Displaying publications 21 - 40 of 141 in total

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  1. SPTAN1 encephalopathy: distinct phenotypes and genotypes
    Tohyama J, Nakashima M, Nabatame S, Gaik-Siew C, Miyata R, Rener-Primec Z, et al.
    J Hum Genet, 2015 Apr;60(4):167-73.
    PMID: 25631096 DOI: 10.1038/jhg.2015.5
    Recent progress in genetic analysis reveals that a significant proportion of cryptogenic epileptic encephalopathies are single-gene disorders. Mutations in numerous genes for early-onset epileptic encephalopathies have been rapidly identified, including in SPTAN1, which encodes α-II spectrin. The aim of this review is to delineate SPTAN1 encephalopathy as a distinct clinical syndrome. To date, a total of seven epileptic patients with four different in-frame SPTAN1 mutations have been identified. The major clinical features of SPTAN1 mutations include epileptic encephalopathy with hypsarrhythmia, no visual attention, acquired microcephaly, spastic quadriplegia and severe intellectual disability. Brainstem and cerebellar atrophy and cerebral hypomyelination, as observed by magnetic resonance imaging, are specific hallmarks of this condition. A milder variant is characterized by generalized epilepsy with pontocerebellar atrophy. Only in-frame SPTAN1 mutations in the last two spectrin repeats in the C-terminal region lead to dominant negative effects and these specific phenotypes. The last two spectrin repeats are required for α/β spectrin heterodimer associations and the mutations can alter heterodimer formation between the two spectrins. From these data we suggest that SPTAN1 encephalopathy is a distinct clinical syndrome owing to specific SPTAN1 mutations. It is important that this syndrome is recognized by pediatric neurologists to enable proper diagnostic work-up for patients.
    Matched MeSH terms: Genetic Association Studies
  2. Fulltext SLC25A13 gene analysis in citrin deficiency: sixteen novel mutations in East Asian patients, and the mutation distribution in a large pediatric cohort in China
    Song YZ, Zhang ZH, Lin WX, Zhao XJ, Deng M, Ma YL, et al.
    PLoS One, 2013;8(9):e74544.
    PMID: 24069319 DOI: 10.1371/journal.pone.0074544
    The human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet.
    Matched MeSH terms: Genetic Association Studies
  3. SCN1A IVS5N+5 polymorphism and response to sodium valproate: a multicenter study
    Haerian BS, Baum L, Tan HJ, Kwan P, Raymond AA, Saruwatari J, et al.
    Pharmacogenomics, 2012 Oct;13(13):1477-85.
    PMID: 23057548 DOI: 10.2217/pgs.12.127
    Approximately 30% of epilepsy patients do not response to antiepileptic drugs (AEDs). The functional SCN1A IVS5N+5 polymorphism may play a role in response to some AEDs. The purpose of this study was to examine this hypothesis in a cohort study of Malaysian and Hong Kong Chinese epilepsy patients on sodium valproate (VPA) monotherapy and in a meta-analysis.
    Matched MeSH terms: Genetic Association Studies
  4. Rubinstein-Taybi syndrome in diverse populations
    Tekendo-Ngongang C, Owosela B, Fleischer N, Addissie YA, Malonga B, Badoe E, et al.
    Am J Med Genet A, 2020 12;182(12):2939-2950.
    PMID: 32985117 DOI: 10.1002/ajmg.a.61888
    Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p 
    Matched MeSH terms: Genetic Association Studies
  5. Role of the Serine/Threonine Kinase 11 (STK11) or Liver Kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome
    Altamish M, Dahiya R, Singh AK, Mishra A, Aljabali AAA, Satija S, et al.
    Crit Rev Eukaryot Gene Expr, 2020;30(3):245-252.
    PMID: 32749111 DOI: 10.1615/CritRevEukaryotGeneExpr.2020033451
    Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. PJS is an autosomal prevailing disease, due to genetic mutation on chromosome 19p, manifested by restricted mucocutaneous melanosis in association with gastrointestinal (GI) polyposis. The gene for PJS has recently been shown to be a serine/threonine kinase, known as LKB1 or STK11, which maps to chromosome subband 19p13.3. This gene has a putative coding region of 1302 bp, divided into nine exons, and acts as a tumor suppressor in the hamartomatous polyps of PJS patients and in the other neoplasms that develop in PJS patients. It is probable that these neoplasms develop from hamartomas, but it remains possible that the LKB1 or STK11 locus plays a role in a different genetic pathway of tumor growth in the cancers of PJS patients. This article focuses on the role of LKB1 or STK11 gene expression in PJS and related cancers.
    Matched MeSH terms: Genetic Association Studies
