Displaying publications 1 - 20 of 59 in total

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  1. Low level of TERC gene amplification between chronic myeloid leukaemia patients resistant and respond to imatinib mesylate treatment
    Mohamad Ashari ZS, Sulong S, Hassan R, Husin A, Sim GA, Abdul Wahid SF
    Asian Pac J Cancer Prev, 2014;15(4):1863-9.
    PMID: 24641422
    The amplification of telomerase component (TERC) gene could play an important role in generation and treatment of haematological malignancies. This present study was aimed to investigate copy number amplification status of TERC gene in chronic myeloid leukaemia (CML) patients who were being treated with imatinib mesylate (IM). Genomic DNA was extracted from peripheral blood of CML-IM Resistant (n=63), CML-IM Respond (n=63) and healthy individuals (n=30). TERC gene copy number predicted (CNP) and copy number calculated (CNC) were determined based on Taqman® Copy Number Assay. Fluorescence in situ hybridization (FISH) analysis was performed to confirm the normal signal pattern in C4 (calibrator) for TERC gene. Nine of CML patients showed TERC gene amplification (CNP=3), others had 2 CNP. A total of 17 CML patients expressed CNC>2.31 and the rest had 2.31>CNC>1.5. TERC gene CNP value in healthy individuals was 2 and their CNC value showed in range 1.59-2.31. The average CNC TERC gene copy number was 2.07, 1.99 and 1.94 in CML- IM Resistant patients, CML-IM Respond and healthy groups, respectively. No significant difference of TERC gene amplification observed between CML-IM Resistant and CML-IM Respond patients. Low levels of TERC gene amplification might not have a huge impact in haematological disorders especially in terms of resistance towards IM treatment.
    Matched MeSH terms: DNA Copy Number Variations
  2. Fulltext The identification of copy number variation of CNV ESV27061 among young adults with hypertension: preliminary findings. [Abstract]
    Shaik Alaudeen SR, Mohd Shah AS, Abdul Talib N, Abdullah A
    International Medical Journal Malaysia, 2017;16(11):31.
    MyJurnal
    Introduction: Hypertension related morbidities and mortalities around the world show a gradual increase and early detection and prevention are advocated. The Database of Genomic Variants (DGV) has associated variation in DNA sequences called copy number variation (CNV) with susceptibility to common diseases. However, little is known about CNV role in essential hypertension. Thus, this study aimed to characterize the CNV esv27061 among prehypertensive and hypertensive young adults in Malaysia. Materials and method: In this comparative cross-sectional study, 104 subjects living in Kuantan who gave voluntary consent to participate are recruited and divided into three groups; control (43 subjects), prehypertensive (38 subjects) and mild hypertensive (23 subjects). An optimized droplet digital polymerase chain reaction (ddPCR) was used in the determination of CNV esv27061 in this study. Results: All subjects in the control (n=38; 88.4% gain), prehypertensive (n=33; 86.8% gain) and mild hypertensive (n=21; 91.3% gain) groups had CNV gain (copy number > 2) while 11.6% of control, 13.2% of prehypertensive and 8.7% of mild hypertensive subjects exhibited normal copies (copy number = 2). Conclusion: The present preliminary finding was consistent with the Database of Genomic Variants (DGV) which stated that CNV esv27061 showed more gain than loss.
    Matched MeSH terms: DNA Copy Number Variations
  3. Fulltext A novel rare copy number variant of the ABCF1 gene identified among dengue fever patients from Peninsular Malaysia
    Hoh BP, Sam SS, Umi SH, Mahiran M, Nik Khairudin NY, Rafidah Hanim S, et al.
    Genet. Mol. Res., 2014;13(1):980-5.
    PMID: 24634119 DOI: 10.4238/2014.February.19.9
    Copy number variation (CNV) is a form of genetic variation in addition to single nucleotide polymorphisms. The significance of CNV in the manifestation of a number of diseases is only recently receiving considerable attention. We genotyped 163 dengue patients from Peninsular Malaysia for genes possibly linked to dengue infection using quantitative real-time PCR. Here, we report a serendipitous discovery of a novel rare CNV of the ABCF1 gene among the dengue patients. Among these patients, two had a gain of 1 copy (CN = 3) and one had lost 1 copy (CN = 1), indicating that a rare CNV of the ABCF1 gene was detected among dengue patients from Peninsular Malaysia. Although the gene is suspected to regulate inflammatory responses and pathogen-induced cytokine storm, its relevance to dengue requires further investigation.
    Matched MeSH terms: DNA Copy Number Variations*
  4. Fulltext Copy number variation of CCL3L1 among three major ethnic groups in Malaysia
    Jamaluddin J, Mohd Khair NK, Vinodamaney SD, Othman Z, Abubakar S
    BMC Genet, 2020 01 03;21(1):1.
    PMID: 31900126 DOI: 10.1186/s12863-019-0803-3
    BACKGROUND: C-C motif Chemokine Ligand 3 Like 1 (CCL3L1) is a multiallelic copy number variable, which plays a crucial role in immunoregulatory and hosts defense through the production of macrophage inflammatory protein (MIP)-1α. Variable range of the CCL3L1 copies from 0 to 14 copies have been documented in several different populations. However, there is still lack of report on the range of CCL3L1 copy number exclusively among Malaysians who are a multi-ethnic population. Thus, this study aims to extensively examine the distribution of CCL3L1 copy number in the three major populations from Malaysia namely Malay, Chinese and Indian. A diploid copy number of CCL3L1 for 393 Malaysians (Malay = 178, Indian = 90, and Chinese = 125) was quantified using Paralogue Ratio Tests (PRTs) and then validated with microsatellites analysis.

