Papers by Said Al-yahyaee
Microbiology, Dec 1, 1995
Unlike the CytA toxin from native Bacillus thuringiensis subsp. israelensis (Bti) crystals, the i... more Unlike the CytA toxin from native Bacillus thuringiensis subsp. israelensis (Bti) crystals, the inclusions of cloned CytA produced by Bti IPS 78/11 in the presence of the 20 kDa 'helper' protein require a reducing agent in addition to a highly alkaline pH for complete solubilization. Activation of the solubilized CytA with a range of proteases produced 25-22 kDa products. SDS-PAGE analysis and N-terminal amino acid sequencing revealed that CytA was processed very similarly at both termini by proteinase K or by Anopheles or Culex gut extracts. Trypsin, by contrast, processed CytA predominantly at the N-terminus. In w i t r o cytolytic assays against Aedes aegypti cells, and haemolytic assays against rat erythrocytes, showed that CytA processed at both termini by proteinase K was the most active form. Thus CytA, like other Bt G-endotoxins, is processed to a well-defined protease-resistant product and this processing enhances the toxicity in vitro and possibly in vivo.
Scientific Reports
Global Developmental Delay/Intellectual disability (ID) is the term used to describe various diso... more Global Developmental Delay/Intellectual disability (ID) is the term used to describe various disorders caused by abnormal brain development and characterized by impairments in cognition, communication, behavior, or motor skills. In the past few years, whole-exome sequencing (WES) has been proven to be a powerful, robust, and scalable approach for candidate gene discoveries in consanguineous populations. In this study, we recruited 215 patients affected with ID from 118 Middle Eastern families. Whole-exome sequencing was completed for 188 individuals. The average age at which WES was completed was 8.5 years. Pathogenic or likely pathogenic variants were detected in 32/118 families (27%). Variants of uncertain significance were seen in 33/118 families (28%). The candidate genes with a possible association with ID were detected in 32/118 (27%) with a total number of 64 affected individuals. These genes are novel, were previously reported in a single family, or cause strikingly differen...
Journal of Pediatric Genetics
Next-generation sequencing, such as whole-exome sequencing (WES), is increasingly used in the stu... more Next-generation sequencing, such as whole-exome sequencing (WES), is increasingly used in the study of Mendelian disorders, yet many are reported as “negative.” Inappropriate variant annotation and filtering steps are reasons for missing the molecular diagnosis. Noncoding variants, including splicing mutations, are examples of variants that can be overlooked. Herein, we report a family of four affected newborns, and all presented with severe congenital microcephaly. Initial research WES analysis identified a damaging homozygous variant in NME1 gene as a possible cause of primary microcephaly phenotype in these patients. However, reanalysis of the exome data uncovered a biallelic splice site variant in asparagine synthetase gene which seems to be the possible cause of the phenotype in these patients. This study highlights the importance of revisiting the exome data and the issue of “negative” exome and the afterward approaches to identify and prove new candidate genes.
Genome Biology and Evolution
Variation in genes involved in the absorption, distribution, metabolism, and excretion of drugs (... more Variation in genes involved in the absorption, distribution, metabolism, and excretion of drugs (ADME) can influence individual response to a therapeutic treatment. The study of ADME genetic diversity in human populations has led to evolutionary hypotheses of adaptation to distinct chemical environments. Population differentiation in measured drug metabolism phenotypes is, however, scarcely documented, often indirectly estimated via genotype-predicted phenotypes. We administered seven probe compounds devised to target six cytochrome P450 enzymes and the P-glycoprotein (P-gp) activity to assess phenotypic variation in four populations along a latitudinal transect spanning over Africa, the Middle East, and Europe (349 healthy Ethiopian, Omani, Greek, and Czech volunteers). We demonstrate significant population differentiation for all phenotypes except the one measuring CYP2D6 activity. Genome-wide association studies (GWAS) evidenced that the variability of phenotypes measuring CYP2B6...
