• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6403-6409
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• 2013

Purpose: Biallelic germline variants of the 8-hydroxyguanine (8-OG) repair gene MYH have been associated with colorectal neoplasms that display somatic $G:C{\rightarrow}T:A$ transversions. However, the effect of single germline variants has not been widely studied, prompting the present investigation of monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC) in a Chinese population. Patients and Methods: Between January 2006 and December 2012, 400 cases of sporadic CRC and 600 age- and sex-matched normal blood donors were screened randomly for 7 potentially pathogenic germline MYH exons using genetic testing technology. Variants of heterozygosity at the MYH locus were assessed in both sporadic cancer patients and healthy controls. Univariate and multivariate analyses were performed to determine risk factors for cancer onset. Results: Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls. The region of exon 1 proved to be a linked polymorphic region for the first time, a triple linked variant including exon 1-316 $G{\rightarrow}A$, exon 1-292 $G{\rightarrow}A$ and intron 1+11 $C{\rightarrow}T$, being identified in 13 CRC patients and 2 normal blood donors. A variant of base replacement, intron 10-2 $A{\rightarrow}G$, was identified in the exon 10 region in 21 cases and 7 controls, while a similar type of variant in the exon 13 region, intron 13+12 $C{\rightarrow}T$, was identified in 8 cases and 6 controls. Not the only but a newly missense variant in the present study, p. V463E (Exon 14+74 $T{\rightarrow}A$), was identified in exon 14 in 6 patients and 1 normal control. In exon 16, nt. 1678-80 del GTT with loss of heterozygosity (LOH) was identified in 27 CRC cases and 26 controls. There was no Y165C in exon 7 or G382D in exon 14, the hot-spot variants which have been reported most frequently in Caucasian studies. After univariate analysis and multivariate analysis, the linked variant in exon 1 region (p=0.002), intron 10-2 $A{\rightarrow}G$ (p=0.004) and p. V463E (p=0.036) in the MYH gene were selected as 3 independent risk factors for CRC. Conclusions: According to these results, the linked variant in Exon 1 region, Intron 10-2 $A{\rightarrow}G$ of base replacement and p. V463E of missense variant, the 3 heterozygosity variants of MYH gene in a Chinese population, may relate to the susceptibility to sporadic CRC. Lack of the hot-spot variants of Caucasians in the present study may due to the ethnic difference in MYH gene.

• Journal of Plant Biology
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• v.38 no.2
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• pp.137-141
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• 1995

We isolated a cDNA clone, BLSC1, encoding 5' exon of ATP synthase CF0 subunit I from broccoli. BLSC1 is 285 nucleotides long which consists of a 5' noncoding region of 34 nucleotides, a 5' exon of 145 nucleotides and an intron of 106 nucleotides. The 5' exon codes for 48 amino acids which reveals mostly hydrophobic. The amino acid sequence deduced from BLSC1 shares 83%, 83% and 91% identities with the genes coding for atpF from wheat, rice and spinach, respectively. Genomic Southern blot analysis for BLSC1 showed a typically strong signal for a gene located in the chloroplast genome. Northern blot analysis identified three major classes of transcripts showing strong positive signals in the leaves, but only trace amounts of the transcripts were identified in the other organs like stems, flowr buds and roots.

• Genomics & Informatics
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• v.7 no.2
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• pp.131-135
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• 2009

Domains are the building blocks of proteins. Exon shuffling is an important mechanism accounting for combination of a limited repertoire of protein domains in the evolution of multicellular species. A relative excess of domains encoded by symmetric exons in metazoan phyla has been presented as evidence of exon shuffling, and symmetric domains can be divided into old and new domains by determining the ages of the domains. In this report, we compare the spread, versatility, and subcellular localization of old and new domains by analyzing eight metazoan genomes and their respective annotated proteomes. We found that new domains have been expanding as multicellular organisms evolved, and this expansion was principally because of increases in class 1-1 domains amongst several classes of domain families. We also found that younger domains have been expanding in membranes and secreted proteins along with multi-cellular organism evolution. In contrast, old domains are located mainly in nuclear and cytoplasmic proteins. We conclude that the increasing mobility and versatility of new domains, in contrast to old domains, plays a significant role in metazoan evolution, facilitating the creation of secreted and transmembrane multidomain proteins unique to metazoa.

