Parvinder Kumar

Whole Exome Screening Identifies Novel and Recurrent WISP3 Mutations Causing Progressive Pseudorheumatoid Dysplasia in Jammu and Kashmir-India

We report identification and genetic characterization of a rare skeletal disorder that remained unidentified for decades in a village of Jammu and Kashmir, India. The population residing in this region is highly consanguineous and a lack of understanding of the disorder has hindered clinical management and genetic counseling for the many affected individuals in the region. We collected familial information and identified two large extended multiplex pedigrees displaying apparent autosomal recessive inheritance of an uncharacterized skeletal dysplasia. Whole exome sequencing (WES) in members of one pedigree revealed a rare mutation in WISP3:c.156Cu2009>u2009A (NP_003871.1:p.Cys52Ter), that perfectly segregated with the disease in the family. To our surprise, Sanger sequencing the WISP3 gene in the second family identified a distinct, novel splice site mutation c.643u2009+u20091Gu2009>u2009A, that perfectly segregated with the disease. Combining our next generation sequencing data with careful clinical documentation (familial histories, genetic data, clinical and radiological findings), we have diagnosed the families with Progressive Pseudorheumatoid Dysplasia (PPD). Our results underscore the utility of WES in arriving at definitive diagnoses for rare skeletal dysplasias. This genetic characterization will aid in genetic counseling and management, critically required to curb this rare disorder in the families.

Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene polymorphisms and associated risk of cardiovascular diseases: A study from Jammu region.

Aim Potent risk factors at both genetic and non-genetic levels are accountable for susceptibility and instigation of different cardiovascular phenotypes. Recently, homocysteine is being identified as an important predictor for cardiovascular diseases. Homocysteine remethylation plays a key role in the synthesis of methionine and S-adenosine methionine. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes are known to regulate the homocysteine remethylation reaction and higher homocysteine level is significantly associated with diverse cardiovascular phenotypes. In this context, we aimed to carry out a study on the association of MTHFR (C677T) and MTR (A2756G) gene polymorphism with CVD in population of Jammu region of J&K state. Materials and methods A total of 435 individuals were enrolled (195 CVD patients and 240 controls) for the case–control study. Genotyping of MTHFR C677T and MTR A2756G gene polymorphism was done by PCR-RFLP technique. Biochemical parameters were estimated by biochemical analyser. Results Metabolic variables such as serum LDL-C, TC and TG were significantly higher in patients (p < 0.0001), whereas serum HDL-C was higher in controls. Majority of the patients were having history of hypertension (57.44%; p < 0.0001) as a concomitant condition. The evaluation of genetic association showed that, MTHFR C6877T (OR: 8.89, 95% CI: 2.01–39.40) and MTR A2756G (OR: 1.48, 95% CI: 1.09–2.00) polymorphisms associated with higher risk of CVD. Conclusion The present study reveals significant differences in nongenetic variables among patients and control as well as association of gene polymorphisms with CVD risk.

Comprehensive SNP Analysis of Genes in Cholestrol Metabolism (PGC 1 Alpha), Insulin Signaling (IRS1), Potassium Channel (KCNJ11) and Glucose Homeostasis (PI3K) in Three Diversified Groups

Objective: Type 2 Diabetes is an increasingly common serious, metabolic disorder with a substantial inherited component. We examined 4 SNPs in 4 candidate genes for association with diabetes status and related phenotype in 800 individuals in a case control study. nResearch design and methodology: We examined SNPs of 4 candidate genes predicted to have their major role in T2DM. A total of 800 subjects were enrolled (400 patients and 400 controls) from North Indian Population of Jammu and Kashmir from three ethnic groups (Brahmins 200, Khatris 100, Guptas 100). Genotypic analysis was followed by DNA extraction and PCR RFLP technique. nResults: The results confirmed the genetic complexity of Type 2 Diabetes and provide evidence that PGC 1 Alpha (Gly482Ser) and PI3K (Met 326 Ile) polymorphisms have altered the cholesterol pathway and glucose homeostasis and signified the risk of T2DM.

Androgen Insensitivity Syndrome (Testicular Feminization)

Androgen insensitivity (testicular feminization) syndrome is a rare inherited form of male pseudohermaphroditism that occurs in phenotypically normal women with adequate breast development, normal external genitalia, a vagina of variable depth, absent uterus, and sparse or absent pubic hair and axillary hair. These patients have male karyotype (XY) and negative sex chromatin. The gonad (undescended testis) may be intraabdominal, inguinal, or labial [1]. The incidence of testicular feminization syndrome is reported to range between one in 2,000 to one in 62,400 [2]. The present case is the first one from Jammu and Kashmir State of India where chromosome study has been carried out and 46, XY karyotype has been detected in the phenotypic female.

An Efficient Risk Analysis based Risk Priority in Requirement Engineering using Modified Goal Risk Model

Risk analysis is traditionally considered a critical activity for the whole software system‟s lifecycle. Risks are identified by considering technical aspects (e.g., failures of the system, unavailability of services, etc.) and handled by suitable countermeasures through a refined design. A modified Tropos goal model was developed in which the evidence of satisfaction and denial of the goal is calculated from the likelihood of the events corresponding to the goals. Relations are defined between multiple goals and events, which define the importance of a particular goal. The event may be considered as a risk according to their likelihood value. So the inter relation values of the goals and events gives the impact of that event on the particular goal. In order to analyze the risk in achieving some particular goals, a set of candidate solutions are generated. The candidate solutions are evaluated on the basis of a risk affinitive value of the goals according to their events. The risk affinitive value is calculated from the different set of risk parameters, which is set like high, medium and low. The risk parameters clearly evaluate the affinity of that event to a particular set of goals. A priority based parameter is added to the proposed approach to sort out the risk values. According to the proposed approach distinct cost to risk values are achieved. Finally, the candidate solutions with low cost are selected.

