The position of the longest intron is related to biological functions in some human genes

Dvořák, Pavel; Hanicinec, Vojtech; Souček, Pavel

doi:10.3389/fgene.2022.1085139

Cited by 3 publications

(4 citation statements)

References 29 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The insertion falls between coding exons of PITX2 isoforms PITX2A and B but is upstream of PITX2C. For transcripts PITX2A and B, this rearrangement results in the insertion of coding regions for other genes within intron 2/3 and extends the size of the intron by more than 50Â, from $11,000 bp to more than 612,000 bp, which is well outside the described human intron size range (Dvorak et al, 2023). Both the excessive size of the derivative intron and the inclusion of coding regions from other genes makes it unlikely that proper splicing will occur for the PITX2A/B transcripts.…”

Section: Predicted Effectmentioning

confidence: 94%

Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld‐Rieger Syndrome

Farris,

Khanna,

Smadbeck

et al. 2024

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Axenfeld‐Rieger Syndrome (ARS) type 1 is a rare autosomal dominant condition characterized by anterior chamber anomalies, umbilical defects, dental hypoplasia, and craniofacial anomalies, with Meckel's diverticulum in some individuals. Here, we describe a clinically ascertained female of childbearing age with ARS for whom clinical targeted sequencing and deletion/duplication analysis followed by clinical exome and genome sequencing resulted in no pathogenic variants or variants of unknown significance in PITX2 or FOXC1. Advanced bioinformatic analysis of the genome data identified a complex, balanced rearrangement disrupting PITX2. This case is the first reported intrachromosomal rearrangement leading to ARS, illustrating that for patients with compelling clinical phenotypes but negative genomic testing, additional bioinformatic analysis are essential to identify subtle genomic abnormalities in target genes.

show abstract

Section: Predicted Effectmentioning

confidence: 94%

Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld‐Rieger Syndrome

Farris,

Khanna,

Smadbeck

et al. 2024

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Based on our previous work with the human genome and the knowledge that the distribution of the positions of the longest introns showed three peaks—at the beginning, middle and end of the gene, we divided all protein-coding genes of the studied organism into those containing less than three introns and which contain three or more introns [ 17 ]. We further divided genes with three or more introns into three subgroups according to the relative position of the longest intron (defined above).…”

Section: Methodsmentioning

confidence: 99%

“…In our initial work on a selection of protein-coding genes of the human genome, we showed that approximately 64% of the genes have the longest intron in the 1 st tertile of all introns in the gene, while 19% in the second and 17% in the third. Notable peaks were seen at the position in the middle of the gene and the last intron (5 and 6%, respectively) [ 17 ]. It was therefore clear that a non-negligible number of genes do not have the longest introns in the first positions.…”

Section: Introductionmentioning

confidence: 99%

Genes divided according to the relative position of the longest intron show increased representation in different KEGG pathways

Dvorak,

Hlavac,

Hanicinec

et al. 2024

BMC Genomics

Self Cite

View full text Add to dashboard Cite

Despite the fact that introns mean an energy and time burden for eukaryotic cells, they play an irreplaceable role in the diversification and regulation of protein production. As a common feature of eukaryotic genomes, it has been reported that in protein-coding genes, the longest intron is usually one of the first introns. The goal of our work was to find a possible difference in the biological function of genes that fulfill this common feature compared to genes that do not. Data on the lengths of all introns in genes were extracted from the genomes of six vertebrates (human, mouse, koala, chicken, zebrafish and fugu) and two other model organisms (nematode worm and arabidopsis). We showed that more than 40% of protein-coding genes have the relative position of the longest intron located in the second or third tertile of all introns. Genes divided according to the relative position of the longest intron were found to be significantly increased in different KEGG pathways. Genes with the longest intron in the first tertile predominate in a range of pathways for amino acid and lipid metabolism, various signaling, cell junctions or ABC transporters. Genes with the longest intron in the second or third tertile show increased representation in pathways associated with the formation and function of the spliceosome and ribosomes. In the two groups of genes defined in this way, we further demonstrated the difference in the length of the longest introns and the distribution of their absolute positions. We also pointed out other characteristics, namely the positive correlation between the length of the longest intron and the sum of the lengths of all other introns in the gene and the preservation of the exact same absolute and relative position of the longest intron between orthologous genes.

show abstract

“…In our first study on this topic, we further defined the distribution of the longest introns in human genes - 64% of genes with the longest intron in the first third of all introns and 19 and 17% for the second and third third, with notable peaks for the middle and last introns of approx. 5 and 6%, respectively [6]. Moreover, we showed that localization of the longest intron in the second or third third is significantly more frequent for certain functionally related groups of genes, e.g.…”

Section: Introductionmentioning

confidence: 99%

The longest intron rule

Dvorak,

Hlavac,

Hanicinec

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Despite the fact that long introns mean an energy and time burden for eukaryotic cells, they play an irreplaceable role in the diversification and regulation of protein production. A general feature is the accumulation of the longest introns closer to the start of protein-coding genes. Our work aimed to more closely characterize the genes in which the longest intron is only located in the second or third third of the gene. Data on the lengths of all introns in genes were extracted from the genomes of 4 vertebrates (human, mouse, chicken and zebrafish), nematode worm and yeast. With the genes divided according to the relative position of the longest intron, gene set enrichment analyses were performed, the results of which were then confronted with the results of randomly generated gene sets of the same size. The analyses show that among the genes associated with biological processes of ion transport across membranes, cell signaling or the development of multicellular organisms, there is a greater representation of genes with the longest intron in the first third. Conversely, among the genes associated with the processes of RNA processing and ribosome biogenesis, there are more genes with the longest intron in the second or third third. It is a newly discovered characteristic with more general validity among multicellular organisms.

show abstract

The position of the longest intron is related to biological functions in some human genes

Cited by 3 publications

References 29 publications

Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld‐Rieger Syndrome

Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld‐Rieger Syndrome

Genes divided according to the relative position of the longest intron show increased representation in different KEGG pathways

The longest intron rule

Contact Info

Product

Resources

About