Department Of Human Genetics And Molecular Medicine
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Item Genetics of idiopathic generalized epilepsy: An overview(Neurology Society of India, 2014) Prasad, D.K.V.; Satyanarayana, U.; Munshi, AnjanaIdiopathic generalized epilepsy (IGE) is a common type of epilepsy. Strong support for a genetic role in IGE comes from twin and family studies. Several subtypes of IGE have been reported but families often have members affected with different subtypes. Major advances have been made in the understanding of genetic basis of monogenic inherited epilepsies. However, most IGEs are complex genetic diseases and some susceptible IGE genes are shared across subtypes that determine subtypes in specific combinations. The high throughput technologies like deoxyribonucleic acid microarrays and sequencing technologies have the potential to identify causative genes or loci in non-familial cases.Item Analysis of pro‐ and anti‐inflammatory cytokine gene variants and serum cytokine levels as prognostic markers in breast cancer(Wiley, 2018) Kaur, Raman Preet; Vasudeva, Kanika; Singla, Heena; Benipal, Raja Paramjeet Singh; Khetarpal, Preeti; Munshi, AnjanaThe aim of current study was to evaluate the genetic variation in all the genes encoding pro‐ and anti‐inflammatory cytokines in association with breast cancer development in patients from Malwa region of Punjab. The importance of the levels of interleukin (IL)‐17, tumor necrosis factor, interferon γ, IL‐10, IL‐6, IL‐4, and IL‐2 with respect to clinicopathological data, prognosis, and disease‐free survival was also determined in these patients. Two hundred and fifty female breast cancer patients and 250 age‐matched controls were screened for variations in cytokine‐encoding genes using global screening array microchip and PCR‐RFLP. The level of cytokines was estimated in 150 patients and 60 age‐matched controls using BD™ Cytometric Bead Array (CBA) Human Th1/Th2/Th17 cytokine kit by BD Accuri flow cytometer. The difference in cytokine levels was evaluated by Mann–Whitney test. No significant variation in the genes encoding various cytokines was found between patients and controls. Out of the seven cytokines evaluated, the levels of IL‐6 and IL‐17a were found to be significantly high in patients in comparison with controls ( p = 0.001 and 0.02, respectively). The elevated levels of these cytokines are also associated significantly with poor outcome. We did not find any specific variation in the genes encoding various cytokines between patients and controls. However, there was a significant difference in the serum levels of IL‐6 and IL‐17a between patients and controls, and the elevated levels of these two cytokines associated significantly with poor outcome in breast cancer patients and, therefore, can be used as prognostic markers.Item Analysis of pro‐ and anti‐inflammatory cytokine gene variants and serum cytokine levels as prognostic markers in breast cancer(Wiley online Library, 2018) Kaur, R; P., Vasudeva, K.; Singla, H; Benipal, R. P. S; Khetarpal, Preeti; Munshi, AnjanaItem Association of BCL11A genetic variant (Rs11886868) with severityin β-thalassaemia major & sickle cell anaemia(Indian Council of Medical Research, 2016) Dadheech S.; Madhulatha D.; Jain S.; Joseph J.; Jyothy A.; Munshi, AnjanaBackground & objectives: The amount of foetal haemoglobin that persists in adulthood affects the clinical severity of haemoglobinopathies including ?-thalassaemia major and sickle cell anaemia (SCA). The present study was undertaken to analyse ?-thalassaemia as well as SCA patients for the single nucleotide polymorphism (SNP), rs11886868 (T/C) in BCL11A gene and to evaluate the association between this polymorphism and severity of ?-thalassaemia major and SCA. Methods: A total of 620 samples (420 ?-thalassaemia major and 200 SCA cases) were analysed before blood transfusion using basic screening tests like complete blood analysis and osmotic fragility and further confirmed by high performance liquid chromatography (HPLC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot blot techniques. All patients were transfusion dependent. Patients with ?-thalassaemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. ?-thalassaemia as well as SCA patients were analysed for the SNP, rs11886868 (T/C) in BCL11A gene and association between this polymorphism and severity of ?