The allele frequency estimates of these STR markers reveal that alleles are not equally distribut... more The allele frequency estimates of these STR markers reveal that alleles are not equally distributed in all the three populations included in the study.
2014 USNC-URSI Radio Science Meeting (Joint with AP-S Symposium), 2014
Magnetic stimulation is an evolving, non-invasive neural stimulation technology used for clinical... more Magnetic stimulation is an evolving, non-invasive neural stimulation technology used for clinical applications, including brain mapping, treatment of mood disorders, epilepsy, and chronic pain. Based on the induction principle, magnetic stimulation induces electric fields in the conductive tissue due to the time-varying current in the magnetic coil. It requires the magnetic coil to be in close proximity to the stimulation site to produce neural activation. The stimulation threshold of magnetic stimulation depends on the magnitude and the pulse width of the induced electric field. Traditionally, the efficacy of the magnetic stimulation is studied using analytical formulations based on the coil parameters and operating conditions (Roth, B. J. et. al., IEEE TBME 1990). Several studies were performed to include the tissue boundaries in the simulation model of the induced electric field (Nagarajan, S.S. et al., IEEE TBME 1996). However, these models were over simplified and do not include the tissue heterogeneity found in the nerve bundle.
Short Tandem Repeat (STR) loci are widely considered to be effective for variety of applications ... more Short Tandem Repeat (STR) loci are widely considered to be effective for variety of applications including forensic applications, phylogenetic reconstruction and chimerism based post Haematopoietic Stem Cell Transplantation (HSCT) graft monitoring. For each application, specific sets of STR loci are used. In the present study, we have attempted to use same set of STR loci for varied purposes based on their efficacy and informativity. Population and patient based study. We have analyzed 5 STR loci--vWA, Tho1, FES, F13 and TPOX in 1000 North Indians. All five markers were also analyzed for chimerism based graft monitoring after HSCT in 42 HLA matched pair of patient-donor to predict the outcome of transplantation. The analysis was done for Hardy Weinberg equilibrium (HWE), Heterozygosity, Polymorphism information content (PIC) and Power of Exclusion and Phylogenetic assessment. High allelic variability in term of Heterozygosity (0.68-0.76), PIC (0.66-0.74) and high Power of exclusion ...
Forensic Short Tandem Repeat (STR) loci are effective for the purpose of individual identificatio... more Forensic Short Tandem Repeat (STR) loci are effective for the purpose of individual identification, and other forensic applications. Most of these markers have high allelic variability and mutation rate because of which they have limited use in the phylogenetic reconstruction. In the present study, we have carried out a meta-analysis to explore the possibility of using only five STR loci (TPOX, FES, vWA, F13A and Tho1) to carry out phylogenetic assessment based on the allele frequency profile of 20 world population and north Indian Hindus analyzed in the present study. Phylogenetic analysis based on two different approaches - genetic distance and maximum likelihood along with statistical bootstrapping procedure involving 1000 replicates was carried out. The ensuing tree topologies and PC plots were further compared with those obtained in earlier phylogenetic investigations. The compiled database of 21 populations got segregated and finely resolved into three basal clusters with very...
The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions... more The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1) is an important component of RAS which determines the vasoactive peptide Angiotensin-II. In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8) and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease d...
Human genome sequencing results revealed an insight into the role of human genetic variation behi... more Human genome sequencing results revealed an insight into the role of human genetic variation behind differential susceptibility of human diseases, differential response to pharmacological agents and presence of varied phenotypes. This leads to the concept of personalized medicine. In the present review we have discussed the objectives and approaches for carrying out pharmacogenomics and pharmacogenetics studies. The review also incorporates the major findings categorizing the common diseases on the basis of genetic profiles and ethnic information and in establishing personalized disease diagnosis, drug responses and treatment modalities based on the genetic determinants. Overall an attempt has been made to highlight the importance of studying the genetic profiles of an individual in biomedical and pharmacogenomics research.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2014
Efficacy of magnetic stimulation of the central or peripheral nervous system depends on the spati... more Efficacy of magnetic stimulation of the central or peripheral nervous system depends on the spatial and temporal distribution of the induced electric field generated by the magnetic coil. Therefore, accurate estimation of the induced electric field is crucial to the design and optimization of magnetic coils, particularly as the coil dimensions are reduced. In this work, we developed a numerical model of a multifascicular sciatic nerve to study the effect of tissue heterogeneity on the induced electric field. Using a multi-resolution electric field solver, we can resolve feature sizes as small as 1μm, allowing inclusion of the nerve membrane and the myelination layer. Preliminary results indicate that fascicle distribution and axons' proximity to each other significantly affect the magnitude and distribution of the induced electric field as compared to traditional homogeneous tissue models for field simulation.
Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells... more Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells against reactive oxygen species and plays a vital role in phase II of biotransformation of many substances. Overexpression of GST (EC 2.5.1.18) has been documented in the erythrocytes of patients with chronic renal failure, which may be of clinical relevance. Keeping this background in mind, we have investigated the relationship between human GST gene polymorphism in end stage renal disease (ESRD) patients. We have assessed 184 patients with ESRD and 569 age-and sex-matched controls from North India. The GSTT1 and GSTM1 null genotypes were identified by polymerase chain reaction (PCR). GSTP1-313 A/G mutation was determined by PCR followed by restriction enzyme digestion. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphism were evaluated. We observed that GSTM1 null genotype was present in 46.74% of the ESRD patients while GSTT1 null genotype was present in 58.7% of the ESRD subjects. The genotypic distribution of GSTP1 was Ile(105)/Ile(105) in 47.3%, Ile(105)/Val(105) in 30.97% and Val(105)/Val(105) in 21.74% of ESRD patients. There was a significant association of null alleles of the GSTM1 (p = 0.0386; OR = 1.445, 95% CI = 1.033-2.021) and GSTT1 (p < or = 0.0001; OR = 4.568, 95% CI = 3.215-6.492) and in the -313 G alleles (Val) of the GSTP1 gene (p = 0.0032; OR = 1.956, 95% CI = 1.265-3.024) with end stage renal disease. The combined analysis of the three genotypes showed a further increased risk to ESRD (p < or = 0.0001; OR = 9.01, 95% CI = 5.55-14.626). The null / low polymorphism of the detoxifying enzymes GSTT1, GSTM1, and GSTP1 are associated with the risk of developing ESRD in North Indian patients.
Renal allograft rejection or dysfunction often results in graft failure, and remains the major ob... more Renal allograft rejection or dysfunction often results in graft failure, and remains the major obstacle in the success of renal transplantation. Various immunological and nonimmunological factors are involved in allograft rejection. In addition to human leukocyte antigen loci, several genetically controlled molecules have been identified in recent years as playing important roles in the process of rejection. Genetic variants in genes encoding different T-helper (Th) type 1 and Th2 cytokines, chemokines and their receptors, growth factors, molecules of the renin-angiotensin system, enzymes of the homocysteine pathway, and proteins acting as substrates of immunosuppressive drugs impact on the success of engraftment and highlight the concept of genetic predisposition to allograft rejection. This review evaluates specific genetic variants and their functional roles in graft failure, with an emphasis on the latest methodologies available for genotyping, and appropriate strategies to enable them to become a tool of predictive and individualized medicine to ensure better transplant outcome.
Page 1. J Forensic Sci, July 2004, Vol. 49, No. 4 Paper ID JFS2004129 Published 26 May 2004 Avail... more Page 1. J Forensic Sci, July 2004, Vol. 49, No. 4 Paper ID JFS2004129 Published 26 May 2004 Available online at: www.astm.org FOR THE RECORD Faisal Khan,1 M.Sc.; Atul Kr. Pandey,1 M.Sc.; Manorama Tripathi,1 M.Sc ...
