Research Interests: Bioinformatics, Endocrinology, Genetics, Obesity, Biology, and 13 moreMedicine, Insulin Resistance, Internal Medicine, Hyperinsulinemia, Gene, Anovulation, Clinical Sciences, Genotype, Single Nucleotide Polymorphism, Public health systems and services research, Hyperandrogenism, Paediatrics and reproductive medicine, and Polycystic ovary
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e18576 Background: We prospectively studied 90 patients of multiple myeloma for the presence of translocations involving IgH (14q32) locus, del 13q14 and presence of numerical chromosomal abnormalities. An attempt was made to correlate... more
e18576 Background: We prospectively studied 90 patients of multiple myeloma for the presence of translocations involving IgH (14q32) locus, del 13q14 and presence of numerical chromosomal abnormalities. An attempt was made to correlate their effect on outcome and to formulate a risk scoring system. METHODS Purified bone marrow plasma cells, using magnetic activated cell sorter (MACS) with CD 138 micro beads were used. Fluorescent in situ Hybridization was used to detect IgH (14q32) translocations and del 13q14, while numerical chromosomal abnormalities were detected by conventional cytogenetics. RESULTS Patients' median age was 55 years (range, 34 to 75 years) and 67 were males (M: F: 2.9: 1). 24 patients had International staging system (ISS) stage I, stage II- 46 and 20 patients had stage III. On conventional cytogenetics metaphases were obtained in 53 (58%) patients; with numerical chromosomal abnormalities in 21 of 53 (40%), these included- hyperdiploid in 16 and hypodiploid-5. Remaining patients had normal metaphases. del 13q14 and t(14q32) were present in 51 (56%) and 75 (83%) patients, respectively. 65/90 (72%) patients received therapy with novel molecules and were evaluated using EBMT response criteria. Absence of del 13q14 was associated with higher response rate (23/26 vs 26/39, P <0.04) and better overall survival (79% vs 67%, p =0.07) and event free survival (70% vs 37%, p <0.03) at two years. Based on presence (1) or absence (0) of del 13q14 and ISS (I=0 vs II=0.5 vs III=1), a risk scoring model was obtained. 69% of the patients belonged to low risk category (risk score ≤1) and 31% were in high risk (risk score >1). Patients belonging to low risk had a higher response (91% vs 40%, p<.0001), better overall (77% vs 61%, p<.01) and event free (58% vs 32%, p<.01) survival at two years compared to patients with high risk. CONCLUSIONS del 13q14 and International staging system (ISS) are two important parameters and could be used to prognosticate patients at diagnosis.
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Background:Inflammatory responses within the peritoneal cavity may result in endometrial dysfunction in women with endometriosis. The true causes of this disease remain poorly understood. It is hypothesized that downstream toll-like... more
Background:Inflammatory responses within the peritoneal cavity may result in endometrial dysfunction in women with endometriosis. The true causes of this disease remain poorly understood. It is hypothesized that downstream toll-like receptors (TLRs) inflammatory cytokines in response to pathogens may be associated with endometriosis. So, this study was aimed at evaluating the expression of TLRs signaling and endometriosis-associated inflammatory responses.Methods:Totally, 20 infertile endometriosis patients and 20 normal women undergoing controlled ovarian stimulation were enrolled. The cellular pellet and supernatant were obtained by centrifugation of follicular fluid (FF). Evaluation of TLRs and their signaling pathway gene expression was performed on cellular pellets using quantitative-PCR. The supernatant was used for determination of cytokine protein expression by ELISA. The results are expressed as mean±SEM and a p<0.05 was considered statistically significant.Results:Quantitative-PCR analysis suggested that TLR1, 5, 6, 7, 8, 10, MYD88, NF-ĸB, IL-10 and TGF-β genes expression significantly increased in patients compared to the control group (p<0.05). TLR3, 9, INF-β genes expression was significantly lower in endometriosis than control group (p<0.05). There was no significant difference in the expression of TLR2, TLR4, TIRAP, TRIF, TRAM, and IRF3 between two groups. Also, significant increase in the levels of IL-6, IL-8 and MIF protein in FF of endometriosis group was detected in comparison with normal women (p<0.05).Conclusion:The expression of TLR downstream signaling in the follicular cells can initiate inflammatory responses and changes in the FF cytokine profile which in turn may induce endometriosis and infertility disorder.
