PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “intronic polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1999

[Presinilin 1 gene polymorphism and Alzheimer's disease in Chinese].

OBJECTIVE: To detect the relationship between Presinilin 1(PS1) intronic polymorphism and Alzheimer's disease(AD) in Chinese. METHODS: PS1 intronic polymorphism was genotyped in 58 early-onset AD cases(EOAD), 65 late-onset AD cases (LOAD) and 157 age-matched controls by using PCR methods and RFLP typing. Then the association between PS1 polymorphism and AD was analyzed. RESULTS: (1) In EOAD cases, the frequency of allele 1 increased and the frequencies of allele 2 and genotype 2/2 decreased markedly, but in LOAD cases, no differences were observed. (2) EOAD was significantly associated with allele 1 (RR=2.29), P< 0.05), allele 2 (RR=0.44) and genotype 2/2(RR=0.23, P<0.05) of PS1 polymorphism, while LOAD showed no association with PS1 polymorphism. (3)PS1 polymorphism was associated with AD predominantly in non-ApoE epsilon4, female, early-onset cases. CONCLUSION: PS1 polymorphism was only associated with EOAD in Chinese, and this may be influenced by age of onset and sex.

Aged↗
PubMed1998

Analysis of Four Common Salt-Wasting Mutations in CYP21 (Steroid 21-Hydroxylase) by Cleavase Fragment Length Polymorphism Analysis and Characterization of a Frequent Polymorphism in Intron 6.

Background: Congenital adrenal hyperplasia (CAH) owing to steroid 21-hydroxylase deficiency results from mutations in CYP21. The majority of patients with this disorder have salt-wasting because of mineralocorticoid deficiency, and most patients with salt-wasting have one of four common mutations: deletions of CYP21, or nondeletion mutations including a 3 < 9 premature splice mutation in intron 2; an 8-bp deletion in exon III; a cluster of mutations in exon VI; and R356W. Methods and Results: The authors analyzed these mutations using a new mutation-detection methodology, cleavase fragment length polymorphism (CFLP) analysis. All of these mutations were detectable using CFLP. The intron 2 splice mutation, exon III 8-bp deletion, and R356W mutation all resulted in novel CFLP bands not seen in subjects without those mutations. The exon VI cluster of mutations resulted in elimination of a CFLP band, which was easily detected in a patient with that mutation and a gene deletion on the homologous chromosome. The authors also report the characterization of a restriction fragment length polymorphism in intron 6 involving the RsaI site around nucleotide 1419. In 48 chromosomes from the parental generation of the Centre d'Étude du Polymorphisme Humain families, the frequency of the polymorphism that destroys the RsaI site was found to be 12.5%. Conclusions: CFLP is a potentially useful analytic method for analyzing frequent CYP21 mutations that cause salt-wasting CAH, although further development of the technique is required to clearly distinguish heterozygotes from homozygotes for mutations that generate novel CFLP bands and to identify heterozygotes for mutations that eliminate a CFLP band. The Rsa I polymorphism may be a useful marker for following the segregation of CYP21 alleles in genetic studies and is of use in showing gene deletions of CYP21 in informative families. The polymorphism may also be of use in genetic studies of the human major histocompatibility complex.

Journal Article↗
PubMed2007

Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians.

