Displaying publications 1 - 20 of 455 in total

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  1. Fulltext Development of novel microsatellite markers using RAD sequencing technology for diversity assessment of rambutan (Nephelium lappaceum L.) germplasm
    Ab Razak S, Mad Radzuan S, Mohamed N, Nor Azman NHE, Abd Majid AM, Ismail SN, et al.
    Heliyon, 2020 Sep;6(9):e05077.
    PMID: 33024864 DOI: 10.1016/j.heliyon.2020.e05077
    The trend of microsatellite marker discovery and development revolved as a result of the advancement of next generation sequencing (NGS) technology as it has developed numerous microsatellites within a short period of time at a low cost. This study generated microsatellite markers using RAD sequencing technologies for the understudied Nephelium lappaceum. A total of 1403 microsatellite markers were successfully designed, which consisted of 853 di-, 525 tri-, 17 tetra-, 5 penta-, and 3 hexanucleotide microsatellite markers. Subsequently, selection of 39 microsatellites was made for the evaluation of genetic diversity of the selected 22 rambutan varieties. Twelve microsatellites, which exhibited high call rates across the samples, were used to assess the diversity of the aforementioned rambutan varieties. The analysis of 12 microsatellites revealed the presence of 72 alleles and six alleles per locus in average. Furthermore, the polymorphic information content (PIC) value ranged from 0.326 (NlaSSR20) to 0.832 (NlaSSR32), which included an average of 0.629 per locus, while the generated Neighbour Joining dendrogram showed two major clusters. The pairwise genetic distance of shared alleles exhibited a range of values from 0.046 (R134↔R170) to 0.818 (R5↔R170), which suggested highest dissimilarity detected between R5 and R170. Notably, these research findings would useful for varietal identification, proper management and conservation of the genetic resources, and exploitation and utilization in future breeding programs.
    Matched MeSH terms: Alleles
  2. Fulltext A rare FANCA gene variation as a breast cancer susceptibility allele in an Iranian population
    Abbasi S, Rasouli M
    Mol Med Rep, 2017 Jun;15(6):3983-3988.
    PMID: 28440412 DOI: 10.3892/mmr.2017.6489
    Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by congenital abnormalities, progressive bone marrow failure and Fanconi anemia complementation group A (FANCA) is also a potential breast and ovarian cancer susceptibility gene. A novel allele with tandem duplication of 13 base pair sequence in promoter region was identified. To investigate whether the 13 base pair sequence of tandem duplication in promoter region of the FANCA gene is of high penetrance in patients with breast cancer and to determine if the presence of the duplicated allele was associated with an altered risk of breast cancer, the present study screened DNA in blood samples from 304 breast cancer patients and 295 normal individuals as controls. The duplication allele had a frequency of 35.4 and 21.2% in patients with breast cancer and normal controls, respectively. There was a significant increase in the frequency of the duplication allele in patients with familial breast cancer compared with controls (45.1%, P=0.001). Furthermore, the estimated risk of breast cancer in individuals with a homozygote [odds ratio (OR), 4.093; 95% confidence intervals (CI), 1.957‑8.561] or heterozygote duplicated genotype (OR, 3.315; 95% CI, 1.996‑5.506) was higher compared with the corresponding normal homozygote genotype. In conclusion, the present study indicated that the higher the frequency of the duplicated allele, the higher the risk of breast cancer. To the best of our knowledge, the present study is the first to report FANCA gene duplication in patients with breast cancer.
    Matched MeSH terms: Alleles*
  3. Isolation and characterization of novel microsatellite loci for Asian sea bass, Lates calcarifer from genome sequence survey database
    Abdul Rahman Z, Choay-Hoong L, Mat Khairuddin R, Ab Razak S, Othman AS
    J Genet, 2012 Aug;91(2):e82-5.
    PMID: 22932425
    Matched MeSH terms: Alleles
  4. Genetic variability of oil palm parental genotypes and performance of its' progenies as revealed by molecular markers and quantitative traits