  6. Fulltext Review of functional markers for improving cooking, eating, and the nutritional qualities of rice
    Lau WC, Rafii MY, Ismail MR, Puteh A, Latif MA, Ramli A
    Front Plant Sci, 2015;6:832.
    PMID: 26528304 DOI: 10.3389/fpls.2015.00832
    After yield, quality is one of the most important aspects of rice breeding. Preference for rice quality varies among cultures and regions; therefore, rice breeders have to tailor the quality according to the preferences of local consumers. Rice quality assessment requires routine chemical analysis procedures. The advancement of molecular marker technology has revolutionized the strategy in breeding programs. The availability of rice genome sequences and the use of forward and reverse genetics approaches facilitate gene discovery and the deciphering of gene functions. A well-characterized gene is the basis for the development of functional markers, which play an important role in plant genotyping and, in particular, marker-assisted breeding. In addition, functional markers offer advantages that counteract the limitations of random DNA markers. Some functional markers have been applied in marker-assisted breeding programs and have successfully improved rice quality to meet local consumers' preferences. Although functional markers offer a plethora of advantages over random genetic markers, the development and application of functional markers should be conducted with care. The decreasing cost of sequencing will enable more functional markers for rice quality improvement to be developed, and application of these markers in rice quality breeding programs is highly anticipated.
    Matched MeSH terms: Genetic Association Studies
  7. Fulltext Resolving the ancestry of Austronesian-speaking populations
    Soares PA, Trejaut JA, Rito T, Cavadas B, Hill C, Eng KK, et al.
    Hum Genet, 2016 Mar;135(3):309-26.
    PMID: 26781090 DOI: 10.1007/s00439-015-1620-z
    There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion.
    Matched MeSH terms: Genetic Association Studies
  8. Resistance gene cloning from a wild crop relative by sequence capture and association genetics
    Arora S, Steuernagel B, Gaurav K, Chandramohan S, Long Y, Matny O, et al.
    Nat Biotechnol, 2019 02;37(2):139-143.
    PMID: 30718880 DOI: 10.1038/s41587-018-0007-9
    Disease resistance (R) genes from wild relatives could be used to engineer broad-spectrum resistance in domesticated crops. We combined association genetics with R gene enrichment sequencing (AgRenSeq) to exploit pan-genome variation in wild diploid wheat and rapidly clone four stem rust resistance genes. AgRenSeq enables R gene cloning in any crop that has a diverse germplasm panel.
    Matched MeSH terms: Genetic Association Studies
  9. Fulltext Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen
    Joyce-Tan SM, Zain SM, Abdul Sattar MZ, Abdullah NA
    J Diabetes Res, 2016;2016:2161376.
    PMID: 26682227 DOI: 10.1155/2016/2161376
    Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15-3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.
    Matched MeSH terms: Genetic Association Studies
  10. Fulltext Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy
    Boon-Peng H, Mat Jusoh JA, Marshall CR, Majid F, Danuri N, Basir F, et al.
    PLoS One, 2016;11(3):e0148755.
    PMID: 26930585 DOI: 10.1371/journal.pone.0148755
    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs) contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV) were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the "foetal cardiac gene programme" which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability.
    Matched MeSH terms: Genetic Association Studies
  11. Fulltext Progesterone Receptor (PGR) gene polymorphism is associated with susceptibility to preterm birth
    Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z
    BMC Med Genet, 2015;16:63.
    PMID: 26286601 DOI: 10.1186/s12881-015-0202-1
    Preterm birth (PTB) is the major cause of death in newborn and the second major cause of death in children less than 5 years old worldwide. Genetic polymorphism has been implicated as a factor for the occurrence of preterm birth. The aim of this study is to evaluate whether polymorphism in the progesterone receptor (PGR) is associated with susceptibility to preterm birth.
    Matched MeSH terms: Genetic Association Studies
  12. Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry
    Wen W, Shu XO, Guo X, Cai Q, Long J, Bolla MK, et al.
    Breast Cancer Res, 2016 12 08;18(1):124.
    PMID: 27931260
    BACKGROUND: Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry.