-thalassaemia major as well as SCA was evaluated. Results: There was a significant difference in genotypic and allelic frequencies of BCL11A gene polymorphism between mild and moderate and mild and severe cases in both the groups. A significant (P<0.001) difference was observed in the mean HbF levels between the three genotypes in different severity groups. HbF levels were found to be high in CC genotype bearing individuals followed by TC and TT in ?-thalassaemia major as well as SCA. Interpretation & conclusions: This study confirms that the T/C variant (rs11886868) of the BCL11A gene causing downregulation of BCL11A gene expression in adult erythroid precursors results in the induction of HbF and ameliorates the severity of ?-thalassaemia as well as SCA.Item Role of p53 gene in breast cancer: Focus on mutation spectrum and therapeutic strategies(Bentham Science Publishers B.V., 2018) Kaur, Raman Preet; Vasudeva, Kanika; Kumar, Roshan; Munshi, AnjanaTP53 is a tumor suppressor gene which is commonly mutated in various cancers including breast cancer. Alterations in the gene lead to an altered expression of various genes that are directly or indirectly under the transcriptional control of p53. This results in malfunctioning of DNA damage repair pathways, cell-cycle arrest, chromatin remodeling and apoptosis. Different mutations in TP53 gene have been reported in different ethnic groups and exon 4 and intron 3 are reported to be frequently mutated in breast cancer patients especially triple-negative breast cancer. Increased global burden of TP53 mutated breast tumors has paved the path for various therapies targeting p53/TP53. Numerous molecules including nutilins, MI series, RO5693, PRIMA-1, RITA, etc. have been developed. Majority of these restore p53/TP53 function by targeting negative regulators of p53/TP53, wtp53/TP53 (wild-type) and mtp53/TP53 (mutant). Most of these molecules are in the preclinical phase except for two APR-246 and COTI-2 that have progressed to clinical trials. The current review has been compiled with an aim to give an overview of mutations in p53 across various ethnic groups, the effect of these alterations on TP53 function and the therapeutic strategies developed till date targeting p53/TP53 especially in breast cancer.Item Apert's syndrome: Study by whole exome sequencing(Chongqing yi ke da xue, di 2 lin chuang xue yuan Bing du xing gan yan yan jiu suo, 2018) Munshi, Anjana; Khetarpal, Preeti; Das, Satrupa; Rao, Venkateshwar; Valecha, Monica; Bansal, Manita; Kumar, RoshanIn the present study we attempted a parent-child trio, whole exome sequencing (WES) approach to study Apert's syndrome. Clinical characteristics of the child were noted down and WES was carried out using Ion Torrent System that revealed the presence of previously reported P253R mutation in FGFR2 gene. Presence of two SNPs rs1047057 and rs554851880 in FGFR2 gene with an allelic frequency of 0.5113 and 0.001176 respectively and 161 complete damaging mutations were found. This study is the first reported case of exome sequencing approach on an Apert's syndrome patient aimed at providing better genetic counselling in a non-consanguineous relationship. - 2017 Chongqing Medical UniversityItem Apolipoprotein C3 gene polymorphisms in Southern Indian patients with nonalcoholic fatty liver disease(Springer, 2014) Munshi, AnjanaAim Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today. A previous study has suggested an association of apolipoprotein C3 (APOC3) gene variants with the risk of NAFLD in Asian Indian men living in the Western regions. The present study was carried out with an aim to evaluate the association of demographic features, serum lipid profile and APOC3 gene variants (C-482T and T-455C) NAFLD. Methods One hundred and fifty NAFLD patients and 150 age and gender-matched controls were included in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect the genotypes of APOC3. Serum lipid profile was analyzed. Results In the present study, body mass index was not a predictive demographic marker for NAFLD. Serum triglycerides were higher in patients (mean 155.95 ± 59.0) with NAFLD compared to the control group (mean 133.75 ± 44.71) (p = 0.016). APOC3 gene polymorphism T-455C (rs2854116) was significantly associated with NAFLD (p = 0.001). However, we did not find a significant