    Abdullah N, Rafii Yusop M, Ithnin M, Saleh G, Latif MA
    C. R. Biol., 2011 Apr;334(4):290-9.
    PMID: 21513898 DOI: 10.1016/j.crvi.2011.01.004
    Studies were conducted to assess the genetic relationships between the parental palms (dura and pisifera) and performance of their progenies based on nine microsatellite markers and 29 quantitative traits. Correlation analyses between genetic distances and hybrids performance were estimated. The coefficients of correlation values of genetic distances with hybrid performance were non-significant, except for mean nut weight and leaf number. However, the correlation coefficient of genetic distances with these characters was low to be used as predicted value. These results indicated that genetic distances based on the microsatellite markers may not be useful for predicting hybrid performance. The genetic distance analysis using UPGMA clustering system generated 5 genetic clusters with coefficient of 1.26 based on quantitative traits of progenies. The genotypes, DP16, DP14, DP4, DP13, DP12, DP15, DP8, DP1 and DP2 belonging to distant clusters and greater genetic distances could be selected for further breeding programs.
    Matched MeSH terms: Alleles
  5. Characterizing the genetic risk for type 2 diabetes in a Malaysian multi-ethnic cohort
    Abdullah N, Abdul Murad NA, Attia J, Oldmeadow C, Mohd Haniff EA, Syafruddin SE, et al.
    Diabet Med, 2015 Oct;32(10):1377-84.
    PMID: 25711284 DOI: 10.1111/dme.12735
    AIMS: To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project.
    METHODS: We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups.
    RESULTS: After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance.
    CONCLUSION: This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations.
    Study name: The Malaysian Cohort (TMC) project
    Matched MeSH terms: Alleles
  6. Fulltext A Novel Occulta-Type Spina Bifida Mediated by Murine Double Heterozygotes EphA2 and EphA4 Receptor Tyrosine Kinases
    Abdullah NL, Mohd-Zin SW, Ahmad-Annuar A, Abdul-Aziz NM
    Front Cell Dev Biol, 2017;5:105.
    PMID: 29312933 DOI: 10.3389/fcell.2017.00105
    Members of the Eph receptor tyrosine kinase have previously been implicated in cranial neural tube development. Failure of neural tube closure leads to the devastating conditions known as anencephaly and spina bifida. EphA2 and EphA4 are expressed at the tips of the closing spinal neural folds prior and during neural tube closure. We investigated the possible role of murine EphA2 and EphA4 during the last step of primary neural tube closure, which is adhesion and fusion. The individual mouse knockouts of EphA2 and EphA4 per se do not exhibit neural tube defects (NTDs). The embryos generated by the crossing of double heterozygotes Epha2tm1Jrui/+Epha4rb-2J/+ displayed NTDs with a wide degree of severity including close exencephaly and close spina bifida (spina bifida occulta). Interestingly, mutants displaying NTDs had skin covering the underlying lesion. The tissue sections revealed the elevated neural folds had not adhered and fused. The phenotypes seen in Epha2tm1Jrui/+Epha4rb-2J/+ double heterozygous embryos suggest both genes play a compensatory role with each other in the adhesion and fusion of the neural tube. In this study, there exists a >50% penetrance of NTDs in the mouse mutants, which genetically have a single allele each of EphA2 and EphA4 absent.
    Matched MeSH terms: Alleles
  7. Genotype-Phenotype Correlation of β-Thalassemia in Malaysian Population: Toward Effective Genetic Counseling
    Abdullah UYH, Ibrahim HM, Mahmud NB, Salleh MZ, Teh LK, Noorizhab MNFB, et al.
    Hemoglobin, 2020 May;44(3):184-189.
    PMID: 32586164 DOI: 10.1080/03630269.2020.1781652