    METHODS: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk.

    RESULTS: We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P 

    Matched MeSH terms: Genetic Association Studies*
  13. Polymorphisms of the resistin gene and their association with obesity and resistin levels in Malaysian Malays
    Apalasamy YD, Rampal S, Salim A, Moy FM, Su TT, Majid HA, et al.
    Biochem Genet, 2015 Jun;53(4-6):120-31.
    PMID: 25991560 DOI: 10.1007/s10528-015-9678-9
    Single nucleotide polymorphisms (SNP) in the resistin gene (RETN) are linked to obesity and resistin levels in various populations. However, results have been inconsistent. This study aimed to investigate association between polymorphisms in the resistin gene with obesity in a homogenous Malaysian Malay population. This study is also aimed to determine association between resistin levels with certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were included in this study and genotyping was carried out using Sequenom MassARRAY. There was no significant difference found in both allelic and genotype frequencies of each of the RETN SNPs between the obese and non-obese groups after Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly associated with log-resistin levels. The GG genotype carriers are found to have higher levels of log-resistin compared to A allele carriers. The RETN haplotypes (CAG, CGA and GA) were significantly associated with resistin levels. However, the haplotypes of the RETN gene were not associated with obesity. Resistin levels were not correlated to metabolic parameters such as body weight, waist circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes are of apparent functional importance in the regulation of resistin levels but are not correlated with obesity and related markers.
    Matched MeSH terms: Genetic Association Studies*
  14. Polymorphic variant Ser128Arg of E-Selectin is associated with breast cancer risk and high grade tumors
    Naidu R, Har YC, Taib NA
    Onkologie, 2011;34(11):592-7.
    PMID: 22104155 DOI: 10.1159/000334060
    The present study aimed to evaluate the association between the E-Selectin Ser128Arg polymorphism and breast cancer risk and clinicopathological characteristics of the patients.
    Matched MeSH terms: Genetic Association Studies
  15. Fulltext Phenotype-genotype analyses of clinically diagnosed Malaysian familial hypercholestrolemic patients
    Al-Khateeb A, Al-Talib H, Mohamed MS, Yusof Z, Zilfalil BA
    Adv Clin Exp Med, 2013 Jan-Feb;22(1):57-67.
    PMID: 23468263
    BACKGROUND: Familial hypercholesterolemia and familial defective apo lipoprotein B are genetic disorders caused by defects in the low-density lipoprotein receptor gene and apo lipoprotein B 100 genes, respectively. The clinical phenotype of both diseases is characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol, tendinous xanthomata, and premature coronary heart disease.
    OBJECTIVES: The aim of this study is to perform an association study between different gene sequence variants in low-density lipoprotein and apo lipoprotein B 100 genes to the clinical finding and lipid profile parameters of the study subjects.
    MATERIAL AND METHODS: A group of 164 familial hypercholesterolemic patients were recruited. The promoter region, exon 2-15 of the low density lipoprotein gene and parts of exon 26 and 29 of apo lipoprotein B 100 gene were screened by Denaturating Gradient High Performance Liquid Chromatography.
    RESULTS: For the apo lipoprotein B 100 gene, those with apo lipoprotein B 100 gene mutation have a significantly higher frequency of cardiovascular disease (P = 0.045), higher low density lipoprotein cholesterol and total cholesterol: high density lipoprotein cholesterol ratio than those without mutation (P = 0.03 and 0.02, respectively). For the low density lipoprotein gene defect those with frame shift mutation group showed the worst clinical presentation in terms of low density lipoprotein cholesterol level and cardiovascular frequency.
    CONCLUSIONS: There was a statistically significant association between mutations of low density lipoprotein gene and apo lipoprotein B 100 genes and history of cardiovascular disease, younger age of presentation, family history of hyperlipidemia, tendon xanthoma and low density lipoprotein cholesterol level.
