Institute of General Genetics and Cytology

Almaty, Kazakhstan

Institute of General Genetics and Cytology

Almaty, Kazakhstan

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Dulik M.C.,University of Pennsylvania | Zhadanov S.I.,University of Pennsylvania | Zhadanov S.I.,RAS Institute of Cytology and Genetics | Osipova L.P.,RAS Institute of Cytology and Genetics | And 8 more authors.
American Journal of Human Genetics | Year: 2012

The Altai region of southern Siberia has played a critical role in the peopling of northern Asia as an entry point into Siberia and a possible homeland for ancestral Native Americans. It has an old and rich history because humans have inhabited this area since the Paleolithic. Today, the Altai region is home to numerous Turkic-speaking ethnic groups, which have been divided into northern and southern clusters based on linguistic, cultural, and anthropological traits. To untangle Altaian genetic histories, we analyzed mtDNA and Y chromosome variation in northern and southern Altaian populations. All mtDNAs were assayed by PCR-RFLP analysis and control region sequencing, and the nonrecombining portion of the Y chromosome was scored for more than 100 biallelic markers and 17 Y-STRs. Based on these data, we noted differences in the origin and population history of Altaian ethnic groups, with northern Altaians appearing more like Yeniseian, Ugric, and Samoyedic speakers to the north, and southern Altaians having greater affinities to other Turkic speaking populations of southern Siberia and Central Asia. Moreover, high-resolution analysis of Y chromosome haplogroup Q has allowed us to reshape the phylogeny of this branch, making connections between populations of the New World and Old World more apparent and demonstrating that southern Altaians and Native Americans share a recent common ancestor. These results greatly enhance our understanding of the peopling of Siberia and the Americas. © 2012 The American Society of Human Genetics.


Badr H.A.,Zagazig University | AlSadek D.M.M.,Zagazig University | Mathew M.P.,Johns Hopkins University | Li C.-Z.,Florida International University | And 3 more authors.
Biomaterials | Year: 2015

Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that malignant cells experience during various stages of tumor development. This study investigated the response of nutrient-deprived cancer cells and their non-malignant counterparts to sialic acid supplementation and found that cells utilize negligible amounts of this sugar for energy. Instead cells use sialic acid to maintain cell surface glycosylation through complementary mechanisms. First, levels of key metabolites (e.g., UDP-GlcNAc and CMP-Neu5Ac) required for glycan biosynthesis are maintained or enhanced upon Neu5Ac supplementation. In concert, sialyltransferase expression increased at both the mRNA and protein levels, which facilitated increased sialylation in biochemical assays that measure sialyltransferase activity as well as at the whole cell level. In the course of these experiments, several important differences emerged that differentiated the cancer cells from their normal counterparts including resistant to sialic acid-mediated energy depletion, consistently more robust sialic acid-mediated glycan display, and distinctive cell surface vs. internal vesicle display of newly-produced sialoglycans. Finally, the impact of sialic acid supplementation on specific markers implicated in cancer progression was demonstrated by measuring levels of expression and sialylation of EGFR1 and MUC1 as well as the corresponding function of sialic acid-supplemented cells in migration assays. These findings both provide fundamental insight into the biological basis of sialic acid supplementation of nutrient-deprived cancer cells and open the door to the development of diagnostic and prognostic tools. © 2015 Elsevier Ltd.


Badr H.A.,Institute of General Genetics and Cytology | Badr H.A.,Florida International University | Badr H.A.,Zagazig University | Alsadek D.M.M.,Institute of General Genetics and Cytology | And 10 more authors.
Expert Review of Proteomics | Year: 2014

The nine FDA-approved protein biomarkers for the diagnosis and management of cancer are approaching maturity, but their different glycosylation compositions relevant to early diagnosis still remain practically unexplored at the sub-glycoproteome scale. Lectins generally exhibit strong binding to specific sub-glycoproteome components and this property has been quite poorly addressed as the basis for the early diagnosis methods. Here, we discuss some glycoproteome issues that make tackling the glycoproteome particularly challenging in the cancer biomarkers field and include a brief view for next generation technologies. © Informa UK, Ltd.