    RESULTS: To our knowledge, this is the first report on the CCL3L1 copy number that has been attempted among Malaysians and the Chinese ethnic group exhibits a diverse pattern of CCL3L1 distribution copy number from the Malay and Indian (p number among major ethnic groups in the Malaysian population is found to be significantly varied when compared to the European population (p number.

    Matched MeSH terms: DNA Copy Number Variations*
  5. Fulltext Somatic copy-neutral loss of heterozygosity and copy number abnormalities in Malaysian sporadic colorectal carcinoma patients
    Yam YY, Hoh BP, Othman NH, Hassan S, Yahya MM, Zakaria Z, et al.
    Genet. Mol. Res., 2013;12(1):319-27.
    PMID: 23420356 DOI: 10.4238/2013.February.7.1
    Colorectal cancer is one of the most common cancers in many countries, including Malaysia. The accumulation of genomic alterations is an important feature of colorectal carcinogenesis. A better understanding of the molecular events underlying the stages of colorectal carcinogenesis might be helpful in the detection and management of the disease. We used a commercially available single-nucleotide polymorphism genotyping array to detect both copy number abnormalities (CNAs) and copy-neutral loss of heterozygosity (LOH) in sporadic colorectal carcinomas. Matched tumor and normal tissues of 13 colorectal carcinomas (Dukes' stages A-D) were analyzed using a 250K single nucleotide polymorphism array. An additional assay was performed to determine the microsatellite instability status by using the National Cancer Institute-recommended BAT-26 panel. In general, copy number gain (92.3%) was most common, followed by copy number loss (53.8%) and copy-neutral LOH (46.2%). Frequent CNAs of gains and losses were observed on chromosomes 7p, 8, 13q, 17p, 18q, and 20q, and copy-neutral LOH was observed on chromosomes 2, 6, 12, 13q, 14q, 17, 20p, 19q, and 22q. Even though genomic alterations are associated with colorectal cancer progression, our results showed that DNA CNAs and copy-neutral LOH do not reflect disease progression in at least 50% tumors. Copy-neutral LOH was observed in both early and advanced tumors, which favors the involvement of these genomic alterations in the early stages of tumor development.
    Matched MeSH terms: DNA Copy Number Variations*
  6. Fulltext A comparison of assays for accurate copy number measurement of the low-affinity Fc gamma receptor genes FCGR3A and FCGR3B
    Haridan US, Mokhtar U, Machado LR, Abdul Aziz AT, Shueb RH, Zaid M, et al.
    PLoS One, 2015;10(1):e0116791.
    PMID: 25594501 DOI: 10.1371/journal.pone.0116791
    The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method's performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs.
    Matched MeSH terms: DNA Copy Number Variations/genetics
  7. Fulltext Development of High Resolution Melting Analysis for the Diagnosis of Human Malaria
    Chua KH, Lim SC, Ng CC, Lee PC, Lim YA, Lau TP, et al.
    Sci Rep, 2015;5:15671.
    PMID: 26507008 DOI: 10.1038/srep15671
    Molecular detection has overcome limitations of microscopic examination by providing greater sensitivity and specificity in Plasmodium species detection. The objective of the present study was to develop a quantitative real-time polymerase chain reaction coupled with high-resolution melting (qRT-PCR-HRM) assay for rapid, accurate and simultaneous detection of all five human Plasmodium spp. A pair of primers targeted the 18S SSU rRNA gene of the Plasmodium spp. was designed for qRT-PCR-HRM assay development. Analytical sensitivity and specificity of the assay were evaluated. Samples collected from 229 malaria suspected patients recruited from Sabah, Malaysia were screened using the assay and results were compared with data obtained using PlasmoNex(TM), a hexaplex PCR system. The qRT-PCR-HRM assay was able to detect and discriminate the five Plasmodium spp. with lowest detection limits of 1-100 copy numbers without nonspecific amplifications. The detection of Plasmodium spp. in clinical samples using this assay also achieved 100% concordance with that obtained using PlasmoNex(TM). This indicated that the diagnostic sensitivity and specificity of this assay in Plasmodium spp. detection is comparable with those of PlasmoNex(TM). The qRT-PCR-HRM assay is simple, produces results in two hours and enables high-throughput screening. Thus, it is an alternative method for rapid and accurate malaria diagnosis.
    Matched MeSH terms: DNA Copy Number Variations
  8. Fulltext Whole-genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome
    Ariffin H, Hainaut P, Puzio-Kuter A, Choong SS, Chan AS, Tolkunov D, et al.
    Proc Natl Acad Sci U S A, 2014 Oct 28;111(43):15497-501.
    PMID: 25313051 DOI: 10.1073/pnas.1417322111