ApoB3&amp... more ApoB3' hyper variable region is one of the highly polymorphic genetic marker and reveals a high degree of allelic variation in different populations therefore; it can be a useful marker for different clinical tests in which individual differences at DNA level form the basis of detection. In the present study we compared Apo B3 HVR with other 28 STR markers at allele frequency level, heterozygosity, polymorphism information content (PIC) and power of exclusion. Our results indicated a high degree of heterozygosity, PIC and power of exclusion for Apo B3 HVR. These criteria lead us to investigate this marker for different purposes like detection of maternal contamination in chorionic villus samples and chimerism studies after the engraftment of bone marrow in bone marrow transplantation patients. The utility of this marker has been discussed in comparison of other markers.
Indian populations possess an exclusive genetic profile primarily due to the many migratory event... more Indian populations possess an exclusive genetic profile primarily due to the many migratory events, which caused an extensive range of genetic diversity, and also due to stringent and austere sociocultural barriers that structure these populations into different endogamous groups. In the present study we attempt to explore the genetic relationships between various endogamous North Indian populations and to determine the effect of stringent social regulations on their gene pool. Twenty STR markers were genotyped in 1,800 random North Indians from 9 endogamous populations belonging to upper-caste and middle-caste Hindus and Muslims. All nine populations had high allelic diversity (176 alleles) and average observed heterozygosity (0.742 +/- 0.06), suggesting strong intrapopulation diversity. The average F(ST) value over all loci was as low as 0.0084. However, within-group F(ST) and genetic distance analysis showed that populations of the same group were genetically closer to each other. The genetic distance of Muslims from middle castes (F(ST) = 0.0090; DA = 0.0266) was significantly higher than that of Muslims from upper castes (F(ST) = 0.0050; DA = 0.0148). Phylogenetic trees (neighbor-joining and maximum-likelihood) show the basal cluster pattern of three clusters corresponding to Muslims, upper-caste, and middle-caste populations, with Muslims clustered with upper-caste populations. Based on the results, we conclude that the extensive gene flow through a series of migrations and invasions has created an enormous amount of genetic diversity. The interpopulation differences are minimal but have a definite pattern, in which populations of different socioreligious groups have more genetic similarity within the same group and are genetically more distant from populations of other groups. Finally, North Indian Muslims show a differential genetic relationship with upper- and middle-caste populations.
The allele frequency estimates of these STR markers reveal that alleles are not equally distribut... more The allele frequency estimates of these STR markers reveal that alleles are not equally distributed in all the three populations included in the study.
2014 USNC-URSI Radio Science Meeting (Joint with AP-S Symposium), 2014
Magnetic stimulation is an evolving, non-invasive neural stimulation technology used for clinical... more Magnetic stimulation is an evolving, non-invasive neural stimulation technology used for clinical applications, including brain mapping, treatment of mood disorders, epilepsy, and chronic pain. Based on the induction principle, magnetic stimulation induces electric fields in the conductive tissue due to the time-varying current in the magnetic coil. It requires the magnetic coil to be in close proximity to the stimulation site to produce neural activation. The stimulation threshold of magnetic stimulation depends on the magnitude and the pulse width of the induced electric field. Traditionally, the efficacy of the magnetic stimulation is studied using analytical formulations based on the coil parameters and operating conditions (Roth, B. J. et. al., IEEE TBME 1990). Several studies were performed to include the tissue boundaries in the simulation model of the induced electric field (Nagarajan, S.S. et al., IEEE TBME 1996). However, these models were over simplified and do not include the tissue heterogeneity found in the nerve bundle.
Short Tandem Repeat (STR) loci are widely considered to be effective for variety of applications ... more Short Tandem Repeat (STR) loci are widely considered to be effective for variety of applications including forensic applications, phylogenetic reconstruction and chimerism based post Haematopoietic Stem Cell Transplantation (HSCT) graft monitoring. For each application, specific sets of STR loci are used. In the present study, we have attempted to use same set of STR loci for varied purposes based on their efficacy and informativity. Population and patient based study. We have analyzed 5 STR loci--vWA, Tho1, FES, F13 and TPOX in 1000 North Indians. All five markers were also analyzed for chimerism based graft monitoring after HSCT in 42 HLA matched pair of patient-donor to predict the outcome of transplantation. The analysis was done for Hardy Weinberg equilibrium (HWE), Heterozygosity, Polymorphism information content (PIC) and Power of Exclusion and Phylogenetic assessment. High allelic variability in term of Heterozygosity (0.68-0.76), PIC (0.66-0.74) and high Power of exclusion ...