PubMed | Johns Hopkins University, Institute of General Genetics and Cytology, University of Maryland Baltimore County, Florida International University and Zagazig University
Type: | Journal: Biomaterials | Year: 2015

Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that malignant cells experience during various stages of tumor development. This study investigated the response of nutrient-deprived cancer cells and their non-malignant counterparts to sialic acid supplementation and found that cells utilize negligible amounts of this sugar for energy. Instead cells use sialic acid to maintain cell surface glycosylation through complementary mechanisms. First, levels of key metabolites (e.g., UDP-GlcNAc and CMP-Neu5Ac) required for glycan biosynthesis are maintained or enhanced upon Neu5Ac supplementation. In concert, sialyltransferase expression increased at both the mRNA and protein levels, which facilitated increased sialylation in biochemical assays that measure sialyltransferase activity as well as at the whole cell level. In the course of these experiments, several important differences emerged that differentiated the cancer cells from their normal counterparts including resistant to sialic acid-mediated energy depletion, consistently more robust sialic acid-mediated glycan display, and distinctive cell surface vs. internal vesicle display of newly-produced sialoglycans. Finally, the impact of sialic acid supplementation on specific markers implicated in cancer progression was demonstrated by measuring levels of expression and sialylation of EGFR1 and MUC1 as well as the corresponding function of sialic acid-supplemented cells in migration assays. These findings both provide fundamental insight into the biological basis of sialic acid supplementation of nutrient-deprived cancer cells and open the door to the development of diagnostic and prognostic tools.


PubMed | Johns Hopkins University, Institute of General Genetics and Cytology, University of Maryland Baltimore County, Florida International University and Zagazig University
Type: | Journal: Data in brief | Year: 2015

This report provides data that are specifically related to the differential sialylation of nutrient deprived breast cancer cells to sialic acid supplementation in support of the research article entitled, Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation [1]. Particularly, breast cancer cells, when supplemented with sialic acid under nutrient deprivation, display sialylated glycans at the cell surface, but non-malignant mammary cells show sialylated glycans intracellularly. The impact of sialic acid supplementation under nutrient deprivation was demonstrated by measuring levels of expression and sialylation of two markers, EGFR1 and MUC1. This Data in Brief article complements the main manuscript by providing detailed instructions and representative results for cell-level imaging and Western blot analyses of changes in sialylation during nutrient deprivation and sialic acid supplementation. These methods can be readily generalized for the study of many types of glycosylation and various glycoprotein markers through the appropriate selection of fluorescently-labeled lectins.


Djansugurova L.,Institute of General Genetics and Cytology | Zhunussova G.,Institute of General Genetics and Cytology | Zhunussova G.,University of Cape Town | Khussainova E.,Institute of General Genetics and Cytology | And 4 more authors.
Tumor Biology | Year: 2014