    The Li-Fraumeni syndrome (LFS) and its variant form (LFL) is a familial predisposition to multiple forms of childhood, adolescent, and adult cancers associated with germ-line mutation in the TP53 tumor suppressor gene. Individual disparities in tumor patterns are compounded by acceleration of cancer onset with successive generations. It has been suggested that this apparent anticipation pattern may result from germ-line genomic instability in TP53 mutation carriers, causing increased DNA copy-number variations (CNVs) with successive generations. To address the genetic basis of phenotypic disparities of LFS/LFL, we performed whole-genome sequencing (WGS) of 13 subjects from two generations of an LFS kindred. Neither de novo CNV nor significant difference in total CNV was detected in relation with successive generations or with age at cancer onset. These observations were consistent with an experimental mouse model system showing that trp53 deficiency in the germ line of father or mother did not increase CNV occurrence in the offspring. On the other hand, individual records on 1,771 TP53 mutation carriers from 294 pedigrees were compiled to assess genetic anticipation patterns (International Agency for Research on Cancer TP53 database). No strictly defined anticipation pattern was observed. Rather, in multigeneration families, cancer onset was delayed in older compared with recent generations. These observations support an alternative model for apparent anticipation in which rare variants from noncarrier parents may attenuate constitutive resistance to tumorigenesis in the offspring of TP53 mutation carriers with late cancer onset.
    Matched MeSH terms: DNA Copy Number Variations/genetics
  9. Fulltext Genetically-defined novel oral squamous cell carcinoma cell lines for the development of molecular therapies
    Fadlullah MZ, Chiang IK, Dionne KR, Yee PS, Gan CP, Sam KK, et al.
    Oncotarget, 2016 May 10;7(19):27802-18.
    PMID: 27050151 DOI: 10.18632/oncotarget.8533
    Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC.
    Matched MeSH terms: DNA Copy Number Variations
  10. GENIPAC: A Genomic Information Portal for Head and Neck Cancer Cell Systems
    Lee BKB, Gan CP, Chang JK, Tan JL, Fadlullah MZ, Abdul Rahman ZA, et al.
    J Dent Res, 2018 07;97(8):909-916.
    PMID: 29512401 DOI: 10.1177/0022034518759038
    Head and neck cancer (HNC)-derived cell lines represent fundamental models for studying the biological mechanisms underlying cancer development and precision therapies. However, mining the genomic information of HNC cells from available databases requires knowledge on bioinformatics and computational skill sets. Here, we developed a user-friendly web resource for exploring, visualizing, and analyzing genomics information of commonly used HNC cell lines. We populated the current version of GENIPAC with 44 HNC cell lines from 3 studies: ORL Series, OPC-22, and H Series. Specifically, the mRNA expressions for all the 3 studies were derived with RNA-seq. The copy number alterations analysis of ORL Series was performed on the Genome Wide Human Cytoscan HD array, while copy number alterations for OPC-22 were derived from whole exome sequencing. Mutations from ORL Series and H Series were derived from RNA-seq information, while OPC-22 was based on whole exome sequencing. All genomic information was preprocessed with customized scripts and underwent data validation and correction through data set validator tools provided by cBioPortal. The clinical and genomic information of 44 HNC cell lines are easily assessable in GENIPAC. The functional utility of GENIPAC was demonstrated with some of the genomic alterations that are commonly reported in HNC, such as TP53, EGFR, CCND1, and PIK3CA. We showed that these genomic alterations as reported in The Cancer Genome Atlas database were recapitulated in the HNC cell lines in GENIPAC. Importantly, genomic alterations within pathways could be simultaneously visualized. We developed GENIPAC to create access to genomic information on HNC cell lines. This cancer omics initiative will help the research community to accelerate better understanding of HNC and the development of new precision therapeutic options for HNC treatment. GENIPAC is freely available at http://genipac.cancerresearch.my/ .
    Matched MeSH terms: DNA Copy Number Variations
  11. Fulltext Selective activation of miRNAs of the primate-specific chromosome 19 miRNA cluster (C19MC) in cancer and stem cells and possible contribution to regulation of apoptosis
    Nguyen PN, Huang CJ, Sugii S, Cheong SK, Choo KB
    J Biomed Sci, 2017 Mar 07;24(1):20.
    PMID: 28270145 DOI: 10.1186/s12929-017-0326-z
    BACKGROUND: The human chromosome 19 miRNA cluster (C19MC) of 43 genes is a primate-specific miRNA cluster that may have biological significance in the genetic complexity of the primate. Despite previous reports on individual C19MC miRNA expression in cancer and stem cells, systematic studies on C19MC miRNA expression and biological functions are lacking.