Forensic Short Tandem Repeat (STR) loci are effective for the purpose of individual identificatio... more Forensic Short Tandem Repeat (STR) loci are effective for the purpose of individual identification, and other forensic applications. Most of these markers have high allelic variability and mutation rate because of which they have limited use in the phylogenetic reconstruction. In the present study, we have carried out a meta-analysis to explore the possibility of using only five STR loci (TPOX, FES, vWA, F13A and Tho1) to carry out phylogenetic assessment based on the allele frequency profile of 20 world population and north Indian Hindus analyzed in the present study. Phylogenetic analysis based on two different approaches - genetic distance and maximum likelihood along with statistical bootstrapping procedure involving 1000 replicates was carried out. The ensuing tree topologies and PC plots were further compared with those obtained in earlier phylogenetic investigations. The compiled database of 21 populations got segregated and finely resolved into three basal clusters with very...
The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions... more The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1) is an important component of RAS which determines the vasoactive peptide Angiotensin-II. In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8) and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease d...
Human genome sequencing results revealed an insight into the role of human genetic variation behi... more Human genome sequencing results revealed an insight into the role of human genetic variation behind differential susceptibility of human diseases, differential response to pharmacological agents and presence of varied phenotypes. This leads to the concept of personalized medicine. In the present review we have discussed the objectives and approaches for carrying out pharmacogenomics and pharmacogenetics studies. The review also incorporates the major findings categorizing the common diseases on the basis of genetic profiles and ethnic information and in establishing personalized disease diagnosis, drug responses and treatment modalities based on the genetic determinants. Overall an attempt has been made to highlight the importance of studying the genetic profiles of an individual in biomedical and pharmacogenomics research.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2014
Efficacy of magnetic stimulation of the central or peripheral nervous system depends on the spati... more Efficacy of magnetic stimulation of the central or peripheral nervous system depends on the spatial and temporal distribution of the induced electric field generated by the magnetic coil. Therefore, accurate estimation of the induced electric field is crucial to the design and optimization of magnetic coils, particularly as the coil dimensions are reduced. In this work, we developed a numerical model of a multifascicular sciatic nerve to study the effect of tissue heterogeneity on the induced electric field. Using a multi-resolution electric field solver, we can resolve feature sizes as small as 1μm, allowing inclusion of the nerve membrane and the myelination layer. Preliminary results indicate that fascicle distribution and axons' proximity to each other significantly affect the magnitude and distribution of the induced electric field as compared to traditional homogeneous tissue models for field simulation.
Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells... more Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells against reactive oxygen species and plays a vital role in phase II of biotransformation of many substances. Overexpression of GST (EC 2.5.1.18) has been documented in the erythrocytes of patients with chronic renal failure, which may be of clinical relevance. Keeping this background in mind, we have investigated the relationship between human GST gene polymorphism in end stage renal disease (ESRD) patients. We have assessed 184 patients with ESRD and 569 age-and sex-matched controls from North India. The GSTT1 and GSTM1 null genotypes were identified by polymerase chain reaction (PCR). GSTP1-313 A/G mutation was determined by PCR followed by restriction enzyme digestion. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphism were evaluated. We observed that GSTM1 null genotype was present in 46.74% of the ESRD patients while GSTT1 null genotype was present in 58.7% of the ESRD subjects. The genotypic distribution of GSTP1 was Ile(105)/Ile(105) in 47.3%, Ile(105)/Val(105) in 30.97% and Val(105)/Val(105) in 21.74% of ESRD patients. There was a significant association of null alleles of the GSTM1 (p = 0.0386; OR = 1.445, 95% CI = 1.033-2.021) and GSTT1 (p < or = 0.0001; OR = 4.568, 95% CI = 3.215-6.492) and in the -313 G alleles (Val) of the GSTP1 gene (p = 0.0032; OR = 1.956, 95% CI = 1.265-3.024) with end stage renal disease. The combined analysis of the three genotypes showed a further increased risk to ESRD (p < or = 0.0001; OR = 9.01, 95% CI = 5.55-14.626). The null / low polymorphism of the detoxifying enzymes GSTT1, GSTM1, and GSTP1 are associated with the risk of developing ESRD in North Indian patients.