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: Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine implicated in various physiological and pathological events. Carnitine is a quaternary amine which plays a significant role in fatty acid oxidation and is reported to... more
: Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine implicated in various physiological and pathological events. Carnitine is a quaternary amine which plays a significant role in fatty acid oxidation and is reported to produce antiapoptotic effects. Aim of this work was to study the effect of L-Carnitine (LC) on TNF-α induced apoptosis in mice oocytes. : Oocytes were isolated from super ovulated Swiss Albino mice and treated with different concentrations of TNF-α (0.1ng/ml, 1ng/ml, 10ng/ml, 100ng/ml) and LC (0.1mg/ml, 0.3mg/ml, 0.5mg/ml, 1.0 mg/ml). TUNEL Assay was done for the biochemical assessment of apoptosis.: Apoptotic indices with different doses of TNF-α (0.1ng/ml, 1ng/ml, 10ng/ml, 100 ng/ml) were 28.5%, 71.4%, 100%, 42.8% respectively. The concentration of TNF-α that produced the highest apoptotic index was 10ng/ml. LC alone in different doses (0.1mg/ml, 0.3mg/ml, 0.5mg/ml, 1.0 mg/ml) did not elicit any apoptotic signal. Further LC was added in different doses with 10ng/ml TNF-α to study the rate of apoptosis in mice oocytes. Apoptotic index with 10 ng/ml TNF-α and different doses of LC (0.1mg/ml, 0.3mg/ml, 0.5mg/ml, 1 mg/ml) were 25%, 37.5%, 50%, 62.5% respectively. The concentration of LC that reduced the apoptotic index to the maximum was 0.1mg/ml.: Present study could demonstrate the anti-apoptotic effect of LC against apoptotic effects of TNF-α in mice oocytes. The study presents preliminary data suggesting a possible therapeutic role of LC in inflammatory etiologies such as ovarian failure.
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We report the seventh family of Fowler like syndrome (proliferative vasculopathy and hydrocephaly-hydrencephaly syndrome) and first case from Indian subcontinent. A 35 weeks extremely growth retarded male baby showed enlarged ventricles,... more
We report the seventh family of Fowler like syndrome (proliferative vasculopathy and hydrocephaly-hydrencephaly syndrome) and first case from Indian subcontinent. A 35 weeks extremely growth retarded male baby showed enlarged ventricles, thinned out cerebral cortex, diffuse intra-cerebral as well as peri-ventricular calcification, cerebral and corneal vasculopathy, unilateral micro-ophthalmia along with corneal opacity and depressed pulsatile anterior fontanel. This case was different from others concerning association with extreme oligohydramnios (in contrast to polyhydramnios), extreme growth restriction (in contrast to normal growth) and absence of gross muscle hypoplasia. No causative factors like TORCH infection, chromosomal abnormality or positive family history was noted in this case.
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Meiotic segregation of chromosomes X,Y and 1 was analyzed by triple colour rapid fluorescent in situ hybridization (FISH) with directly labelled probes on 4506 non-decondensed and non-cleaned interphase spermatozoa from four healthy male... more
Meiotic segregation of chromosomes X,Y and 1 was analyzed by triple colour rapid fluorescent in situ hybridization (FISH) with directly labelled probes on 4506 non-decondensed and non-cleaned interphase spermatozoa from four healthy male donors to test the possibility of rapid sperm FISH by omitting the conventional sperm decondensation and cleaning steps. Only 0.15 per cent of sperms were without any signals which suggested high hybridization success. An abnormal number of signals was seen in 1.6 per cent of sperms. Chromosome specific as well as donor specific segregation error was seen similar to previous reports. There was a wide variation in the ratio of normal X and Y bearing sperm from donor to donor. This study indicated that for segregation studies sperm FISH can be carried out in three hours with directly labelled probes without the steps for separation of sperm from somatic cells (cleaning), sperm swelling and sperm DNA decondensation.
