The intron has been a big biological mystery since it was first discovered in several aspects. First, all of the completely sequenced eukaryotes harbor introns in the genomic structure, whereas no prokaryotes identified so far carry introns. Second, the amount of total introns varies in different species. Third, the length and number of introns vary in different genes, even within the same species genome. Fourth, all introns are copied into RNAs by transcription and DNAs by replication processes, but intron sequences do not participate in protein-coding sequences. The existence of introns in the genome should be a burden to some cells, because cells have to consume a great deal of energy to copy and excise them exactly at the correct positions with the help of complicated spliceosomal machineries. The existence throughout the long evolutionary history is explained, only if selective advantages of carrying introns are assumed to be given to cells to overcome the negative effect of introns. In that regard, we summarize previous research about the functional roles or benefits of introns. Additionally, several other studies strongly suggesting that introns should not be junk will be introduced.
DNA ; Eukaryota ; Genome* ; Introns* ; RNA

OBJECTIVETo study the human dystrophin gene molecular deletion mechanism, we analyzed breakpoint regions within junction fragments of deletion-type patients and investigated whether the dystrophin gene's intron structure might be related to intron instability.

METHODSJunction fragments corresponding to exon 46 and 51 deletions were cloned. The breakpoint regions were sequenced, and the features of introns with available Genebank sequences were analyzed.

RESULTSAn analysis of junction fragment sequences corresponding to exon 46 and 51 deletions showed that all 5' and 3' breakpoints are located within repeat sequences. No small insertions, small deletions, or point mutations are located near the breakpoint junctions. By analyzing the secondary structure of the junction fragments, we demonstrated that all junction fragment breakpoints are located in non-matching regions of single-stranded hairpin loops. A high concentration of repetitive elements is found to be a key feature of many dystrophin introns. In total, 34.8% of the overall dystrophin intron sequences is composed of repeat sequences.

CONCLUSIONRepeat elements in many dystrophin gene introns are the key to their structural bases and reflect intron instability. As a result of the primary DNA sequences, single-stranded hairpin loops form, increasing the instability of the gene, and forming the base for breaks in the DNA. The formation of the single-stranded hairpins can result in reattachment of two different breakpoints, producing a deletion.

No abstract available.
Introns* ; Point Mutation* ; Protein-Tyrosine Kinases* ; Tyrosine*

Episodic ataxia type 2 (EA-2) is an inherited disorder that is characterized by intermittent vertigo, ataxia, and interictal gaze-evoked nystagmus. Although abnormalities associated with this disorder have been found in the CACNA1A gene encoding the alpha1A (Cav2.1) subunit of the P/Q-type calcium channel, there are few reports of genetically confirmed EA-2 in Korea. In 1998, a Korean family with acetazolamide-responsive hereditary paroxysmal ataxia was reported, but the genetic background was not defined at that time. In the present study we performed direct sequencing of the entire exons and their flanking intronic sequences of the CACNA1A gene and found a deletion mutation (c.2042_2043delAG).
Ataxia* ; Calcium Channels ; Exons ; Humans ; Introns ; Korea ; Sequence Deletion* ; Vertigo

OBJECTIVE: To explore the association of the CYP19 gene polymorphism with the risk of endometriosis. METHODS: Two hundred seventy-nine women with surgically or histologically diagnosed endometriosis of stages I-IV (ASRM, 1997) were recruited, and two hundred eighteen patients with no evidence of endometriosis by laparoscopy or laparotomy served as control. We analysed the frequency and distribution of a TTTA repeat polymorphism and a 3 bp insertion (I)/deletion (D) polymorphism in intron 4 of the CYP19 gene. RESULTS: Six alleles of the CYP19 gene tetranucleotide repeat polymorphism were found in subjects: from 7 repeats to 13 repeats except 9 repeats. There was no statistically significant difference in the allele distribution of tetranucleotide repeat polymorphism in intron 4 of the CYP19 gene between patients with endometriosis and controls. Also there was no statistically significant difference in the 3 bp insertion (I)/deletion (D) polymorphism in intron 4 of the CYP19 gene between patients with endometriosis and controls. CONCLUSION: These results suggest that tetranucleotide repeat polymorphism and a 3 bp insertion (I)/deletion (D) polymorphism of the CYP19 gene are not associated with the risk endometriosis in the Korean population.
Alleles ; Aromatase* ; Endometriosis* ; Female ; Humans ; Introns ; Laparoscopy ; Laparotomy ; Microsatellite Repeats

The major issue in the development of nucleic acid based therapeutics is the inefficient delivery of these agents into cells. We prepared cholesterol conjugated spermine and evaluated its usefulness as a delivery modality for antisense oligonucleotides in HeLa-Luc cells. A 2'-O-methyl antisense oligonucleotide sequence, designed to correct splicing at an aberrant intron inserted into a normal luciferase reporter gene, was used for complex formation with cholesterol conjugated spermine. Effective delivery of this antisense agent into nucleus would results in the expression of a luciferasereporter gene product. The cholesterol-spermine formed stable complexes with the antisense oligonucleotide and showed modest delivery activity. Furthermore, this delivery activity was maintained even in the presence of serum proteins, mimicking in vivo conditions. Cholesterol-spermine thus has potential as a delivery system for antisense oligonucleotides into cells.
Blood Proteins ; Cholesterol* ; Genes, Reporter ; Introns ; Luciferases ; Oligonucleotides, Antisense ; Spermine*