    RESULTS: Cluster-wide C19MC miRNA expression profiling by microarray analysis showed wholesome C19MC activation in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, in multipotent adipose-derived mesenchymal stem cells (MSCs) and a unipotent human white pre-adipocyte cell line, only selected C19MC miRNAs were expressed. MiRNA copy number analysis also showed selective C19MC expression in cancer cells with expression patterns highly similar to those in MSCs, suggesting similar miRNA regulatory mechanisms in these cells. Selective miRNA expression also suggests complex transcriptional mechanism(s) regulating C19MC expression under specific cellular and pathological conditions. Bioinformatics analysis showed that sixteen of the C19MC miRNAs share the same "AAGUGC" seed sequence with members of the miR-302/-372 family, which are known cellular reprogramming factors. In particular, C19MC-AAGUGC-miRNAs with the nucleotides 2-7 canonical seed position as in miR-302/-372 miRNAs, may play similar roles as miR-302/-372 in induced pluripotency. A biased 3p-arm selection of the C19MC-AAGUGC-miRNAs was observed indicating that targets of the 3p species of these miRNAs may be biologically significant in regulating stemness. Furthermore, bioinformatics analysis of the putative targets of the C19MC-AAGUGC-miRNAs predicted significant involvement of signaling pathways in reprogramming, many of which contribute to promoting apoptosis by indirect activation of the pro-apoptotic proteins BAK/BAX via suppression of genes of the cell survival pathways, or by enhancing caspase-8 activation through targeting inhibitors of TRAIL-inducing apoptosis.

    CONCLUSIONS: This work demonstrated selective C19MC expression in MSCs and cancer cells, and, through miRNA profiling and bioinformatics analysis, predicted C19MC modulation of apoptosis in induced pluripotency and tumorigenesis.