Intron 1 of the interferon-gamma (IFNG) gene contains two polymorphisms. The 12 CA-repeat allele of the +875 IFNGCA microsatellite and the T allele of the +A874T single nucleotide polymorphism (SNP) have been associated with increased in vitro IFNG production and a variety of clinical phenotypes. The purpose of this study was to determine whether these polymorphisms influence total serum IgE levels [tsIgE] and the outcome of a hepatitis B virus (HBV) infection. IFNGCA and +A874T were typed in 186 asthmatics of Niuean ancestry and in Polynesian women with a chronic HBV infection (n = 60) and with natural immunity to the HBV (n = 66). The IFNGCA genotype was associated with [tsIgE] in asthmatic children (n = 51, p = 0.004) but not adults (n = 135, p = 0.87). The data were consistent with a co-dominant influence of the 12 CA-repeat allele on high [tsIgE]. The IFNGCA genotype was also associated with the risk for chronic HBV infection (chi (2) = 11.6, p = 0.003) because of a dominant effect of the 12 CA-repeat allele on developing natural immunity in homozygotes (OR = 5.8, p = 0.003) and heterozygotes (OR = 2.7, p = 0.01). Similar associations were found for the T allele of the +A874T SNP. The possibility that these associations were due to linked alleles in the adjacent 783 bp of the promoter and 3'-untranslated region of the IFNG gene was excluded by direct sequencing. In summary, high-IFNG-producing alleles in intron 1 of the IFNG locus are associated with high [tsIgE] in asthmatic children from Niue and with natural immunity to the HBV in Polynesian women. These findings are consistent with a previous report of an association between +875 IFNGCA and [tsIgE] and provide preliminary evidence of a new association with the outcome of an HBV infection.

Adolescent↗
PubMedDate not supplied

Evaluation of a polymorphism in intron 2 of the p53 gene in ovarian cancer patients. From the Danish "Malova" Ovarian Cancer Study.

BACKGROUND: The p53 gene is frequently mutated in various human tumours. In addition, single nucleotide polymorphisms are often observed in exons and introns of the p53 gene in normal tissues and tumours. MATERIALS AND METHODS: A total of 210 blood and tissue samples from 182 ovarian cancers (OC) and 28 ovarian borderline tumours, in addition to blood samples from 72 healthy women, were analysed. The used analyses were PCR and SSCP. The distinguishable SSCP patterns were confirmed by DNA sequencing. RESULTS: A polymorphism located at position 38 in intron 2 of the p53 gene was studied in blood and tumour tissues from Danish ovarian tumour patients and in blood from controls. Significant differences were found between the distributions of the genotypes in blood samples compared to the corresponding tissue samples (p = 0.0002). A tendency towards a significant difference in survival was observed between OC stage II patients with a shift from one genotype in the blood to another genotype in the tissue and patients with no shift (p = 0.05). In multivariate COX regression analysis restricted to stage III OC patients, the only independent factors found were shift, serum-tetranectin and age. CONCLUSION: A shift from one p53 intron 2 genotype in the blood to another genotype in the tissue may be a prognostic factor in ovarian cancer patients.

Adult↗
PubMed2001

Identification of novel polymorphisms in intron 7 of the human p53 gene in acute myeloid leukemia and healthy donors.

Screening for mutations by PCR-SSCP in exons 5 to 9 of the p53 gene in 38 bone marrow or peripheral blood specimens of patients with acute myeloid leukemia (AML) showed abnormal shifts in 9 cases. One reflected a mutation in exon 8, whereas in the other cases there were no exonic mutations identified by sequencing. As PCR primers were chosen annealing in the introns flanking the exon region, following sequencing of the encompassing introns identified 5 base substitutions at various sites in intron 7. Two of them have been described previously [1] and 3 novel polymorphisms could be identified. To determine whether these polymorphisms are linked to the pathogenesis of AML, we screened peripheral blood specimens of 26 healthy controls. We found identical base substitutions in 6 out of 26 controls. Our data suggest that these polymorphisms are not related to the pathogenesis of AML.

Acute Disease↗
PubMed2006

Association between obsessive-compulsive disorder and a variable number of tandem repeats polymorphism in intron 2 of the serotonin transporter gene.

BACKGROUND: Pharmacological studies indicate a dysregulation of the serotonergic system in obsessive-compulsive disorder (OCD). A variable number tandem repeats (VNTR) polymorphism with three alleles (Stin2.9, Stin2.10, Stin2.12) has been described in intron 2 of the serotonin transporter (5-HTT) gene. This polymorphism has been associated with unipolar depression, bipolar disorder, schizophrenia, and anxiety disorders including OCD. METHODS: The association between OCD and the polymorphism is examined in 97 OCD patients, 578 psychiatric controls and 406 healthy controls, all Spanish Caucasians. RESULTS: Genotype frequencies for the polymorphism were significantly different in OCD patients, psychiatric patients and controls. There was a significant excess of 12/12 and 12/10 genotypes in OCD patients compared to psychiatric patients and controls. CONCLUSIONS: Our results indicate a possible association between the Stin2.12 allele of the VNTR polymorphism and OCD.