    Effective prevention of β-thalassemia (β-thal) requires strategies to detect at-risk couples. This is the first study attempting to assess the prevalence of silent β-thal carriers in the Malaysian population. Hematological and clinical parameters were evaluated in healthy blood donors and patients with β-thal trait, Hb E (HBB: c.79G>A)/β-thal and β-thal major (β-TM). β-Globin gene sequencing was carried out for 52 healthy blood donors, 48 patients with Hb E/β-thal, 34 patients with β-TM and 38 patients with β-thal trait. The prevalence of silent β-thal carrier phenotypes found in 25.0% of healthy Malaysian blood donors indicates the need for clinician's awareness of this type in evaluating β-thal in Malaysia. Patients with β-TM present at a significantly younger age at initial diagnosis and require more blood transfusions compared to those with Hb E/β-thal. The time at which genomic DNA was extracted after blood collection, particularly from patients with β-TM and Hb E/β-thal, was found to be an important determinant of the quality of the results of the β-globin sequencing. Public education and communication campaigns are recommended as apparently healthy individuals have few or no symptoms and normal or borderline hematological parameters. β-Globin gene mutation characterization and screening for silent β-thal carriers in regions prevalent with β-thal are recommended to develop more effective genetic counseling and management of β-thal.
    Matched MeSH terms: Alleles
  8. Fulltext The spectrum of beta-thalassemia mutations in Malays in Singapore and Kelantan
    Abdullah WA, Jamaluddin NB, Kham SK, Tan JA
    Southeast Asian J. Trop. Med. Public Health, 1996 Mar;27(1):164-8.
    PMID: 9031421
    The spectrum of beta-thalassemia mutations in Malays in Singapore and Kelantan (Northeast Malaysia) was studied. Allele specific priming was used to determine the mutations in beta-carriers at -28, Codon 17, IVSI #1, IVSI #5, Codon 41-42 and IVSII #654 along the beta-globin gene. The most common structural hemoglobin variant in Southeast Asia, Hb E, was detected by DNA amplification with restriction enzyme (Mnl1) analysis. Direct genomic sequencing was carried out to detect the beta-mutations uncharacterized by allele-specific priming. The most prevalent beta-mutations in Singaporean Malays were IVSI #5 (45.83%) followed by Hb E (20.83%), codon 15 (12.5%) and IVSI #1 and IVSII #654 at 4.17% each. In contrast, the distribution of the beta-mutations in Kelantan Malays differed, with Hb E as the most common mutation (39.29%) followed by IVSI #5 (17.86%), codon 41-42 (14.29%), codon 19 (10.71%) and codon 17 (3.57%). The beta-mutations in Kelantan Malays follow closely the distribution of beta-mutations in Thais and Malays of Southern Thailand and Malays of West Malaysia. The AAC-->AGC base substitution in codon 19 has been detected only in these populations. The spectrum of beta-mutations in the Singaporean Malays is more similar to those reported in Indonesia with the beta-mutation at codon 15 (TGG-->TAG) present in both populations. The characterization of beta-mutations in Singaporean and Kelantan Malays will facilitate the establishment of effective prenatal diagnosis programs for beta-thalassemia major in this ethnic group.
    Matched MeSH terms: Alleles
  9. Studies on apolipoprotein(a) phenotypes. Part 1. Phenotype frequencies in a healthy Japanese population
    Abe A, Noma A
    Atherosclerosis, 1992 Sep;96(1):1-8.
    PMID: 1418098
    The frequency distribution for serum lipoprotein(a) (Lp(a)) concentrations in healthy Japanese was highly skewed, with a mean +/- S.D. of 14.6 +/- 13.6 mg/dl and a median of 11.0 mg/dl. The present study provides the first evidence on the frequencies of Lp(a) phenotypes and alleles in healthy Japanese subjects. There was a strong inverse relationship between the apparent molecular weights of apo(a) isoforms and plasma Lp(a) concentrations, as reported previously. However, because of the considerable overlap between the Lp(a) concentrations of the different phenotypes, it was impossible to predict Lp(a) concentration from Lp(a) phenotypes, or vice versa. The present results suggest that the distribution of Lp(a) concentrations, mean and median values and Lp(a) phenotype and allele frequencies in healthy Japanese are not significantly different from the results for Europeans, whereas they are significantly different from other Asian populations, i.e. Chinese, Indians and Malaysians.
    Matched MeSH terms: Alleles
  10. Fulltext Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects
    Ahmed RH, Huri HZ, Al-Hamodi Z, Salem SD, Al-Absi B, Muniandy S
    PLoS One, 2016;11(4):e0154369.
    PMID: 27111895 DOI: 10.1371/journal.pone.0154369
    BACKGROUND: Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV).

    METHOD: Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels.

    RESULTS: Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects.

    CONCLUSIONS: DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects.

    Matched MeSH terms: Alleles
  11. Fulltext Gene flow and genetic structure of Bactrocera carambolae (Diptera, Tephritidae) among geographical differences and sister species, B. dorsalis, inferred from microsatellite DNA data
    Aketarawong N, Isasawin S, Sojikul P, Thanaphum S
    Zookeys, 2015.
    PMID: 26798262 DOI: 10.3897/zookeys.540.10058
    The Carambola fruit fly, Bactrocera carambolae, is an invasive pest in Southeast Asia. It has been introduced into areas in South America such as Suriname and Brazil. Bactrocera carambolae belongs to the Bactrocera dorsalis species complex, and seems to be separated from Bactrocera dorsalis based on morphological and multilocus phylogenetic studies. Even though the Carambola fruit fly is an important quarantine species and has an impact on international trade, knowledge of the molecular ecology of Bactrocera carambolae, concerning species status and pest management aspects, is lacking. Seven populations sampled from the known geographical areas of Bactrocera carambolae including Southeast Asia (i.e., Indonesia, Malaysia, Thailand) and South America (i.e., Suriname), were genotyped using eight microsatellite DNA markers. Genetic variation, genetic structure, and genetic network among populations illustrated that the Suriname samples were genetically differentiated from Southeast Asian populations. The genetic network revealed that samples from West Sumatra (Pekanbaru, PK) and Java (Jakarta, JK) were presumably the source populations of Bactrocera carambolae in Suriname, which was congruent with human migration records between the two continents. Additionally, three populations of Bactrocera dorsalis were included to better understand the species boundary. The genetic structure between the two species was significantly separated and approximately 11% of total individuals were detected as admixed (0.100 ≤ Q ≤ 0.900). The genetic network showed connections between Bactrocera carambolae and Bactrocera dorsalis groups throughout Depok (DP), JK, and Nakhon Sri Thammarat (NT) populations. These data supported the hypothesis that the reproductive isolation between the two species may be leaky. Although the morphology and monophyly of nuclear and mitochondrial DNA sequences in previous studies showed discrete entities, the hypothesis of semipermeable boundaries may not be rejected. Alleles at microsatellite loci could be introgressed rather than other nuclear and mitochondrial DNA. Bactrocera carambolae may be an incipient rather than a distinct species of Bactrocera dorsalis. Regarding the pest management aspect, the genetic sexing Salaya5 strain (SY5) was included for comparison with wild populations. The SY5 strain was genetically assigned to the Bactrocera carambolae cluster. Likewise, the genetic network showed that the strain shared greatest genetic similarity to JK, suggesting that SY5 did not divert away from its original genetic makeup. Under laboratory conditions, at least 12 generations apart, selection did not strongly affect genetic compatibility between the strain and wild populations. This knowledge further confirms the potential utilization of the Salaya5 strain in regional programs of area-wide integrated pest management using SIT.
    Matched MeSH terms: Alleles
  12. Fulltext The Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD)
    Akkaif MA, Daud NAA, Sha'aban A, Ng ML, Abdul Kader MAS, Noor DAM, et al.
    Molecules, 2021 Apr 01;26(7).
    PMID: 33915807 DOI: 10.3390/molecules26071987
    Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2-81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.
    Matched MeSH terms: Alleles
  13. Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute Lymphoblastic Leukemia in a Yemeni Population
    Al-Absi B, Razif MFM, Noor SM, Saif-Ali R, Aqlan M, Salem SD, et al.
    Genet Test Mol Biomarkers, 2017 Oct;21(10):592-599.
    PMID: 28768142 DOI: 10.1089/gtmb.2017.0084
    BACKGROUND: Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent.

    METHODS: Seven single-nucleotide polymorphisms (SNPs) in IKZF1, three SNPs in DDC, two SNPs in CDKN2A, two SNPs in CEBPE, and three SNPs in LMO1 were genotyped in 289 Yemeni children (136 cases and 153 controls), using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Logistic regression analyses were used to estimate ALL risk, and the strength of association was expressed as odds ratios with 95% confidence intervals.

    RESULTS: We found that the IKZF1 SNP rs10235796 C allele (p = 0.002), the IKZF1 rs6964969 A>G polymorphism (p = 0.048, GG vs. AA), the CDKN2A rs3731246 G>C polymorphism (p = 0.047, GC+CC vs. GG), and the CDKN2A SNP rs3731246 C allele (p = 0.007) were significantly associated with ALL in Yemenis of Arab-Asian descent. In addition, a borderline association was found between IKZF1 rs4132601 T>G variant and ALL risk. No associations were found between the IKZF1 SNPs (rs11978267; rs7789635), DDC SNPs (rs3779084; rs880028; rs7809758), CDKN2A SNP (rs3731217), the CEBPE SNPs (rs2239633; rs12434881) and LMO1 SNPs (rs442264; rs3794012; rs4237770) with ALL in Yemeni children.

    CONCLUSION: The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.

    Matched MeSH terms: Alleles
  14. The Brain-Derived Neurotrophic Factor (BDNF) gene Val66Met (rs6265) polymorphism and stress among preclinical medical students in Malaysia
    Al-Hatamleh MAI, Hussin TMAR, Taib WRW, Ismail I
    J Taibah Univ Med Sci, 2019 Oct;14(5):431-438.
    PMID: 31728141 DOI: 10.1016/j.jtumed.2019.09.003
    Objective: This study aimed to determine the allelic and genotypic association of the Val66Met (rs6265) polymorphism in the BDNF gene with stress levels in preclinical medical students of Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia.

    Methods: In this cross-sectional study, we recruited all 122 preclinical medical students. The validated depression anxiety stress scales-21 (DASS-21) questionnaire was distributed and blood samples were collected from each subject for DNA extraction. Genotyping analysis of the BDNF gene (Val66Met) polymorphism was performed via an optimised polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

    Results: A total of 105 subjects agreed to participate in this study. Indian students were found to more likely have the Val/Val genotype, whereas Malay students were more likely to have the Met/Met genotype (p = 0.027). Individuals carrying any one of the three BDNF genotypes (Val/Val, Val/Met and Met/Met) differed significantly from each other in terms of their perception of stress (p = 0.010); students carrying the Val/Val genotype (M = 10.6) perceived significantly lower stress than students carrying the Val/Met (M = 14) and Met/Met (M = 15.1) genotypes.

    Conclusion: In our study, the Met-allele was associated with higher stress levels. To the best of our knowledge, this is the first study investigating this stress-related gene in medical students. The findings from this study should trigger more investigators to focus on the impact of stress on genetically predisposed medical students.

    Matched MeSH terms: Alleles
  15. Fulltext Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population
    Al-Herz W, Chou J, Delmonte OM, Massaad MJ, Bainter W, Castagnoli R, et al.
    Front Immunol, 2018;9:3146.
    PMID: 30697212 DOI: 10.3389/fimmu.2018.03146
    Objective: To present the genetic causes of patients with primary immune deficiencies (PIDs) in Kuwait between 2004 and 2017. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry. Genomic DNA from patients with clinical and immunological features of PID was sequenced using Sanger sequencing (SS), next generation sequencing (NGS) of targeted genes, whole exome sequencing (WES), and/or whole genome sequencing (WGS). Functional assays were utilized to assess the biologic effect of identified variants. Fluorescence in situ hybridization (FISH) for 22q11.2 deletion and genomic hybridizations arrays were performed when thymic defects were suspected. Results: A total of 264 patients were registered during the study period with predominance of patients with immunodeficiencies affecting cellular and humoral immunity (35.2%), followed by combined immunodeficiencies with associated syndromic features (24%). Parental consanguinity and family history suggestive of PID were reported in 213 (81%) and 145 patients (55%), respectively. Genetic testing of 206 patients resulted in a diagnostic yield of 70%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by in an autosomal recessive pattern. The majority of the mutations were missense mutations (57%) followed by deletions and frame shift mutations. Five novel disease-causing genes were discovered. Conclusions: Genetic testing should be an integral part in the management of primary immunodeficiency patients. This will help the delivery of precision medicine and facilitate proper genetic counseling. Studying inbred populations using sophisticated diagnostic methods can allow better understanding of the genetics of primary immunodeficiency disorders.
    Matched MeSH terms: Alleles
  16. Fulltext The suitability of P. falciparum merozoite surface proteins 1 and 2 as genetic markers for in vivo drug trials in Yemen
    Al-abd NM, Mahdy MA, Al-Mekhlafi AM, Snounou G, Abdul-Majid NB, Al-Mekhlafi HM, et al.
    PLoS One, 2013;8(7):e67853.
    PMID: 23861823 DOI: 10.1371/journal.pone.0067853
    The accuracy of the conclusions from in vivo efficacy anti-malarial drug trials depends on distinguishing between recrudescences and re-infections which is accomplished by genotyping genes coding P. falciparum merozoite surface 1 (MSP1) and MSP2. However, the reliability of the PCR analysis depends on the genetic markers' allelic diversity and variant frequency. In this study the genetic diversity of the genes coding for MSP1 and MSP2 was obtained for P. falciparum parasites circulating in Yemen.
    Matched MeSH terms: Alleles
  17. Fulltext Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome and stalled biogenesis of complex I
    Alahmad A, Nasca A, Heidler J, Thompson K, Oláhová M, Legati A, et al.
    EMBO Mol Med, 2020 11 06;12(11):e12619.
    PMID: 32969598 DOI: 10.15252/emmm.202012619
    Leigh syndrome is a progressive neurodegenerative disorder, most commonly observed in paediatric mitochondrial disease, and is often associated with pathogenic variants in complex I structural subunits or assembly factors resulting in isolated respiratory chain complex I deficiency. Clinical heterogeneity has been reported, but key diagnostic findings are developmental regression, elevated lactate and characteristic neuroimaging abnormalities. Here, we describe three affected children from two unrelated families who presented with Leigh syndrome due to homozygous variants (c.346_*7del and c.173A>T p.His58Leu) in NDUFC2, encoding a complex I subunit. Biochemical and functional investigation of subjects' fibroblasts confirmed a severe defect in complex I activity, subunit expression and assembly. Lentiviral transduction of subjects' fibroblasts with wild-type NDUFC2 cDNA increased complex I assembly supporting the association of the identified NDUFC2 variants with mitochondrial pathology. Complexome profiling confirmed a loss of NDUFC2 and defective complex I assembly, revealing aberrant assembly intermediates suggestive of stalled biogenesis of the complex I holoenzyme and indicating a crucial role for NDUFC2 in the assembly of the membrane arm of complex I, particularly the ND2 module.
    Matched MeSH terms: Alleles
  18. Genetic diversity analysis among collected purslane (Portulaca oleracea L.) accessions using ISSR markers
    Alam MA, Juraimi AS, Rafii MY, Hamid AA, Arolu IW, Abdul Latif M
    C. R. Biol., 2015 Jan;338(1):1-11.
    PMID: 25468001 DOI: 10.1016/j.crvi.2014.10.007
    Genetic diversity and relationships among 45 collected purslane accessions were evaluated using ISSR markers. The 28 primers gave a total of 167 bands, among which 163 were polymorphic (97.6%). The genetic diversity as estimated by Shannon's information index was 0.513, revealing a quite high level of genetic diversity in the germplasm. The average number of observed allele, effective allele, expected heterozygosity, polymorphic information content (PIC) and Nei's index were 5.96, 1.59, 0.43, 0.35 and 0.35, respectively. The UPGMA dendrogram based on Nei's genetic distance grouped the whole germplasm into 7 distinct clusters. The analysis of molecular variance (AMOVA) revealed that 89% of total variation occurred within population, while 11% were found among populations. Based on the constructed dendrogram using ISSR markers those accessions that are far from each other by virtue of genetic origin and diversity index (like Ac1 and Ac42; Ac19 and Ac45; Ac9 and Ac23; Ac18 and A25; Ac24 and Ac18) are strongly recommended to select as parent for future breeding program to develop high yielding and stress tolerant purslane variety in contribution to global food security.
    Matched MeSH terms: Alleles
  19. Fulltext Tracking origins and spread of sulfadoxine-resistant Plasmodium falciparum dhps alleles in Thailand
    Alam MT, Vinayak S, Congpuong K, Wongsrichanalai C, Satimai W, Slutsker L, et al.
    Antimicrob Agents Chemother, 2011 Jan;55(1):155-64.
    PMID: 20956597 DOI: 10.1128/AAC.00691-10
    The emergence and spread of drug-resistant Plasmodium falciparum have been a major impediment for the control of malaria worldwide. Earlier studies have shown that similar to chloroquine (CQ) resistance, high levels of pyrimethamine resistance in P. falciparum originated independently 4 to 5 times globally, including one origin at the Thailand-Cambodia border. In this study we describe the origins and spread of sulfadoxine-resistance-conferring dihydropteroate synthase (dhps) alleles in Thailand. The dhps mutations and flanking microsatellite loci were genotyped for P. falciparum isolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistant dhps alleles were fixed in Thailand, predominantly being the SGEGA, AGEAA, and SGNGA triple mutants and the AGKAA double mutant (mutated codons are underlined). These alleles had different geographical distributions. The SGEGA alleles were found mostly at the Burma border, while the SGNGA alleles occurred mainly at the Cambodia border and nearby provinces. Microsatellite data suggested that there were two major genetic lineages of the triple mutants in Thailand, one common for SGEGA/SGNGA alleles and another one independent for AGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) had AGKAA alleles with almost identical flanking microsatellites haplotypes. They were also identical at putatively neutral loci on chromosomes 2 and 3, suggesting a clonal nature of the parasite population in Yala. In summary, this study suggests multiple and independent origins of resistant dhps alleles in Thailand.
    Matched MeSH terms: Alleles
  20. Molecular markers associated with resistance to commonly used antimalarial drugs among Plasmodium falciparum isolates from a malaria-endemic area in Taiz governorate-Yemen during the transmission season
    Alareqi LMQ, Mahdy MAK, Lau YL, Fong MY, Abdul-Ghani R, Mahmud R
    Acta Trop, 2016 Oct;162:174-179.
    PMID: 27343362 DOI: 10.1016/j.actatropica.2016.06.016
    Since 2005, artesunate (AS) plus sulfadoxine/pyrimethamine (SP) combination has been adopted as the first-line treatment for uncomplicated malaria in Yemen in response to the high level of Plasmodium falciparum resistance to chloroquine (CQ). Therefore, the aim of the present study was to determine the frequency distribution of molecular markers associated with resistance to CQ and AS plus SP combination among P. falciparum isolates from a malaria-endemic area in Taiz governorate, Yemen. Fifty P. falciparum isolates were collected during a cross-sectional study in Mawza district, Taiz, in the period from October 2013 to April 2014. The isolates were investigated for drug resistance-associated molecular markers in five genes, including P. falciparum CQ resistance transporter (pfcrt) 76T and P. falciparum multidrug resistance 1 (pfmdr1) 86Y as markers of resistance to CQ, mutations in the Kelch 13 (K13) propeller domain for resistance to AS, and P. falciparum dihydrofolate reductase (pfdhfr) and P. falciparum dihydropteroate synthase (pfdhps) genes for resistance to SP. Nested polymerase chain reaction was used to amplify target genes in DNA extracts of the isolates followed by restriction fragment length polymorphism for detecting 76T and 86Y mutations in pfcrt and pfmdr1, respectively, and by DNA sequencing for detecting mutations in K13, pfdhfr and pfdhps. All the investigated isolates from Mawza district were harboring the pfcrt 76T mutant and the pfmdr1 N86 wild-type alleles. The pfdhfr 51I/108N double mutant allele was found in 2.2% (1/45) of the isolates; however, no mutations were detected at codons 436, 437, 540, 581 and 613 of pfdhps. All P. falciparum isolates that were successfully sequenced (n=47) showed the K13 Y493, R539, I543 and C580 wild-type alleles. In conclusion, the pfcrt 76T mutant allele is fixed in the study area about six years after the official withdrawal of CQ, possibly indicating its over-the-counter availability and continued use as a self-medication in the study area. However, the almost predominant wild-type alleles of the genes associated with resistance to AS and SP among P. falciparum isolates in the present study indicates the sustained efficacy of the currently adopted first-line treatment of AS plus SP in the study area.
    Matched MeSH terms: Alleles
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