• Annals of Clinical Neurophysiology
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• v.14 no.2
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• pp.53-58
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• 2012

For the last decades, molecular genetics has achieved great advances that the genes on the list of inherited muscle diseases are piling up. Those diseases of overlapping clinico-pathologic findings are now understood with discrete molecular pathogeneses. We are facing an exciting era that the long-waited gene therapy may eventually come true. Skipping of dystrophin exon 51 is on successful clinical trials, which will benefit about 13% of the children suffering from Duchenne muscular dystrophy. Exon skipping is under active investigation to expand the candidates. Hopefully it may cover majority of Duchenne muscular dystrophy mutations and some of other diseases. Adeno-associated virus is one of the most versatile tools for gene transfer. It may overcome the limitation of exon skipping. Here we review exon skipping technique of Duchenne muscular dystrophy and briefly discuss the other strategies being studied to cure inherited muscle diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5659-5663
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• 2012

To investigate the expression of hPOT1 in the HeLa cell line and screen point mutations of hpot1 in different tumor tissues a two step osmotic method was used to extract nuclear proteins. EMSA was performed to determine the expression of hPOT1 in the HeLa cell line. PCR was also employed to amplify the exon14 sequence of the hpot1 gene in various of cancer tissues. A SV gel and PCR clean-up system was performed to enrich PCR products. DNAStar was used to analyse the exon14 sequence of the hpot1 gene. hPOT1 was expressed in the HeLa cell line and the signal was gradually enhanced as the amount of extracted nuclear proteins increased. The DNA fragment of exon14 of hpot1 was successfully amplified in the HeLa cell line and all cancer tissues, point mutations being observed in 2 out of 3 cases of endometrial cancer (66.7%) despite the hpot1 sequence being highly conserved. However, the sequence of hpot1 exon14 do not demonstrate point mutations in most cancer tissues. Since hPOT1 was expressed in HeLa cell and the probability of gene point variants was obviously higher in endometrial cancer than other cancers, it may be involved in the pathogenesis of gynecological cancers, especially in cervix and endometrium.

• BMB Reports
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• v.50 no.8
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• pp.423-428
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• 2017

SRSF2, a Serine-Arginine rich (SR) protein, is a splicing activator that mediates exon inclusion and exclusion events equally well. Here we show SRSF2 directly suppresses intron splicing to suppress cassette exon inclusion in SMN pre-mRNA. Through a serial mutagenesis, we demonstrate that a 10 nt RNA sequence surrounding the branch-point (BP), is important for SRSF2-mediated inhibition of cassette exon inclusion through directly interacting with SRSF2. We conclude that SRSF2 inhibits intron splicing to promote exon exclusion.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4521-4524
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• 2015

Background: Endometrial carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in Iranian women after breast, colorectal and lung cancers. Various genetic alterations appear to be early events in the pathogenesis of endometrial carcinoma and it seems that PTEN is the most commonly mutated gene in the endometrioid subtype. The aim of the present study was to investigate the correlation between mutations in exon 7 of PTEN gene and endometrial carcinoma. Materials and Methods: Seventy-five patients with endometrial carcinoma and 75 females whose underwent hysterectomy for non tumoral indication were selected for evaluation of PTEN mutations in exon 7 by PCR-SSCP and sequencing. Correlations between the frequency and type of mutation and the pathologic findings of the cancer (tumor subtype, stage and grade) were assessed. Results: All of the samples were obtained from Iranian patients. 60 % (45 cases) of the tumors were endometriod and 40% (30 cases) were of serous type. The grade distributions of the 75 cases according to the FIGO staging system were as follows: low grade, 20 cases; high grade 55 cases, low stage, 41 cases; high stage 34 cases. For exon 7 of the PTEN gene, the analysis showed that there were no mutations in our cases. Conclusions: Our findings in the present study suggest that exon 7 of PTEN does not play any significant role in the development of endometrial carcinoma in Iranian cases.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.18 no.2
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• pp.154-161
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• 2007