Alleles↗
PubMed1997

[Molecular genetic analysis of TUB18 and TUB20 intragenic polymorphism and various mutations of the CFTR gene in the Moscow region].

Allelic frequencies of two intron polymorphisms in the cystic fibrosis transmembrane regulator (CFTR) gene, TUB18 and TUB20, were estimated on chromosomes of 67 cystic fibrosis patients and on that of 37 healthy donors from Moscow and the Moscow oblast. Allele 2 of the TUB 18, and allele 1 of the TUB20 were 2.1 and 1.5 times more frequent on the non-delta F508 chromosomes of the cystic fibrosis patients than on chromosomes of healthy donors, i.e. these alleles were in linkage disequilibrium with the CFTR gene. Allele 1 of the TUB18 marker and allele 2 of the TUB20 marker demonstrated absolute linkage disequilibrium with the delta F508 mutation of the CFTR gene. The degree of association between the TUB18 and TUB20 intron polymorphisms and the GATT and T854T intragenic polymorphisms was analyzed. Of all 62 delta F508 chromosomes tested, 98.3% shared the 2-1-1-2 GATT- T854T-TUB18-TUB20 haplotype. Eight major (more frequent) GATT-T854T-TUB18-TUB20 haplotypes were found in 89.5% of normal, and in 97.9% of non-delta F508 chromosomes of cystic fibrosis patients from the Moscow region. Three of these major haplotypes, 2-1-1-2, 1-2-2-1, and 2-2-1-2, were respectively 2.5, 2, and 1.5 times more frequent on non-delta F508 cystic fibrosis chromosomes than on normal chromosomes. Data on screening for the G542X, N1303K, and 394delTT mutations of the CFTR gene, carried out on 134 chromosomes of cystic fibrosis patients from the Moscow region are presented. The frequencies of the G542X and 394delTT mutations were estimated as 1.5%, while the frequency of the N1303K mutation was 2.2%.

Alleles↗
PubMed2005

Assignment of the gene for porcine insulin-like growth factor binding protein 1 to chromosome 18 and detection of polymorphisms in intron 2 by PCR-RFLP.

We have obtained a partial cDNA and three BAC clones for the porcine insulin-like growth factor binding protein 1 gene (IGFBP-1). Results of fluorescence in situ and radiation hybrid (RH) mapping assigned this gene to porcine chromosome (SSC) 18q24-qter. We found two types of polymerase chain reaction-restriction-fragment-length polymorphisms (PCR-RFLP) in intron 2 by using FokI and AluI.

Animals↗
PubMed1992

Exonic polymorphism vs intronic simple repeat hypervariability in MHC-DRB genes.

Gene products encoded by the major histocompatibility complex often exhibit a high degree of polymorphism. In humans the HLA-DR polymorphism is due to more than 50 alleles with varying exon 2 sequences. Each group of DRB alleles contains a certain form of the basic simple repeat motif (gt)n(ga)m in intron 2. Identical alleles can be differentiated on the basis of the hypervariable repeat. In this study focused on cattle (Bos taurus) we identified different Bota-DRB alleles in a limited survey by amplification via polymerase chain reaction and sequencing. In addition DRB exon 2 sequences were also obtained from eight additional hoofed animal species (seven horned artiodactyls and one pig) revealing artiodactyl-specific polymorphic and nonpolymorphic substitutions. In the genus Bos the intronic simple repeat variability was compared with exonic DRB polymorphism. As in humans all Bota-DRB exons were always associated with specifically organized basic simple repeat structures. Yet the extent of simple repeat variability was lower in cattle compared to humans. Selective breeding in the process of domestication might be responsible for the diminished intronic hypervariability. Nevertheless, the hypermutable simple repeat sequences have been preserved in the same position and with the same principal structure for at least 70 x 10(6) years of evolution. Unexpectedly, the rate of intronic simple repeat and exonic changes appear quite similar.