This study presents the first results of a molecular-genetic study of colorectal cancer (CRC) in Kazakhstan. Blood samples were collected from patients diagnosed with rectal or colon cancer (249 individuals) as well as a control cohort of healthy volunteers (245 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Combined analysis of data obtained from individuals of either Kazakh or Russian decent showed a significant association with increased CRC risk in the following genotypes: DCC (32008376G/G and G/A versus A/A; OR = 3.45, 95 % confidence interval (95 %CI) = 1.75–6.81, χ2 = 14.07, p < 0.0002), MLH1 (-93G/G versus G/A and A/A; OR = 1.45, 95 %CI = 1.02–2.07, χ2 = 4.21, p < 0.04), TP53 (Pro72Pro; OR = 3.80, 95 %CI = 2.46–5.88, χ2 = 61.27, p < 0.0001), combination GSTT1 deletions with heterozygotes versus normal homozygotes (OR = 1.43, 95 %CI = 1.00–2.04, χ2 = 3.90, p < 0.05), and GSTM1 deletions (OR = 1.83, 95 %CI = 1.28–2.63, χ2 = 11.04, p <.001). Analysis for ethnicity and smoking for each of the investigated polymorphisms showed that some genotypes can have a predictive value for susceptibility to CRC, at least those that demonstrate statistically significant ORs either for the combined mixed population of Kazakhstan or for both main ethnic groups separately (Kazakhs and Russians): TP53 Pro72Pro homozygous (for Kazakh—OR = 3.40, 95 %CI = 1.63–7.06, χ2 = 11.35, p < 0.003; for Russian—OR = 4.69, 95 %CI = 2.53–8.66, χ2 = 53.19, p < 0.0001) and GSTM1 deletions (for Kazakh—OR = 2.30, 95 %CI = 1.21–4.40, χ2 = 8.42, p < 0.01; for Russian—OR = 1.64, 95 %CI = 1.01–2.66, χ2 = 7.82, p < 0.02). © 2014, International Society of Oncology and BioMarkers (ISOBM).


Djansugurova L.B.,Institute of General Genetics and Cytology
Russian Journal of Developmental Biology | Year: 2011

Data on involvement of nitric oxide in apoptosis are contradictory. The balance between anti- and proapoptotic activities of nitric oxide depends on many factors, including its concentration in a tissue and interactions with other regulators of apoptosis. This paper describes the results of a series of experiments on the effect of nitric oxide donors and inhibitors as well as dNOS1 and dNOS4 transgenes on the apoptosis on drosophila Lobe RSV mutant strain and wild-type strain Oregon R. It has been shown that a high nitric oxide content in cells is able to inhibit antiapoptotic effect of HSP70 and stimulate apoptosis, possibly, via the grim-mediated apoptotic pathway. Moreover, long-term action of a high nitric oxide concentration during the entire development more efficiently stimulates the proapoptotic genes as compared with short-term action of this agent. © 2011 Pleiades Publishing, Ltd.


Zhunussova G.,Institute of General Genetics and Cytology | Zhunusbekova B.,Institute of General Genetics and Cytology | Djansugurova L.,Institute of General Genetics and Cytology
Clinical Laboratory | Year: 2015

Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide and the incidence is increasing in developed as well as developing countries including Kazakhstan. Glutathione S-transferases (GSTs) are considered to be cancer susceptibility genes as they play a role in the detoxification of carcinogenic species. In this case-control study the influence of GSTM1 and GSTT1 polymorphisms on CRC risk in Kazakhstan population were evaluated. Methods: Blood samples were collected from patients diagnosed with rectal or colon cancer (300 individuals) as well as a control cohort of healthy volunteers (300 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Deletion polymorphisms were genotyped employing a multiplex PCR amplification method. Association between polymorphisms and CRC susceptibility risk was calculated using multivariate analysis and logistic regression for odd ratio (OR). Results: The homozygous GSTM1 null genotype was associated with significantly increased risk of CRC (OR = 2.01, 95% CI = 1.45 - 2.79, p = 0.0001) while the homozygous GSST1 null genotype was not associated with the risk of developing CRC (OR = 1.10, 95% CI = 0.78-1.55, p = 0.001), but the heterozygous genotype correlated with CRC susceptibility (OR = 1.98, 95% CI = 1.30 - 3.00, p = 0.001). Also, separate analyses of each of the main ethnic groups (Kazakh and Russian) showed a strong association of GSTM1 null genotype with CRC risk (for Kazakhs OR = 2.36, 95% CI = 1.35 - 4.10, p = 0.006 and for Russians OR = 1.84, 95% CI = 1.17 - 2.89, p = 0.003). The CRC risk of GSTM1 null genotype in smokers was considerably higher (OR = 3.37, 95% CI = 1.78 - 6.38, p = 0.0007). The combination of the GSTM1 and GSTT1 null genotypes in combined mixed population of Kazakhstan showed a trend to increasing the risk of developing CRC (OR = 1.60,95% CI = 1.00 - 2.56), but it was not statistically significant. Conclusions: In conclusion, the results of this case-control study for sporadic cases of CRC show that GSTM1 deletion polymorphisms can have predictive value for susceptibility to CRC (OR = 2.01, p = 0.0001) for the mixed population from Kazakhstan and for both main ethnic groups (Kazakhs and Russians (OR = 2.36 and OR = 1.84, respectively)).