World Journal of Diabetes, 2015
To investigate the association of 10 known common gene variants with susceptibility to type 2 dia... more To investigate the association of 10 known common gene variants with susceptibility to type 2 diabetes mellitus (T2D) among Omanis. Using case-control design, a total of 992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped, by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system, for the following gene variants: KCNJ11 (rs5219), TCF7L2 (rs7903146), CDKAL1 (rs10946398), CDKN2A/B (rs10811661), FTO (rs9939609 and rs8050136), IGF2BP2 (rs4402960), SLC30A8 (rs13266634) CAPN10 (rs3792267) and HHEX (rs1111875). T2D patients were recruited from the Diabetes Clinic (n = 243) and inpatients (n = 749) at Sultan Qaboos Univesity Hospital (SQUH), Muscat, Oman. Adult control participants (n = 294) were volunteers from the community and from those visiting Family Medicine Clinic at SQU, for regular medical checkup. The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study. Almost all volunteers questioned had a relative with diabetes mellitus. Inspite of the small number of normoglycemic controls in this study, this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of ≥ 1.3 reaching at least 80% power. Data was collected from June 2010 to February 2012. Using binary logistic regression analysis, four gene variants showed significant association with T2D risk: KCNJ11 (rs5219, P = 5.8 × 10(-6), OR = 1.74), TCF7L2 (rs7903146, P = 0.001, OR = 1.46), CDKAL1 (rs10946398, P = 0.002, OR = 1.44) and CDKN2A/B (rs10811661, P = 0.020, OR = 1.40). The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls {[KCNJ11 (rs5219), P < 0.001], [TCF7L2 (rs7903146), P…
Public Health Genomics, 2005
Objective: To establish a suitable human model for the study of the genetics of complex diseases.... more Objective: To establish a suitable human model for the study of the genetics of complex diseases. Methods: We have selected an Omani Arab population to provide the statistical power required to study the genetics of complex diseases with confidence. This model consists of five multigenerational highly inbred pedigrees, descending from a small number of founders just a few generations ago with environmental homogeneity, restricted geographical distribution, detailed records and well-ascertained and -validated pedigrees. Stringent criteria were adopted for defining the phenotypes of hypertension, diabetes mellitus, dyslipidemias and obesity. The SOLAR genetic software package was used to draw the pedigree structure. Results: Outstanding statistical power to detect susceptibility loci was obtained. Conclusions: This model represents a large homogeneous human family-based population for the study of genetic and environmental factors contributing to complex diseases.
Obesity, 2007
The objective was to examine the circadian changes in blood pressure and their relation to the me... more The objective was to examine the circadian changes in blood pressure and their relation to the metabolic syndrome and its components in Omani Arabs. Ambulatory blood pressure (ABPM) was recorded in 1124 subjects from 5 large, extended, consanguineous, and young Arab pedigrees. According to the International Diabetes Federation's definition, 264 subjects had the metabolic syndrome, a prevalence of 23%. Subjects were defined as non-dippers when their nocturnal systolic blood pressure (SBP) fell by <10% from daytime SBP. Non-dippers with the metabolic syndrome were 131 of 264 (50%), compared with 265 of 860 (31%) without the metabolic syndrome. Of the non-dippers, 99 of 131 (76%) were females and 32 of 131 (24%) were males. Daytime and nighttime SBP and DBP and nighttime pulse pressure were significantly higher in non-dipper subjects with the metabolic syndrome. The important determinants of a non-dipping BP in this cohort were high BMI and high serum triglycerides. We hypothesize that obesity and nocturnal volume-dependent hypertension may be involved in the pathophysiology of non-dipping in the metabolic syndrome. This study showed that non-dipping BP was common in subjects with the metabolic syndrome. Higher 24-hour blood pressure load may add to the indices of the overall cardiovascular burden already associated with the metabolic syndrome.
Neurology, 2006
Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity... more Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present. At least 22 genetic loci have been linked to HSP, 8 of which are autosomal recessive (ARHSP). HSP complicated with the presence of thin corpus callosum (HSP-TCC) is a common subtype of HSP. One genetic locus has been identified on chromosome 15q13-q15 (SPG11) for HSP-TCC, but some HSP-TCC families have not been linked to this locus. The authors characterized two families clinically and radiologically and performed a genome-wide scan and linkage analysis. The two families had complicated ARHSP. The affected individuals in Family A had thin corpus callosum and mental retardation, whereas in Family B two of three affected individuals had epilepsy. In both families linkage analysis identified a locus on chromosome 8 between markers D8S1820 and D8S532 with the highest combined lod score of 7.077 at marker D8S505. This 9 cM interval located on 8p12-p11.21 represents a new locus for ARHSP-TCC. Neuregulin and KIF13B genes, located within this interval, are interesting functional candidate genes for this HSP form. Two consanguineous families with complicated autosomal recessive hereditary spastic paraplegia were clinically characterized and genetically mapped to a new locus on 8p12-p11.21.
Medical Principles and Practice, 2005
Objective: To estimate the apolipoprotein E (apo E) allele distribution in the Omani population a... more Objective: To estimate the apolipoprotein E (apo E) allele distribution in the Omani population and to compare them with those of other populations. Subjects and Methods: One hundred and sixty-two healthy Omanis of Arab Bedouin origin were genotyped by polymerase chain reaction followed by restriction fragment length polymorphism. Results: The apo E allele frequencies were: ε2, 0.052; ε3, 0.886; ε4, 0.062. This pattern of distribution, characterized by the lowest ε4 and among the highest ε3 allele frequencies in the world, was very similar to that of Arabs, Southern Europeans of the Mediterranean basin, Indians, and Japanese populations. Conclusion: The results indicate that the allelic distribution of apo E in healthy Omanis is characterized by low Apo ε4 and high ε3 allele frequencies similar to those of other Arab, Southern European, Japanese and Indian populations. The homogeneous distribution of apo E alleles in this group of populations might have been influenced by diet and/o...