Alleles↗
PubMed2007

A novel polymorphisms in intron 12 of the bovine calpastatin gene.

Calpastatin (CAST) is a specific inhibitor of the ubiquitous calcium-dependent proteases-mu-calpain and m-calpain, found in mammalian tissues. This proteolytic system plays a key role in the tenderization process that occurs during post-mortem storage of meat under refrigerated conditioning. Fragments of the bovine CAST gene including intron 12 were amplified and subjected to SSCP analysis. Four new SNPs were found within intron 12 of the CAST gene: a transition T/C at position 3893+155* A/G at position 3893+163, a transversion T/A at position 3893+223 and a substitution A/G at position 3893+428 (consensus sequence--GenBank AY834771). The genetic variants in the bovine CAST gene can be analyzed with RFLP method and was studied in 375 bulls of six breeds, including Hereford, Aberdeen-angus, Simmental, Charolaise, Limousine and Polish Black-and-White (BW; Fresian) breeds.

Animals↗
PubMed1999

Identification of novel single nucleotide polymorphisms in intron 1B and exon 1C of the human interleukin-1 receptor type I (IL-1RI) gene.

We have identified two novel single nucleotide polymorphisms in the 5' region of the human IL-1RI gene: (1) A-->G at position 52 in intron 1B (GenBank accession number AF146426), which creates an Mspl restriction endonuclease site. Allele frequencies in a Caucasian population were 0.1 (A allele) and 0.9 (G allele). (2) A-->T at position 140 in exon 1C (GenBank accession number AF146427). Allele frequencies in a Caucasian population were 0.27 (A allele) and 0.73 (T allele).

Base Sequence↗
PubMed1997

An unusual combined insertion/deletion polymorphism in intron 10 of the human complement C6 gene.

Investigation of intron 10 of the human complement C6 gene revealed an unusual combined insertion/deletion polymorphism at position 493: the subsequent 6 bp is deleted and is substituted by a different 26 bp, giving a net gain of 20 bp. The variant shows autosomal co-dominant inheritance. The 26 bp insertion is homologous to a human endogenous retrovirus-type sequence and could tentatively be ascribed to a retroposon. Alternatively, the presence of three copies of a 5 bp direct repeat, an 8 bp palindrome and a 12 bp split symmetrical element could suggest an endogenous, sequence-mediated mutational process. Polymorphisms of this type are extremely rare, although there are several examples of such mutations causing disease.

Base Sequence↗
PubMed2001

Genomic structure and loss of heterozygosity of EPHB2 in colorectal cancer.

EphB2, a member of the Eph receptor protein-tyrosine kinase family, is overexpressed in several human gastrointestinal tumors. Furthermore, the EphB2 gene is localized at 1p35-p36.1, a frequently deleted region in colon and other cancers. So, despite its overexpression in some kind of tumors, we decided to study the possibility of involvement in the EphB2 gene (EPHB2) mutation in colon cancers, because some of the well known tumor suppressor genes (e.g. p53) is overexpressed (really accumulated) in tumors. Fifty colon tumor samples of matched with their respective normal tissues, were studied for mutation of the EPHB2. Analysis of the genomic structure of EphB2 and survey of all 16 exons revealed an infrequent polymorphism (intron 2) and mutation (intron 8). Another polymorphism in exon 6, localized at nucleotide 1359 (A-->G) was found to be rather frequent in Japanese and Chinese subjects, but very rare in Caucasians. Taking advantage of this polymorphism within EPHB2, we surveyed the loss of heterozygosity (LOH) status of this gene in Japanese colorectal tumors. Among the 50 samples analyzed, 24 were informative, and LOH was found in five of the15 (33.3%) informative rectal cancer cases. Mutation analysis covering all 16 exons in the remaining allele did not reveal any mutations. Thus, EPHB2 is not a classical tumor suppressor gene.