    Matched MeSH terms: DNA Copy Number Variations/genetics
  12. The emergence of the multi-species NIP1 effector in Rhynchosporium was accompanied by high rates of gene duplications and losses
    Mohd-Assaad N, McDonald BA, Croll D
    Environ Microbiol, 2019 08;21(8):2677-2695.
    PMID: 30838748 DOI: 10.1111/1462-2920.14583
    Plant pathogens secrete effector proteins to manipulate the host and facilitate infection. Cognate hosts trigger strong defence responses upon detection of these effectors. Consequently, pathogens and hosts undergo rapid coevolutionary arms races driven by adaptive evolution of effectors and receptors. Because of their high rate of turnover, most effectors are thought to be species-specific and the evolutionary trajectories are poorly understood. Here, we investigate the necrosis-inducing protein 1 (NIP1) effector in the multihost pathogen genus Rhynchosporium. We retraced the evolutionary history of the NIP1 locus using whole-genome assemblies of 146 strains covering four closely related species. NIP1 orthologues were present in all species but the locus consistently segregated presence-absence polymorphisms suggesting long-term balancing selection. We also identified previously unknown paralogues of NIP1 that were shared among multiple species and showed substantial copy-number variation within R. commune. The NIP1A paralogue was under significant positive selection suggesting that NIP1A is the dominant effector variant coevolving with host immune receptors. Consistent with this prediction, we found that copy number variation at NIP1A had a stronger effect on virulence than NIP1B. Our analyses unravelled the origins and diversification mechanisms of a pathogen effector family shedding light on how pathogens gain adaptive genetic variation.
    Matched MeSH terms: DNA Copy Number Variations
  13. Fulltext Insights into the genome structure and copy-number variation of Eimeria tenella
    Lim LS, Tay YL, Alias H, Wan KL, Dear PH
    BMC Genomics, 2012;13:389.
    PMID: 22889016 DOI: 10.1186/1471-2164-13-389
    Eimeria is a genus of parasites in the same phylum (Apicomplexa) as human parasites such as Toxoplasma, Cryptosporidium and the malaria parasite Plasmodium. As an apicomplexan whose life-cycle involves a single host, Eimeria is a convenient model for understanding this group of organisms. Although the genomes of the Apicomplexa are diverse, that of Eimeria is unique in being composed of large alternating blocks of sequence with very different characteristics - an arrangement seen in no other organism. This arrangement has impeded efforts to fully sequence the genome of Eimeria, which remains the last of the major apicomplexans to be fully analyzed. In order to increase the value of the genome sequence data and aid in the effort to gain a better understanding of the Eimeria tenella genome, we constructed a whole genome map for the parasite.
    Matched MeSH terms: DNA Copy Number Variations
  14. Fulltext Genome-Wide Computational Identification of Biologically Significant Cis-Regulatory Elements and Associated Transcription Factors from Rice
    Ho CL, Geisler M
    Plants (Basel), 2019 Oct 23;8(11).
    PMID: 31652796 DOI: 10.3390/plants8110441
    The interactions between transcription factors (TFs) and cis-acting regulatory elements (CREs) provide crucial information on the regulation of gene expression. The determination of TF-binding sites and CREs experimentally is costly and time intensive. An in silico identification and annotation of TFs, and the prediction of CREs from rice are made possible by the availability of whole genome sequence and transcriptome data. In this study, we tested the applicability of two algorithms developed for other model systems for the identification of biologically significant CREs of co-expressed genes from rice. CREs were identified from the DNA sequences located upstream from the transcription start sites, untranslated regions (UTRs), and introns, and downstream from the translational stop codons of co-expressed genes. The biologically significance of each CRE was determined by correlating their absence and presence in each gene with that gene's expression profile using a meta-database constructed from 50 rice microarray data sets. The reliability of these methods in the predictions of CREs and their corresponding TFs was supported by previous wet lab experimental data and a literature review. New CREs corresponding to abiotic stresses, biotic stresses, specific tissues, and developmental stages were identified from rice, revealing new pieces of information for future experimental testing. The effectiveness of some-but not all-CREs was found to be affected by copy number, position, and orientation. The corresponding TFs that were most likely correlated with each CRE were also identified. These findings not only contribute to the prioritization of candidates for further analysis, the information also contributes to the understanding of the gene regulatory network.
    Matched MeSH terms: DNA Copy Number Variations
  15. Rapid detection of α-thalassaemia variants using droplet digital PCR
    Lee TY, Lai MI, Ramachandran V, Tan JA, Teh LK, Othman R, et al.
    Int J Lab Hematol, 2016 Aug;38(4):435-43.
    PMID: 27349818 DOI: 10.1111/ijlh.12520
    INTRODUCTION: Alpha thalassaemia is a highly prevalent disease globally and is a well-known public health problem in Malaysia. The deletional forms of the mutation are the most common forms found in alpha thalassaemia. The three most common deletional alpha thalassaemia found in this region include --(SEA) deletion, -α(3.7) rightward and -α(4.2) leftward deletions. The prevalence rate of triplication alpha cases such as ααα(anti3.7) and ααα(anti4.2) is not known in Malaysia although it plays a role in exacerbating the clinical phenotypes in beta thalassaemia carriers. Recently, there have been more reported cases of rare alpha thalassaemia mutations due to the advancement of molecular techniques involved in thalassaemia detections. Therefore, it is essential to develop a new method which allows the detection of different alpha thalassaemia mutations including the rare ones simultaneously and accurately.