Lipids in Health and Disease, 2007
Introduction: Lipoprotein(a) is an independent risk factor for Ischaemic Heart Disease (IHD) in t... more Introduction: Lipoprotein(a) is an independent risk factor for Ischaemic Heart Disease (IHD) in the general population. There are conflicting reports in the extent of its association with IHD among subjects with Type 2 diabetes mellitus (T2DM). The aim was to determine the concentration of Lp(a) and its relationship with other lipids parameters among Omani T2DM subjects with and without IHD. An overnight fasting blood sample from 221 T2DM subjects (86 females and 135 males) and 156 non-diabetics (69 females and 87 males) aged 30-70 years (as control) was taken for lipid profile studies. Results: Lp(a) was significantly lower (p = 0.012) among T2DM subjects 0.123(1.12) g/L compared to non-diabetics 0.246 (1.18)g/L, irrespective of gender. A significant correlation (Spearman correlation, P = 0.047) was revealed between Lp(a) and IHD among Omani T2DM subjects. The proportions of T2DM subjects with IHD and an Lp(a) >0.3 g/L was higher compared to T2DM without IHD irrespective of gender, for women 42% vs. 27% and for men 17.5 vs. 8%, respectively. A significant negative correlation existed between Lp(a) and triglycerides (r = 0.41, P = 0.002) among T2DM subjects. In contrast, a significant positive correlation existed between Lp(a) and LDL-chol among the non-diabetic subjects. Women had significantly higher Lp(a) concentration compared to men (0.30 Vs. 0.16 g/L, P < 0.0001) irrespective of the diabetic status. Conclusion: Lp(a) is an independent risk factor for IHD among Omani T2DM subjects. Lp(a) concentration was significantly lower and negatively correlated with triglycerides among Omani diabetic compared to non-diabetic subjects.
Lipids in Health and Disease, 2007
Background: ApolipoproteinA1(apoA1) is the major apoprotein constituent of high-densitylipoprotei... more Background: ApolipoproteinA1(apoA1) is the major apoprotein constituent of high-densitylipoprotein(HDL). The relationship of apoA1-75 bp(M1-) allele polymorphism with lipoprotein phenotype and cardiovascular diseae (CVD) remain unclear. Overnight fasting blood samples were collected from a cohort of high-risk Omani population, 90 non-diabetic subjects and 149 type 2 diabetes mellitus (T2DM) subjects for genotype and phenotype studies. Results: The M1+ and M1-alleles frequencies were 0.808 and 0.192 for M1+ and M1-, respectively, comparable to the frequency of apoA1 (M1+ and M1-) amongst a healthy Omani population, 0.788 and 0.212, respectively. The frequencies of the hetero-and homozygous subjects for the MspI polymorphism at-75 (M1-) of the apoA1 gene were in Hardy-Weinberg equilibrium. The mean Lp(a) concentration was significantly higher(P = 0.02) in subjects carrying M1allele compared to M1 + allele of the APOA1 gene with an odd ratio of 2.3(95% CI, 1.13-14.3), irrespective of gender and the diabetic status. Conclusion: ApolipoproteinA1-75 G/A (M1-) polymorphism is relatively common and is positively associated with Lp(a) and therefore, may confer a potential risk for cardiovascular disease (CVD).
Journal of Hypertension, 2004
Journal of Clinical Lipidology, 2009
Human Biology, 2004
The relative frequencies of the *A allele of the APOA1 gene at -75 bp (M1-) and the C or T +83/+ ... more The relative frequencies of the *A allele of the APOA1 gene at -75 bp (M1-) and the C or T +83/+ 84 bp allele (M2-) varied significantly between populations. We found the frequencies of M1- and M2- to be 0.22 and 0.067, respectively, in 150 healthy Omanis. These frequencies were compared to frequencies found in other world populations.
Gene, 2013
Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim ... more Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value=0.001), waist circumference (p-value=0.037), BMI (p-value=0.015) and percentage of total body fat (p-value=0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.
cags.org.ae
... Riad Bayoumi1, Saeed Al-Yahyaee1, Sulayma Albarwani2, Deepali Jaju2, Anthony Comuzzie3, Juan ... more ... Riad Bayoumi1, Saeed Al-Yahyaee1, Sulayma Albarwani2, Deepali Jaju2, Anthony Comuzzie3, Juan Lopez-Alvarenga3, Mohammed Hassan2 1Department of Biochemistry and 2Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University ...
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Papers by Said Al-yahyaee