the distribution and the density of disease-associated mutations as well as the influence of codon usage bias on the single mutation between alternatively and constitutively spliced genes through analysis of the large datasets from human disease genes. The results indicated that: 1. The most common pattern of single mutation in alternatively and constitutively spliced genes are, respectively, C/T (25.17%), (22.81%) and G/A (21.54%), (22.73%), suggesting that the two types of disease genes are prone to C → T and G → A mutations. 2. There is an overall preponderance for transitions over transversions in alternatively (62.88% versus 37.12%) and constitutively (64.41% versus 35.59%) spliced disease genes. 3. For the second base of codons, there exist significant differences in transitions and transversions between the two types of genes. 4. Our data indicated that the single mutation tends to occur preferentially when the upstream neighboring-nucleotide is C or G in human disease genes. 5. Codon usage bias and synonymous codon usage have great influence on the single mutation in both alternatively and constitutively spliced genes. The GC content and gene length also have very evident influence on such mutations. Our results seem to imply that disease-associated mutations within the coding regions of alternatively spliced human disease genes have different mechanisms from constitutively spliced genes. Such findings may facilitate understanding the molecular mechanism of alternative splicing causing human diseases, and the development of gene therapies for such diseases.

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A liquid-like organelle at the root of motile ciliopathy

eLife ◽

10.7554/elife.38497 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 23

Author(s):

Ryan L Huizar ◽

Chanjae Lee ◽

Alexander A Boulgakov ◽

Amjad Horani ◽

Fan Tu ◽

...

Keyword(s):

Phase Separation ◽

Ectopic Pregnancy ◽

Human Disease ◽

Airway Disease ◽

Stress Granule ◽

Human Diseases ◽

Disease Genes ◽

Multiciliated Cells ◽

Chronic Airway Disease ◽

Human Disease Genes

Motile ciliopathies are characterized by specific defects in cilia beating that result in chronic airway disease, subfertility, ectopic pregnancy, and hydrocephalus. While many patients harbor mutations in the dynein motors that drive cilia beating, the disease also results from mutations in so-called dynein axonemal assembly factors (DNAAFs) that act in the cytoplasm. The mechanisms of DNAAF action remain poorly defined. Here, we show that DNAAFs concentrate together with axonemal dyneins and chaperones into organelles that form specifically in multiciliated cells, which we term DynAPs, for dynein axonemal particles. These organelles display hallmarks of biomolecular condensates, and remarkably, DynAPs are enriched for the stress granule protein G3bp1, but not for other stress granule proteins or P-body proteins. Finally, we show that both the formation and the liquid-like behaviors of DynAPs are disrupted in a model of motile ciliopathy. These findings provide a unifying cell biological framework for a poorly understood class of human disease genes and add motile ciliopathy to the growing roster of human diseases associated with disrupted biological phase separation.

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