PubMed | Institute of General Genetics and Cytology
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2015

This study presents the first results of a molecular-genetic study of colorectal cancer (CRC) in Kazakhstan. Blood samples were collected from patients diagnosed with rectal or colon cancer (249 individuals) as well as a control cohort of healthy volunteers (245 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Combined analysis of data obtained from individuals of either Kazakh or Russian decent showed a significant association with increased CRC risk in the following genotypes: DCC (32008376G/G and G/A versus A/A; OR=3.45, 95% confidence interval (95%CI)=1.75-6.81, (2)=14.07, p<0.0002), MLH1 (-93G/G versus G/A and A/A; OR=1.45, 95%CI=1.02-2.07, (2)=4.21, p<0.04), TP53 (Pro72Pro; OR=3.80, 95%CI=2.46-5.88, (2)=61.27, p<0.0001), combination GSTT1 deletions with heterozygotes versus normal homozygotes (OR=1.43, 95%CI=1.00-2.04, (2)=3.90, p<0.05), and GSTM1 deletions (OR=1.83, 95%CI=1.28-2.63, (2)=11.04, p<.001). Analysis for ethnicity and smoking for each of the investigated polymorphisms showed that some genotypes can have a predictive value for susceptibility to CRC, at least those that demonstrate statistically significant ORs either for the combined mixed population of Kazakhstan or for both main ethnic groups separately (Kazakhs and Russians): TP53 Pro72Pro homozygous (for Kazakh-OR=3.40, 95%CI=1.63-7.06, (2)=11.35, p<0.003; for Russian-OR=4.69, 95%CI=2.53-8.66, (2)=53.19, p<0.0001) and GSTM1 deletions (for Kazakh-OR=2.30, 95%CI=1.21-4.40, (2)=8.42, p<0.01; for Russian-OR=1.64, 95%CI=1.01-2.66, (2)=7.82, p<0.02).


Djansugurova L.B.,Institute of General Genetics and Cytology | Perfilyeva A.V.,Institute of General Genetics and Cytology | Zhunusova G.S.,Institute of General Genetics and Cytology | Djantaeva K.B.,Institute of General Genetics and Cytology | And 2 more authors.
Frontiers in Genetics | Year: 2013

Aging associates with a variety of pathological conditions such as cancer, cardiovascular, neurodegenerative, autoimmune diseases, and metabolic disorders. The oncogenic alterations overlap frequently with the genes linked to aging. Here, we show that several aging related genes may serve as the genetic risk factors for cervical and esophagus cancers. In our study, we analyzed samples obtained from 115 patients with esophageal and 207 patients with cervical cancer. The control groups were selected to match the ethnicity and age of cancer patients. We examined the genes involved in the processes of xenobiotics detoxification (GSTM1 and GSTT1), DNA repair (XRCC1 and XRCC3), and cell cycle regulation and apoptosis (CCND1 and TP53). Our study revealed that deletions of GSTT1 and GSTM1 genes or the distinct point mutations of XRCC1 gene are associated with cervical and esophageal cancers. These results will lead to development of screening for detection of individuals susceptible to esophageal and cervical cancers. Introduction of the screening programs will allow the early and effective preventive measures that will reduce cancer incidence and mortality in Kazakhstan. © 2013 Djansugurova, Perfilyeva, Zhunusova, Djantaeva, Iksan and Khussainova.

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