PolyG (Polyglycine) Repeat and Human Diseases: An Update on the Biology, Diseases Mechanisms and Current Therapeutic Interventions
B. R. Mahalakshmi
*
Department of Zoology and Genetics, Government Science College, Nrupathunga University, Nrupathunga Road, Bangalore-560001, Karnataka, India.
J. N. Sharada Devi
Department of Zoology and Genetics, Government Science College, Nrupathunga University, Nrupathunga Road, Bangalore-560001, Karnataka, India.
D. J. Shruthi
Department of Zoology, Yuvaraja’s College, Mysuru, Karnataka, India.
B. K. Manjunath
Department of Biotechnology, Oxford College of Engineering, Bengaluru, Karnataka, India.
H. B. Kiran Kumar
Government Science College, Nrupathunga University, Nrupathunga Road, Bangalore-560001, Karnataka, India.
*Author to whom correspondence should be addressed.
Abstract
Nucleotide repeats known as short tandem repeats (STRs) can be found in both coding and non-coding areas of the human genome such a polyglutamine (polyQ), polyglycine (polyG) and polyalanine (PolyA). PolyG repeat expansions, are caused by GGC repeat expansions leading to numerous neurodegenerative illnesses, including as myotonic dystrophies (DM1 and DM2), Fragile X-associated tremor/ataxia syndrome (FXTAS), and some Spinocerebellar ataxias (SCAs). They are also linked to other organ ailments that representing the wider range of diseases. The central and peripheral neurological systems as well as the muscular system are the main organs affected by the polyG diseases, which are adult-onset, slowly progressing, multi-system neurodegenerative disorders. Given the significance of polyG diseases and existing knowledge gaps, the goal of present review is to update the current knowledge and understanding of polyG illnesses. Since this class of repeat induced human diseases have received less attention in comparison to other triplet repeats expansion diseases. Using published literature from public databases, thesis and journals we provide a back ground to the basics of STR distribution and their role in the human genome. The impact of STR repeat on the transcription and translation forms the second chapter. The central part of the review is focussed on pathology, biology and markers of the disorders. The impact of these repeats on human multi-organ diseases is covered in two sections. Finally, the current therapeutic applications to treat these diseases provide an update on the current methods. With the advancements in next-generation sequencing technology several polyG disorders and their causative genes are being discovered at higher pace. An update of the current knowledge will provide newer objectives and aims for research on the illnesses thus enabling identification of genes and new potent targets of the polyG protein. Further, it is envisaged that it will provide better diagnosis, intervention and treatment options.
Keywords: Short tandem repeats (STRs), fragile x-associated tremor/ataxia syndrome (FXTAS), polyG disorders, neuronal intranuclear inclusion disease (NIID), oculopharyngodistal myopathy (OPDM)