Renal allograft rejection or dysfunction often results in graft failure, and remains the major ob... more Renal allograft rejection or dysfunction often results in graft failure, and remains the major obstacle in the success of renal transplantation. Various immunological and nonimmunological factors are involved in allograft rejection. In addition to human leukocyte antigen loci, several genetically controlled molecules have been identified in recent years as playing important roles in the process of rejection. Genetic variants in genes encoding different T-helper (Th) type 1 and Th2 cytokines, chemokines and their receptors, growth factors, molecules of the renin-angiotensin system, enzymes of the homocysteine pathway, and proteins acting as substrates of immunosuppressive drugs impact on the success of engraftment and highlight the concept of genetic predisposition to allograft rejection. This review evaluates specific genetic variants and their functional roles in graft failure, with an emphasis on the latest methodologies available for genotyping, and appropriate strategies to enable them to become a tool of predictive and individualized medicine to ensure better transplant outcome.
Page 1. J Forensic Sci, July 2004, Vol. 49, No. 4 Paper ID JFS2004129 Published 26 May 2004 Avail... more Page 1. J Forensic Sci, July 2004, Vol. 49, No. 4 Paper ID JFS2004129 Published 26 May 2004 Available online at: www.astm.org FOR THE RECORD Faisal Khan,1 M.Sc.; Atul Kr. Pandey,1 M.Sc.; Manorama Tripathi,1 M.Sc ...
ApoB3&amp... more ApoB3' hyper variable region is one of the highly polymorphic genetic marker and reveals a high degree of allelic variation in different populations therefore; it can be a useful marker for different clinical tests in which individual differences at DNA level form the basis of detection. In the present study we compared Apo B3 HVR with other 28 STR markers at allele frequency level, heterozygosity, polymorphism information content (PIC) and power of exclusion. Our results indicated a high degree of heterozygosity, PIC and power of exclusion for Apo B3 HVR. These criteria lead us to investigate this marker for different purposes like detection of maternal contamination in chorionic villus samples and chimerism studies after the engraftment of bone marrow in bone marrow transplantation patients. The utility of this marker has been discussed in comparison of other markers.
Indian populations possess an exclusive genetic profile primarily due to the many migratory event... more Indian populations possess an exclusive genetic profile primarily due to the many migratory events, which caused an extensive range of genetic diversity, and also due to stringent and austere sociocultural barriers that structure these populations into different endogamous groups. In the present study we attempt to explore the genetic relationships between various endogamous North Indian populations and to determine the effect of stringent social regulations on their gene pool. Twenty STR markers were genotyped in 1,800 random North Indians from 9 endogamous populations belonging to upper-caste and middle-caste Hindus and Muslims. All nine populations had high allelic diversity (176 alleles) and average observed heterozygosity (0.742 +/- 0.06), suggesting strong intrapopulation diversity. The average F(ST) value over all loci was as low as 0.0084. However, within-group F(ST) and genetic distance analysis showed that populations of the same group were genetically closer to each other. The genetic distance of Muslims from middle castes (F(ST) = 0.0090; DA = 0.0266) was significantly higher than that of Muslims from upper castes (F(ST) = 0.0050; DA = 0.0148). Phylogenetic trees (neighbor-joining and maximum-likelihood) show the basal cluster pattern of three clusters corresponding to Muslims, upper-caste, and middle-caste populations, with Muslims clustered with upper-caste populations. Based on the results, we conclude that the extensive gene flow through a series of migrations and invasions has created an enormous amount of genetic diversity. The interpopulation differences are minimal but have a definite pattern, in which populations of different socioreligious groups have more genetic similarity within the same group and are genetically more distant from populations of other groups. Finally, North Indian Muslims show a differential genetic relationship with upper- and middle-caste populations.
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