association of C-482T polymorphism (rs2854117) of APOC3 gene with NAFLD. Genotype -455C/C of the SNP, rs2854116 associated significantly with the elevated serum triglycerides in patients. Conclusions The polymorphism T-455C in APOC3 gene and elevated serum triglycerides were associated with NAFLD.Item Time to Educate Physicians and Hospital Staff in Electronic Medical Records for Precision Medicine(Elsevier Inc., 2017) Sharma, S.; Munshi, Anjana; Sharma, V.Over the past decade, inexpensive and dense sequencing technologies have led to many genetic discoveries. Single nucleotide polymorphisms associated with over 250 different phenotypes have been identified by genome-wide association studies. Lack of large cohorts with adequately defined phenotypes has hindered further progress. This hindrance in genetic research can be overcome by electronic health records. These electronic health records have been recognized as a viable and efficient model for genetic research. The drawback of currently existing digitalized data and information in multiple unstructured formats continue to generate huge amount of information leading to difficulty in accessing invaluable and newly discovered knowledge. Connecting molecular data, individual genome sequence, patient phenotype, experimental data, and follow-up details is a big task. Road block to this monumental task of integration and interoperability are ethical, legal, and logistics. Data security and protection of patient rights are a must to maintain public support. In this chapter we have highlighted the advantages and challenges of using electronic health record data for genetic research as well as novel approaches and significant initiatives contributing toward precision medicine. ? 2017 Elsevier Inc.Item Role of TLR4 (C1196T) and CD14 (C-260T) Polymorphisms in Development of Ischemic Stroke, Its Subtypes and Hemorrhagic Stroke(Springer New York LLC, 2017) Das, Satrupa; Kaul, & Subhash; Jyothy, Akka; Munshi, AnjanaIn the present study, we evaluated the association of TLR4 and CD14 polymorphisms, i.e. C1196T and C-260T, respectively, with ischemic stroke (n?=?700), its subtypes and hemorrhagic stroke (n?=?300) in a South Indian population from Telangana. The genotypes were determined using PCR?RFLP, and the strength of association between genotypes and stroke was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. The results revealed a lack of association for TLR4 variant with ischemic stroke and hemorrhagic stroke, although a significant association was observed with the subtypes extracranial large artery (p?=?0.008), other determined aetiology (p?=?0.03) and undetermined aetiology (p?=?0.01). Investigations on the variant of CD14 gene revealed negative association among ischemic stroke patients; however, a significant association was observed for hemorrhagic stroke following dominant and recessive genotypic model (p?=?0.05, p?=?0.02). Among ischemic stroke subtype, a significant association was observed with intracranial large artery, extracranial large artery, other determined aetiology and undetermined aetiology form of stroke (p?Item Research advances in Apert syndrome(Elsevier B.V., 2018) Das, Satrupa; Munshi, AnjanaApert syndrome is one of the several genetic syndromes associated with craniosynostosis, a condition that includes premature fusion of one or multiple cranial sutures. There has been significant clinical variation among different sutural synostoses and also within particular suture synostosis. Enormous progress has been made in identifying various mutations associated with Apert Syndrome. Although a causal gene has been defined, the precise role of this mutation in producing craniofacial dysmorphology and other related abnormalities is in the process of discovery. Most of the understanding regarding this rare disorder has been possible due to mouse models that have helped in deciphering the elements of this rare human disease. Thus, molecular and cellular understanding of the disease has taken a leap and further with the advent of technology definitive diagnosis of the syndrome is no more of an issue. In this review, we have discussed and consolidated the possible molecular studies that have contributed in understanding of this rare syndrome. This article may help clinicians and researchers to inform about the latest progress in Apert syndrome. ? 2017