Objectives: The aim of the current study is to test for the association of DRD4 exon III VNTR polymorphism with attention-deficit hyperactivity disorder(ADHD) in Korean children population. Methods: 113 Korean children with ADHD, 102 parents, and 133 control subjects participated with the current study. The distribution of genotypes and alleles of DRD4 exon III VNTR in children with ADHD was compared with that in control subjects. In addition, 69 children with ADHD and their parents were analyzed using the transmission disequilibrium test(TDT). Results: We could not find any significant differences in the distribution of genotypes and alleles at DRD4 exon III VNTR polymorphism between children with ADHD and control subjects. In addition, there was no preferential transmission of long allele of DRD4 exon III VNTR polymorphism. Conclusion: These results suggest that DRD4 is not associated with ADHD in Korean children population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1321-1324
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• 2012

Background: DNA polymerase beta ($pol{\beta}$) is a key enzyme in the base excision repair pathway. It is 39kDa protein, with two subunits, one large subunit of 31 kDa having catalytic activity between exon V to exon XIV, and an 8 kDa smaller subunit having single strand DNA binding activity. Exons V to VII have double strand DNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XII to XIV the dNTP selection activity. Aim: To examine the association between $pol{\beta}$ polymorphisms and the risk of ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastatic normal samples from the same patients. In this study, mutational analysis of $pol{\beta}$ genomic DNA was undertaken using primers from exons IX to XIV - the portion having catalytic activity. Results: We detected alteration in DNA polymerase beta by SSCP. Two specific heterozygous point mutations of $pol{\beta}$ were identified in Exon 9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlation study involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous type with a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type and stage IV together have shown Pearson ${\chi}^2$ value of 3.28 with likelihood ratio of 4.4 (p=0.07) with OR =2.08 (0.3-14.55). This indicates that there is a tendency of correlation among polymorphism 2, serous type and stage IV, indicating a risk factor for ovarian cancer. Conclusion: Hence, the results indicate that there is a tendency for $pol{\beta}$ polymorphisms being a risk factor for ovarian carcinogenesis in India.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2879-2883
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• 2013

Objective: To investigate differences in mutations of epidermal growth factor receptor (EGFR) gene and relationships with clinicopathological features in patients with non-small cell lung cancer (NSCLC) between Uygur and Han ethnic groups. Methods: The Scorpions amplification refractory mutation system (Scorpions ARMS) was used to measure mutations in exons 18, 19, 20 and 21 of the EGFR gene in paraffin-embedded tumor tissue from NSCLC cases, and statistical analysis was performed to investigate links with clinicopathological features in different histological types of NSCLC. Results: Results from ARMS testing showed EGFR mutations in tumor tissues from six (6) of 50 NSCLC patients of Uygur ethnic group, with a positive rate of 12.0%; four of them (4) had exon 19 deletion in EGFR, and two (2) had L858R point mutation in exon 21 of EGFR. Statistically significant difference was noted in EGFR genetic mutation between adenocarcinoma and non-adenocarcinoma (P < 0.05), but no differences with gender, age group, smoking status, or stage (P > 0.05). EGFR mutations were detected in tumor tissues from 27 of 49 NSCLC patients of Han ethnic group, with a positive rate of 55.1%; 19 of them had exon 19 deletions, seven (7) had L858R point mutations in exon 21 of EGFR and one (1) had mutations in both exon 18 G719X and exon 20 T790M of EGFR. Statistically significant differences were noted in EGFR genetic mutations between genders and between adenocarcinoma and non-adenocarcinoma (P<0.05), but not with age group, smoking status, or stage (P > 0.05). Conclusion: Statistically significant differences were noted in the positive rates of EGFR genetic mutations in NSCLC patients between Uygur and Han ethnic groups, with lower positive rates for the Uygur cases.