Human- specific Alu Insertion/Deletion Polymorphisms in Various Population Groups of Jammu Region

Abstract In present study, six Alu insertion/deletion polymorphisms (Alu ACE, Alu APO, Alu PV-92, Alu PLAT, Alu FXIIIB and Alu D1) were studied in five different populations (Brahmins, Rajputs, Scheduled Castes, Gujjars and Jat Sikhs) of Jammu region. Blood samples were collected randomly from 400 unrelated healthy individuals. DNA was extracted and amplified by PCR using six target specific Oligonucleotide primers of Alu family and finally subjected to Agarose gel electrophoresis. Allele frequencies were used to calculate average heterozygosity. All the six markers were found to be highly polymorphic with high heterozygosity Values. The genetic distance analysis revealed a close genomic affinity between Schedule Castes and Jat Sikhs suggesting recent diversification of these two population groups whereas Gujjars and Brahmins stood apart genetically.

Study of Risk Factors for the High Prevalence of Type 2 Diabetes in the People of Jammu

Abstract The study was carried out to identify the contribution of risk factors to the susceptibility to T2DM among the people of Jammu region of Jammu and Kashmir state in North India. For this, a total of 250 diabetic patients (140 male, 110 female) and 150 non-diabetic controls (90 male, 60 female) were recruited from Jammu. A general health questionnaire was used to collect information about age, sex, onset of diabetes, smoking, alcohol intake, diet pattern, physical activity, household information and family history of diabetes. Anthropometric measurements of height, weight, waist and hip circumference were also taken on all subjects. In our study mean age of diagnosis of T2DM was 53.28±9.98 years. The average duration of diabetes was longer in males than in females (10.16±11.37yr) vs. (7.17± 5.05yr). The mean BMI value did not vary among diabetic and non-diabetic subjects (25.91±3.82 vs. 24.91± 3.65; P = .011) but male diabetics have higher BMI as compared to females. Diabetic complications are higher in T2DM subjects than in Control population (28 percent CHD, 32 percent Hypertension, 40 percent Ocular Problem). It is concluded that the Jammu population in North India is at a higher risk of developing diabetes and its related complications.

Chromosomal Anomalies in Referred Cases with Suspected Genetic Disorders: First Report from Jammu and Kashmir

Abstract In a four year period (2005-2009), a total of 161 individuals of different age group presenting clinicalprofile like genetically uncertain syndrome, multiple congenital anomalies, short stature, facial dysmorphism, abnormalbehaviour, unclassified mental retardation and Down syndrome were referred to the Human Genetic Research cumCounselling centre, Jammu.Chromosome study was carried out in all the referred cases, when the chromosomalabnormalities were detected in 91 (56.52%) individuals. Besides chromosome study, some non-cytogenetic factorslike maternal age, male: female ratio, birth order and consanguinity have also been studied to find out the possibleassociation of these factors with chromosomal aberrations in referred patients.

Ancient Human Migrations to and through Jammu Kashmir- India were not of Males Exclusively

Jammu and Kashmir (J&K), the Northern most State of India, has been under-represented or altogether absent in most of the phylogenetic studies carried out in literature, despite its strategic location in the Himalayan region. Nonetheless, this region may have acted as a corridor to various migrations to and from mainland India, Eurasia or northeast Asia. The belief goes that most of the migrations post-late-Pleistocene were mainly male dominated, primarily associated with population invasions, where female migration may thus have been limited. To evaluate female-centered migration patterns in the region, we sequenced 83 complete mitochondrial genomes of unrelated individuals belonging to different ethnic groups from the state. We observed a high diversity in the studied maternal lineages, identifying 19 new maternal sub-haplogroups (HGs). High maternal diversity and our phylogenetic analyses suggest that the migrations post-Pleistocene were not strictly paternal, as described in the literature. These preliminary observations highlight the need to carry out an extensive study of the endogamous populations of the region to unravel many facts and find links in the peopling of India.

Clinical and cytogenetic analysis of human anemias from Jammu region of Jammu and Kashmir state.

Background: Anemias are the blood disorders characterized by reduction in the number of circulating red blood cells, the amount of hemoglobin, or the volume of packed red cells in blood. Chromosomal aberrations have often been reported from the bone marrow as well as cultured lymphocytes of the anemic patients. Aims: The aims of the study were to find out the commonest type of anemia occurring in the population of Jammu, India and to find out the chromosomal changes involved in the disorder. Material and Methods: Present study has been carried out on the bone marrow samples from 53 clinically diagnosed anemic patients. Cytogenetic study was carried out on slides prepared from these samples. Noncytogenetic factors like age, sex, religion, blood groups, family history of anemia, socioeconomic status, etc. have also been included in the study. Results: Megaloblastic anemia was found to be the commonest type of anemia. Centromere stretching, chromatid breaks, gaps, and elongation of chromosomes were recorded in patients with megaloblastic anemia and combined deficiency anemia. However, structural changes and numerical changes were totally absent. Conclusion: The commonest anemia among the people of Jammu region is megaloblastic anemia and its prevalence is increasing every year. Also, megaloblastic anemia is always associated with reversible cytogenetic changes.