    METHODS: The purpose of this study was to design an assay for the detection of triplications, common and rare deletional alpha thalassaemia using droplet digital PCR (ddPCR).

    RESULTS: This is a quantitative detection method to measure the changes of copy number which can detect deletions, duplications and triplications of the alpha globin gene simultaneously.

    CONCLUSION: In conclusion, ddPCR is an alternative method for rapid detection of alpha thalassaemia variants in Malaysia.

    Matched MeSH terms: DNA Copy Number Variations
  16. Fulltext PanSNPdb: the Pan-Asian SNP genotyping database
    Ngamphiw C, Assawamakin A, Xu S, Shaw PJ, Yang JO, Ghang H, et al.
    PLoS One, 2011;6(6):e21451.
    PMID: 21731755 DOI: 10.1371/journal.pone.0021451
    The HUGO Pan-Asian SNP consortium conducted the largest survey to date of human genetic diversity among Asians by sampling 1,719 unrelated individuals among 71 populations from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, and Thailand. We have constructed a database (PanSNPdb), which contains these data and various new analyses of them. PanSNPdb is a research resource in the analysis of the population structure of Asian peoples, including linkage disequilibrium patterns, haplotype distributions, and copy number variations. Furthermore, PanSNPdb provides an interactive comparison with other SNP and CNV databases, including HapMap3, JSNP, dbSNP and DGV and thus provides a comprehensive resource of human genetic diversity. The information is accessible via a widely accepted graphical interface used in many genetic variation databases. Unrestricted access to PanSNPdb and any associated files is available at: http://www4a.biotec.or.th/PASNP.
    Matched MeSH terms: DNA Copy Number Variations/genetics
  17. Fulltext Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate
    Mohamad Shah NS, Sulong S, Wan Sulaiman WA, Halim AS
    Mol Genet Genomic Med, 2019 May;7(5):e635.
    PMID: 30924295 DOI: 10.1002/mgg3.635
    BACKGROUND: Nonsyndromic cleft lip and/or palate is one of the most common human birth defects worldwide that affects the lip and/or palate. The incidence of clefts varies among populations through ethnic, race, or geographical differences. The focus on Malay nonsyndromic cleft lip and/or palate (NSCL/P) is because of a scarce report on genetic study in relation to this deformity in Malaysia. We are interested to discuss about the genes that are susceptible to cause orofacial cleft formation in the family.

    METHODS: Genome-wide linkage analysis was carried out on eight large extended families of NSCL/P with the total of 91 individuals among Malay population using microarray platform. Based on linkage analyses findings, copy number variation (CNV) of LPHN2, SATB2, PVRL3, COL21A1, and TOX3 were identified in four large extended families that showed linkage evidence using quantitative polymerase chain reaction (qPCR) as for a validation purpose. Copy number calculated (CNC) for each genes were determined with Applied Biosystems CopyCallerTM Software v2.0. Normal CNC of the target sequence expected was set at two.

    RESULTS: Genome-wide linkage analysis had discovered several genes including TOX3 and COL21A1 in four different loci 4p15.2-p16.1, 6p11.2-p12.3, 14q13-q21, and 16q12.1. There was significant decreased, p number in extended families compared to the normal controls.

    CONCLUSION: Novel linkage evidence and significant low copy number of COL21A1 and TOX3 in NSCLP family was confirmed. These genes increased the risks toward NSCLP formation in that family traits.

