In the era of Big Data, obtaining a huge amount of information is the easy part; knowing what to do with it is another story entirely. But now, researchers have reported that a new approach to analyzing data from genome-wide association studies could help uncover the genetic basis of many diseases.
In a study published in in Nature Communications, researchers have revealed that analyzing the coding sequences of gene splicing variants at sites associated with disease can help reveal the genetic cause of certain complex human diseases.
Variations in our genes cause complex diseases, but it can be difficult to tell how a single genetic variation leads to disease. While some variants cause disease by changing gene expression levels, it is increasingly apparent that splicing variants that affect how a gene is transcribed – meaning, how a gene’s DNA sequence is copied into RNA - also play an important role.
“There are a number of existing approaches to identify and analyze genetic variants causing splicing changes in disease-associated genes,” explains the, lead author on the study. “However, these approaches are limited by incomplete annotation of splicing isoforms and by the use of the same splicing junction by multiple isoforms, which can make them difficult to distinguish from each other.”
To overcome these drawbacks, the researchers developed a set of two analyses that more fully capture the complexity of splicing variations and their relationship to human disease: the first analysis integrates isoforms with the same coding sequence to detect resulting changes in protein structure, and the second analysis examines the effects of isoforms with incomplete annotations but unique coding sequences. The team then determined the complete sequences of these isoforms and validated their expression in cells.
“The results showed that our approach is both robust and effective,” states the senior author on the paper. “We successfully identified 29 full-length isoforms with unannotated coding sequences associated with genetic variants that have been linked to diseases such as Parkinson’s disease, ankylosing spondylitis, irritable bowel disease, and neurodegenerative disease.”
Furthermore, they showed that genes with disease-associated splicing variants can be identified by evaluating their effects on the expression of other genes within the genome. For example, a variant leading to alteration in the ratio of two isoforms of the SNRPC gene was identified as being associated with systemic lupus erythematosus.
Taken together, these findings highlight the unappreciated role of protein-altering splicing variants in causing disease. Identifying relevant variants and assessing their function in future research using animal models could help clarify how complex diseases arise.
https://www.nature.com/articles/s41467-022-32358-1
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fsplicing-qtl-analysis&filter=22
A new data analysis approach identifies disease-associated splicing variants
- 1,173 views
- Added
Latest News
Protein that helps COVID-19…
By newseditor
Posted 26 Jul
Spinal Muscular Atrophy (SM…
By newseditor
Posted 26 Jul
Link between bowel movement…
By newseditor
Posted 26 Jul
Inhibition of IL-11 signall…
By newseditor
Posted 25 Jul
Brain changes linked to obe…
By newseditor
Posted 25 Jul
Other Top Stories
'Natural killer' cells could halt Parkinson's progression
Read more
How inflammation triggers fatal cycle in Alzheimer's disease
Read more
A protein controls inflammation through non-enzymatic activities
Read more
Sex-specific traits of the immune system explain men's susceptibili…
Read more
Too much salt weakens the immune system and may increase infections
Read more
Protocols
A systems biology approach…
By newseditor
Posted 24 Jul
quantms: a cloud-based pipe…
By newseditor
Posted 22 Jul
Emerging tools and best pra…
By newseditor
Posted 19 Jul
Directly selecting cell-typ…
By newseditor
Posted 17 Jul
PUFFFIN: an ultra-bright, c…
By newseditor
Posted 16 Jul
Publications
Hepatocyte-intrinsic SMN de…
By newseditor
Posted 26 Jul
Aberrant bowel movement fre…
By newseditor
Posted 26 Jul
A pseudoautosomal glycosyla…
By newseditor
Posted 26 Jul
Microglia protect against a…
By newseditor
Posted 26 Jul
Rigor and reproducibility i…
By newseditor
Posted 26 Jul
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar