ORCID Profile
0000-0002-7883-2515
Current Organisations
National Institutes of Health
,
Universiti Putra Malaysia
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Publisher: Elsevier BV
Date: 06-2016
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1038/GIM.2011.28
Abstract: Copy number variants are an important source of human genome ersity. The widespread distribution of hemizygous copy number variants in the DNA of healthy humans suggests that haploinsufficiency is largely tolerated. However, little is known about the extent to which corresponding nullizygosity (two-copy deletion) is similarly tolerated. We analyzed a cohort of first cousin unions to enrich for shared parental hemizygous events and tested their Mendelian inheritance in offspring. Analysis of autozygous DNA blocks (autozygome) in the offspring not only proved an efficient method of mapping "dispensable" DNA but also revealed potential selective bias against the occurrence of nullizygous changes. This bias was not restricted to genic copy number variants and was not accounted for by a high rate of miscarriages. The autozygome is an efficient way to map dispensable segments of DNA and may reveal selective bias against nullizygosity in healthy in iduals.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Wiley
Date: 12-10-2017
DOI: 10.1002/IJC.31076
Publisher: Springer Science and Business Media LLC
Date: 12-09-2012
DOI: 10.1007/S10875-012-9769-X
Abstract: Autosomal recessive hyper-IgE syndrome is a rare combined immunodeficiency characterized by susceptibility to viral infections, atopic eczema, high serum IgE and defective T cell activation. The genetic etiologies are erse. Null mutations in DOCK8 and TYK2 are responsible for many cases. This study aims to provide a detailed clinical and immunological characterization of the disease and explore the underlying genetic defects among a large series of patients followed by a single center. The available data might improve our understanding of the disease pathogenesis and prognosis. Clinical data of twenty-five patients diagnosed with AR-HIES were collected. Seventeen patients screened for STAT3, TYK2 and DOCK8 mutations. Sinopulmonary infections, dermatitis, hepatic disorders, cutaneous and systemic bacterial, fungal and viral infections were the most common clinical features. The rate of hepatic disorders and systemic infections were high. Twelve patients died with a median age of 10 years. CMV infection was the only statistically significant predicting factor for poor prognosis (early death). Three novel DOCK8 mutations and two large deletions were found in thirteen patients. No mutations found in STAT3 or TYK2 genes. Autosomal recessive hyper-IgE syndrome is a combined immunodeficiency disease characterized by high morbidity and mortality rate. The different genetic background and environmental factors may explain the more severe phenotypes seen in our series. DOCK8 defect is the most common identified genetic cause. Patients with no identified genetic etiology are likely to carry mutations in the regulatory elements of genes tested or in novel genes that are yet to be discovered.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JACI.2015.12.1310
Abstract: Molecular genetics techniques are an essential diagnostic tool for primary immunodeficiency diseases (PIDs). The use of next-generation sequencing (NGS) provides a comprehensive way of concurrently screening a large number of PID genes. However, its validity and cost-effectiveness require verification. We sought to identify and overcome complications associated with the use of NGS in a comprehensive gene panel incorporating 162 PID genes. We aimed to ascertain the specificity, sensitivity, and clinical sensitivity of the gene panel and its utility as a diagnostic tool for PIDs. A total of 162 PID genes were screened in 261 patients by using the Ion Torrent Proton NGS sequencing platform. Of the 261 patients, 122 had at least 1 known causal mutation at the onset of the study and were used to assess the specificity and sensitivity of the assay. The remaining s les were from unsolved cases that were biased toward more phenotypically and genotypically complicated cases. The assay was able to detect the mutation in 117 (96%) of 122 positive control subjects with known causal mutations. For the unsolved cases, our assay resulted in a molecular genetic diagnosis for 35 of 139 patients. Interestingly, most of these cases represented atypical clinical presentations of known PIDs. The targeted NGS PID gene panel is a sensitive and cost-effective diagnostic tool that can be used as a first-line molecular assay in patients with PIDs. The assay is an alternative choice to the complex and costly candidate gene approach, particularly for patients with atypical presentation of known PID genes.
Publisher: Cold Spring Harbor Laboratory
Date: 16-06-2020
DOI: 10.1101/2020.06.19.161976
Abstract: New carp hybrids are being developed for the aquaculture industry to support rising seafood demands. The present study was carried out to observe the changes in digestive tract, histology and functional capabilities of the new hybrid carp larvae for a better understanding of its digestive capability and the prediction of its best weaning time to a compound diet. A tubal digestive tract was elongated to the anus and buccal cavity by 3 DAH that coincided with the mouth opening and the start of exogenous feeding. A functional stomach was observed at 7 DAH with the relative gut index (RGI) of 10.7 ± 0.06. A layer of supranuclear protein was observed with lipoprotein at the outer layer of the digestive tract at 7 DAH. The morpho-histological results of this study indicated that hybrid Malaysian mahseer larvae should be able to digest, ingest and absorb an artificial diet beginning from 7 DAH. At this stage, the hybrid larvae could be gradually or perhaps totally weaned to an artificial diet of a suitable particle size.
Publisher: Oxford University Press (OUP)
Date: 22-03-2016
DOI: 10.1093/HMG/DDW087
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/542543
Abstract: Background . The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus Premier Pack has been designed to genotype 1936 gene variants thought to be essential for screening patients in personalized drug therapy. These variants include the cytochrome P450s (CYP450s), the key metabolizing enzymes, many other enzymes involved in phase I and phase II pharmacokinetic reactions, and signaling mediators associated with variability in clinical response to numerous drugs not only among in iduals, but also between ethnic populations. Materials and Methods . We genotyped 600 Saudi in iduals for 1936 variants on the DMET platform to evaluate their clinical potential in personalized medicine in ethnic Arabs. Results . Approximately 49% each of the 437 CYP450 variants, 56% of the 581 transporters, 56% of 419 transferases, 48% of the 104 dehydrogenases, and 58% of the remaining 390 variants were detected. Several variants, such as rs3740071, rs6193, rs258751, rs6199, rs11568421, and rs8187797, exhibited significantly either higher or lower minor allele frequencies (MAFs) than those in other ethnic groups. Discussion . The present study revealed some unique distribution trends for several variants in Arabs, which displayed partly inverse allelic prevalence compared to other ethnic populations. The results point therefore to the need to verify and ascertain the prevalence of a variant as a prerequisite for engaging it in clinical routine screening in personalized medicine in any given population.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2019
DOI: 10.1038/S41467-019-12283-6
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients ( F ROH ) for .4 million in iduals, we show that F ROH is significantly associated ( p 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of F ROH are confirmed within full-sibling pairs, where the variation in F ROH is independent of all environmental confounding.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2016
DOI: 10.1038/BJC.2016.188
Publisher: Wiley
Date: 22-07-2010
DOI: 10.1111/J.1399-0004.2010.01518.X
Abstract: Desmoplakin is an important cytoskeletal linker for the function of the desmosomes. Linking desmoplakin to certain types of cardiocutaneous syndromes has been a hot topic recently. Skin fragility-woolly hair syndrome is a rare autosomal recessive disorder involving the desmosomes and is caused by mutation in the desmoplakin gene (DSP). We report five members from a large family with skin fragility-woolly hair syndrome. The index is a 14-year-old girl with palmoplantar keratoderma, woolly hair, variable alopecia, dystrophic nails, and excessive blistering to trivial mechanical trauma. No cardiac symptoms were reported. Although formal cardiac examination was not feasible, the echocardiographic evaluation of the other two affected younger siblings was normal. Homozygosity mapping and linkage analysis revealed a high LOD score region in the short arm of chromosome 6 that harbors the DSP. Full sequencing of the DSP showed a novel homozygous c.7097 G>A (p.R2366H) mutation in all affected members, and the parents were heterozygous. This is the report of the third case/family of the skin fragility-woolly hair syndrome in the literature. We also present a clinical and molecular review of various desmoplakin-related phenotypes, with emphasis on onset of cardiomyopathy. The complexity of the desmoplakin and its variable presentations warrant introducing the term 'desmoplakinopathies' to describe all the phenotypes related to defects in the desmoplakin.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.EJMG.2012.10.003
Abstract: Hereditary Spastic Paraplegias (HSP) encompass a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by insidiously progressive weakness and spasticity of the lower extremities. We describe a consanguineous Saudi family segregating a complicated form of HSP in an autosomal recessive pattern. The two affected siblings had early onset, cognitive, speech and motor involvement with spasticity of the lower extremities. Their upper extremities were mildly hypertonic. An intronic splice acceptor site mutation in ERLIN2 was found to be responsible for causing this disorder found in this family. ERLIN2 is a mediator of endoplasmic reticulum degradation pathway (ERAD) which helps to remove the aberrant proteins. Our results, in concurrence with previous studies suggest that alteration in ERLIN2 is one of the causes of complicated HSP, thereby increasing the spectrum of known mutations in SPG18.
Publisher: Springer Science and Business Media LLC
Date: 26-06-2015
Publisher: Wiley
Date: 06-04-2017
DOI: 10.1002/IJC.30709
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.ATHEROSCLEROSIS.2015.11.019
Abstract: Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population. In this study, we performed a GWAS for CAD and myocardial infarction (MI) incidence in 5668 Saudis of Arab descent using the Affymetrix Axiom Genotyping platform. We describe SNPs at 16 loci that showed significant (P < 5 × 10(-8)) or suggestive GWAS association (P < 1 × 10(-5)) with CAD or MI, in the ethnic Saudi Arab population. Among the four variants reaching GWAS significance in the present study, the rs10738607_G [0.78(0.71-0.85) p = 2.17E-08] in CDNK2A/B gene was associated with CAD. Two other SNPs on the same gene, rs10757274_G [0.79(0.73-0.86) p = 2.98E-08] and rs1333045_C [0.79(0.73-0.86) p = 1.15E-08] as well as the rs9982601_T [1.38(1.23-1.55) p = 3.49E-08] on KCNE2 were associated with MI. These variants have been previously described in other populations. Several SNPs, including the rs7421388 (PLCL1) and rs12541758 (TRPA1) displaying a suggestive GWAS association (P < 1 × 10(-5)) with CAD as well as rs41411047 (RNF13), rs32793 (PDZD2) and rs4739066 (YTHDF3), similarly showing weak association with MI, were confirmed in an independent dataset. Furthermore, our estimation of heritability of CAD and MI based on observed genome-wide sharing in unrelated Saudi Arabs was approximately 33% and 44%, respectively. Our study has identified susceptibility variants for CAD/MI in ethnic Arabs. These findings provide further insights into pathways contributing to the susceptibility for CAD and will enable more comprehensive genetic studies of these diseases in Middle East populations.
Location: Saudi Arabia
No related grants have been discovered for SALMA WAKIL.