Aged↗
PubMed1996

A minisatellite polymorphism in intron III of the barramundi (Lates calcarifer) growth hormone gene.

This paper describes the detection of a polymorphism within the growth hormone (GH) gene of the fish barramundi (Lates calcarifer). PCR amplification of barramundi genomic DNA generated three different sized products: A, 409 bp; B, 478 bp; and H, 520 bp. Each barramundi isolate displayed one of four different types of profiles, which contained specific combinations of these PCR products. Sequence analysis confirmed that products A and B are different forms of the barramundi GH gene, and studies showed that product H was an artifact due to heteroduplex formation between the two smaller-sized molecules. The polymorphic nature of these PCR products was due to differences in the number of repeat monomers within the 5' end of the barramundi decaminisatellite, an AT-rich repetitive sequence that was identified within intron III of this gene. The barramundi decaminisatellite consisted of 24 or 28 10-nucleotide imperfect direct repeat monomers in a tandem array. The monomers were grouped into one of three different families and evidence for monomer homogenization by crossover fixation was presented. The barramundi decaminisatellite differed from previously reported AT- or GC-rich minisatellites, although a similar decaminisatellite has been identified in intron III of the tilapia GH gene.

Animals↗
PubMed2005

Functional IFNG polymorphism in intron 1 in association with an increased risk to promote sporadic breast cancer.

Interferon (IFN)-gamma is an important Th1 cytokine, which plays a role in immune surveillance and anti-tumor activity. A case-control study involving 54 sporadic breast cancer patients and 144 healthy controls was carried out to explore if the genotype variation of a proposed non-specific enhancer element with a dinucleotide (CA)n repeat in intron 1 has a role in the susceptibility to promote sporadic breast cancer. Genotype analysis carried out by single-strand length polymorphism and confirmed by sequencing showed an increased frequency of (CA)12 allele (P<0.001) and decreased frequencies of (CA)15 (P<0.01) and (CA)>15 (p<0.001) alleles in sporadic breast cancer patients as compared to controls. Further, in vitro reporter assays for (CA)12 and (CA)15 alleles suggested these to be associated with decreased and increased expressions, respectively, suggesting the (CA)12/(CA)12 background to act as one of the factors that could lead to low production of IFN-gamma. The study concludes that such genetic background for a proposed non-specific enhancer element with (CA)n repeat within intron 1 of the IFNG gene might put the individuals with this genotype at higher risk to promote the development of sporadic breast cancer due to a resultant compromised immune surveillance.

Alleles↗
PubMed2004

Polymorphisms and intronic structures in the 18S subunit ribosomal RNA gene of the fungi Scytalidium dimidiatum and Scytalidium hyalinum. Evidence of an IC1 intron with an His-Cys endonuclease gene.

The fungi Scytalidium dimidiatum (Nattrassia mangiferae synanamorph) and Scytalidium hyalinum are mainly encountered in (sub)tropical areas as plant pathogens and agents of human dermatomycosis. Because the classification and differentiation of these two species is unclear, we studied 22 S. dimidiatum and 15 S. hyalinum isolates in order to identify potential species-specific insertions and polymorphisms in the 18S subunit ribosomal gene. The presence of an IE intron in S. dimidiatum, together with a single polymorphism (A in S. dimidiatum, G in S. hyalinum) in the coding region, allowed us to differentiate these two species in most cases. Moreover, in one S. dimidiatum isolate we found a group IC1 intron containing a putative truncated His-Cys endonuclease gene. This enzyme shows strong similarity to the intronic homing endonuclease of Physarum polycephalum. Based on these results and our previous findings, we propose an evolutionary pathway for 18S rDNA S. dimidiatum insertions, implying independent events.

Ascomycota↗