BACKGROUND AND OBJECTIVES: Congenital nystagmus (CN) is an ocular oscillation that usually manifests during early infancy. To report a novel mutation in FERM domain containing 7 (FRMD7) gene in a Korean family with CN. MATERIALS AND METHODS:Genomic DNA was prepared from peripheral blood leukocytes and direct sequencing of the entire coding and adjacent intronic regions was performed to detect sequence variation of FRMD7 gene, where mutations were found recently in patients with familial CN. The family showed an X-linked pattern of inheritance without father-to-son transmission. RESULTS: Three family members with CN exhibited two sequence variations which were a novel mutation (c. 875T>C; Leu292Pro) and a polymorphism (c. 1403G>A; Arg468His, dbSNP rs#6637934). The proband was hemizygous for both variations and his mother and maternal grandmother were heterozygous carriers. CONCLUSION: This study provides an additional evidence for mutations in FRMD7 as a common cause of X-linked CN and expands its mutation spectrum.
Clinical Coding ; DNA ; Humans ; Introns ; Leukocytes ; Mothers ; Nystagmus, Congenital* ; Wills

BACKGROUND: There were few data on the gene mutations involved in the development of basal cell carcinoma(BCC) in Korean. OBJECTIVE: To gain insight into the role of p53 gene mutations of BCC in Koreans. METHODS: Fifteen BCCs were screened for mutation of the p53 gene. Immunohistochemical staining was done on the paraffin sections using a labelled streptavidin-biotin-peroxidase complex method with the primary antibody against p53 protein. Analysis of p53 mutation was done by non-isotopic RNase cleavage assay and direct sequencing. RESULTS: Mutation of p53 gene was found in 40%(6/15) of the cases. One case showed mutations in exon 6, one in exon 6 and intron 8, two in exon 8, one in exon 9, and one in intron 5. But ultraviolet specific C->T change was detected in only one case. Immunohistochemical expression of p53 was seen in 40%(6/15), but its expression did not coincide with p53 gene mutation. CONCLUSION: Ultraviolet specific mutations of p53 were much less frequent in Korean than in Caucasian, suggesting other etiologies than ultraviolet radiation.
Carcinoma, Basal Cell* ; Exons ; Genes, p53* ; Humans ; Introns ; Paraffin ; Ribonucleases

OBJECTIVE: To establish PCR (polymerase chain reaction) method for detecting factor VIII gene inversion (intron 22) causing hemophilia A, and to apply it to carrier detection of hemophilia A. DESIGN: A laboratory analysis MATERIALS AND METHODS: An inversion pattern of the factor VIII gene was analyzed in 130 unrelated Korean patients with hemophilia A and 26 female subjects using PCR. RESULTS: PCR analysis of the factor VIII gene for intron 22 inversion revealed that 91 patients (70%) were negative for the inversion, yielding 12 kb band by PQ primer. And all the other 39 (30%) patients who showed no amplification by PQ primer were positive for the inversion, yielding 11kb band by AQ primer. Among 113 patients with severe hemophilia A, 39 (35%) patients were positive for the inversion. Carrier detection for intron 22 inversion in 26 female subjects was performed, and revealed that 22 cases were carriers and 4 cases were normal female. CONCLUSION: This result suggests that PCR analysis of the inversion within the factor VIII gene is useful in the carrier detection of hemophilia A as well as in identifying hemophilia A patients with intron 22 inversion, in the Korean population.
Diagnosis* ; Factor VIII* ; Female ; Hemophilia A* ; Humans ; Introns ; Polymerase Chain Reaction*

Intron prediction is an important problem of the constantly updated genome annotation. Using two model plant (rice and Arabidopsis) genomes, we compared two well-known intron prediction tools: the Blast-Like Alignment Tool (BLAT) and Sim4cc. The results showed that each of the tools had its own advantages and disadvantages. BLAT predicted more than 99% introns of whole genomic introns with a small number of false-positive introns. Sim4cc was successful at finding the correct introns with a false-negative rate of 1.02% to 4.85%, and it needed a longer run time than BLAT. Further, we evaluated the intron information of 10 complete plant genomes. As non-coding sequences, intron lengths are not limited by a triplet codon frame; so, intron lengths have three phases: a multiple of three bases (3n), a multiple of three bases plus one (3n + 1), and a multiple of three bases plus two (3n + 2). It was widely accepted that the percentages of the 3n, 3n + 1, and 3n + 2 introns were quite similar in genomes. Our studies showed that 80% (8/10) of species were similar in terms of the number of three phases. The percentages of 3n introns in Ostreococcus lucimarinus was excessive (47.7%), while in Ostreococcus tauri, it was deficient (29.1%). This discrepancy could have been the result of errors in intron prediction. It is suggested that a three-phase evaluation is a fast and effective method of detecting intron annotation problems.
Codon ; Genome ; Genome, Plant ; Humans ; Introns ; Plants ; Triplets