    Study site: Cardiology Clinic, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia
    Matched MeSH terms: Genetic Association Studies*
  16. Patterns of linkage disequilibrium at PARK16 may explain variances in genetic association studies
    Li H, Teo YY, Tan EK
    Mov Disord, 2015 Sep;30(10):1335-42.
    PMID: 25758099 DOI: 10.1002/mds.26176
    Reproducing genomewide association studies findings in different populations is challenging, because the reproducibility fundamentally relies on the similar patterns of linkage disequilibrium between the unknown causal variants and the genotyped single-nucleotide polymorphisms (SNPs).
    Matched MeSH terms: Genetic Association Studies*
  17. PARK16 is associated with PD in the Malaysian population
    Gopalai AA, Ahmad-Annuar A, Li HH, Zhao Y, Lim SY, Tan AH, et al.
    Am J Med Genet B Neuropsychiatr Genet, 2016 09;171(6):839-47.
    PMID: 27174169 DOI: 10.1002/ajmg.b.32454
    PARK16 was identified as a risk factor for Parkinson's disease in a Japanese cohort; however, subsequent studies in the other populations including the Chinese, European, Caucasian, and Chilean have shown a protective role instead. To investigate this locus in our Malaysian cohort, 1,144 individuals were screened for five SNPs in the PARK16 locus and logistic regression analysis showed that the A allele of the rs947211 SNP reduced the risk of developing PD via a recessive model (Odds ratio 0.57, P-value 0.0003). Pooled analysis with other Asian studies showed that A allele of the rs947211 SNP decreased the risk of developing PD via a recessive model (Odds ratio 0.71, P-value 0.0001). In addition, when meta-analysis was performed with other Asian population, three SNPs (rs823128, rs823156, and rs11240572) reduced risk of developing PD via a dominant model. © 2016 Wiley Periodicals, Inc.
    Matched MeSH terms: Genetic Association Studies
  18. On the critical importance of meticulous data extraction for meta-analysis of genetic association study
    Low TY, Chin KY, Tan SC
    Arch Physiol Biochem, 2023 Dec;129(4):1007-1008.
    PMID: 33689514 DOI: 10.1080/13813455.2021.1890132
    Matched MeSH terms: Genetic Association Studies
  19. Nonsynonymous polymorphisms of the PDLIM5 gene association with the occurrence of both bipolar disorder and schizophrenia
    Zain MA, Roffeei SN, Zainal NZ, Kanagasundram S, Mohamed Z
    Psychiatr Genet, 2013 Dec;23(6):258-61.
    PMID: 24064681 DOI: 10.1097/YPG.0000000000000015
    Two single nucleotide polymorphisms of PDLIM5, rs7690296 and rs11097431, were genotyped using Mass-Array SNP genotyping by Sequenom technology in 244 bipolar disorder patients, 471 schizophrenia patients, and 601 control individuals who were Malay, Chinese, and Indian ethnic groups in the Malaysian population. A significant association was observed in allele frequency between the rs7690296 polymorphism and bipolar disorder in the Indian ethnic group [P=0.02, adjusted odds ratio (OR) 0.058, 95% confidence interval (CI) 0.36-0.93]. A significant association was also observed between the rs7690296 polymorphism and schizophrenia under the recessive model for both Malay (P=0.02, adjusted OR 1.86, 95% CI 1.12-3.10) and Indian (P=0.02, adjusted OR 1.92, 95% CI 1.10-3.37) ethnic groups. However, no association was detected between the rs11097431 polymorphism either with bipolar disorder or with schizophrenia. Therefore, it can be deduced that the nonsynonymous rs7690296 polymorphism could play an important role in the pathophysiology of both bipolar disorder and schizophrenia.
    Matched MeSH terms: Genetic Association Studies*
  20. Fulltext No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing
    Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, et al.
    J Med Genet, 2016 May;53(5):298-309.
    PMID: 26921362 DOI: 10.1136/jmedgenet-2015-103529
    BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction.

    METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia.

    RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75).

    CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.

    Matched MeSH terms: Genetic Association Studies
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