    Matched MeSH terms: DNA Copy Number Variations
  18. Fulltext An alternate method for DNA and RNA extraction from clotted blood
    Zakaria Z, Umi SH, Mokhtar SS, Mokhtar U, Zaiharina MZ, Aziz AT, et al.
    Genet. Mol. Res., 2013;12(1):302-11.
    PMID: 23408417 DOI: 10.4238/2013.February.4.4
    We developed an alternative method to extract DNA and RNA from clotted blood for genomic and molecular investigations. A combination of the TRIzol method and the QIAamp spin column were used to extract RNA from frozen clotted blood. Clotted blood was sonicated and then the QIAamp DNA Blood Mini Kit was used for DNA extraction. Extracted DNA and RNA were adequate for gene expression analysis and copy number variation (CNV) genotyping, respectively. The purity of the extracted RNA and DNA was in the range of 1.8-2.0, determined by absorbance ratios of A(260):A(280). Good DNA and RNA integrity were confirmed using gel electrophoresis and automated electrophoresis. The extracted DNA was suitable for qPCR and microarrays for CNV genotyping, while the extracted RNA was adequate for gene analysis using RT-qPCR.
    Matched MeSH terms: DNA Copy Number Variations
  19. Fulltext Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
    Campa D, Barrdahl M, Santoro A, Severi G, Baglietto L, Omichessan H, et al.
    Breast Cancer Res, 2018 04 17;20(1):29.
    PMID: 29665866 DOI: 10.1186/s13058-018-0955-5
    BACKGROUND: Leukocyte telomere length (LTL) and mitochondrial genome (mtDNA) copy number and deletions have been proposed as risk markers for various cancer types, including breast cancer (BC).

    METHODS: To gain a more comprehensive picture on how these markers can modulate BC risk, alone or in conjunction, we performed simultaneous measurements of LTL and mtDNA copy number in up to 570 BC cases and 538 controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. As a first step, we measured LTL and mtDNA copy number in 96 individuals for which a blood sample had been collected twice with an interval of 15 years.

    RESULTS: According to the intraclass correlation (ICC), we found very good stability over the time period for both measurements, with ICCs of 0.63 for LTL and 0.60 for mtDNA copy number. In the analysis of the entire study sample, we observed that longer LTL was strongly associated with increased risk of BC (OR 2.71, 95% CI 1.58-4.65, p = 3.07 × 10- 4 for highest vs. lowest quartile; OR 3.20, 95% CI 1.57-6.55, p = 1.41 × 10- 3 as a continuous variable). We did not find any association between mtDNA copy number and BC risk; however, when considering only the functional copies, we observed an increased risk of developing estrogen receptor-positive BC (OR 2.47, 95% CI 1.05-5.80, p = 0.04 for highest vs. lowest quartile).

    CONCLUSIONS: We observed a very good correlation between the markers over a period of 15 years. We confirm a role of LTL in BC carcinogenesis and suggest an effect of mtDNA copy number on BC risk.

    Matched MeSH terms: DNA Copy Number Variations/genetics
  20. Identification of Copy Number Variation Among Nonsyndromic Cleft Lip and or Without Cleft Palate With Hypodontia: A Genome-Wide Association Study
    Ghazali N, Abd Rahman N, Ahmad A, Sulong S, Kannan TP
    Front Physiol, 2021;12:637306.
    PMID: 33732167 DOI: 10.3389/fphys.2021.637306
    Nonsyndromic cleft lip and or without cleft palate (NSCL/P) with the hypodontia is a common developmental abnormality in humans and animals. This study identified the genetic aberration involved in both NSCL/P and hypodontia pathogenesis. A cross-sectional study using genome-wide study copy number variation-targeted CytoScan 750K array carried out on salivary samples from 61 NSCL/P and 20 noncleft with and without hypodontia Malay subjects aged 7-13 years old. Copy number variations (CNVs) of SKI and fragile histidine triad (FHIT) were identified in NSCL/P and noncleft children using quantitative polymerase chain reaction (qPCR) as a validation analysis. Copy number calculated (CNC) for each gene determined with Applied Biosystems CopyCaller Software v2.0. The six significant CNVs included gains (12q14.3, 15q26.3, 1p36.32, and 1p36.33) and losses (3p14.2 and 4q13.2) in NSCL/P with hypodontia patients compared with the NSCL/P only. The genes located in these regions encoded LEMD3, IGF1R, TP73, SKI, FHIT, and UGT2β15. There were a significant gain and loss of both SKI and FHIT copy number in NSCL/P with hypodontia compared with the noncleft group (p < 0.05). The results supported that CNVs significantly furnish to the development of NSCL/P with hypodontia.
    Matched MeSH terms: DNA Copy Number Variations
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