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Prader Willi syndrome (PWS) most commonly is due to paternal micro-deletion of 15q11-q13. Although PWS is not a rare condition, mosaic micro-deletion cases are reported rarely. FISH using PWS micro-deletion probe is the most useful method... more
Prader Willi syndrome (PWS) most commonly is due to paternal micro-deletion of 15q11-q13. Although PWS is not a rare condition, mosaic micro-deletion cases are reported rarely. FISH using PWS micro-deletion probe is the most useful method to detect deletion including mosaicism. In this report we describe a female child with clinical features of atypical PWS and FISH analysis showing mosaicism for deletion in the PWS critical region. This is first mosaic deletion case of PWS from Indian subcontinent.
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We have evaluated the suitability of different formalin fixed paraffin embedded tissues i.e., brain, bone, liver and placenta, for fluorescence in situ hybridization (FISH) efficiency and chromosomal ploidy detection employing directly... more
We have evaluated the suitability of different formalin fixed paraffin embedded tissues i.e., brain, bone, liver and placenta, for fluorescence in situ hybridization (FISH) efficiency and chromosomal ploidy detection employing directly labelled repetitive sequence probes for chromosome X, Y and 1. The study was carried out on four foetal autopsy specimens. Cells from 50 mu thick tissue sections were dissociated before performing mono and multicolour FISH with directly labelled probes. Hybridization efficiency was maximum with brain tissue (81, 55 and 24% for mono, dual and triple colour FISH, respectively), followed by bone (45 and 34% for mono and dual colour FISH), liver (38, 19 and 0% for mono, dual and triple colour FISH) and placenta (14, 5 and 0% for mono, dual and triple colour FISH). These results indicated that brain is the most efficient material followed by bone, liver placenta for chromosome ploidy detection by FISH in formalin fixed tissues.
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ABSTRACT Disorder of sex development is defined as developmental abnormality in which determination and/or differentiation of chromosomal, gonadal or phenotypic sex is abnormal. This is a common disorder and a precise diagnosis is very... more
ABSTRACT Disorder of sex development is defined as developmental abnormality in which determination and/or differentiation of chromosomal, gonadal or phenotypic sex is abnormal. This is a common disorder and a precise diagnosis is very important for right management to prevent future psychosexual problems. The aim of this study was to evaluate the clinical features documented, investigative procedures followed and corrective interventions adopted during the course of the study and recommend how these cases could be managed satisfactorily without high end investigative support. This study describes the spectrum of cases of disorder of sex development in a referral tertiary care hospital in North India. The medical records of 63 patients presenting with disorder of sex development over a period of three years were reviewed. On the basis of meticulous clinical evaluation and minimal investigations (chromosomal, hormonal, biochemical, radiological, genitoscopy and laparoscopy/laparotomy/ gonadal biopsy) cases were categorized as 46,XY disorder of sex development (40 cases/63.5%), 46,XX disorder of sex development (14 cases/22.2%) and gonadal differentiation disorder of sex development (ovotesticular disorder of sex development &amp; gonadal dysgenesis; 9 cases/14.3%). Ambiguous genitalia/precocious puberty was the main presentation in 46,XX disorder of sex development whereas ambiguous genitalia/under development of breast or breast development at puberty was the main presentation in 46,XY disorder of sex development. Ambiguous genitalia was the major presenting complaint of cases of gonadal differentiation disorder of sex development. There were three peaks of age at presentation; infancy, childhood and postpubertal period. Mullerian ducts remnants were found in nine (22.5%) of 46,XY disorder of sex development. Male like external genitalia with bilateral cryptorchidism were also evident with 46,XX disorder of sex development. Sex assignment/reassignment was based mainly on virilization of external genitalia (phallus size) and testosterone response (excepting 46,XX disorder of sex development). The study concludes that with meticulous clinical evaluation and base line investigations cases of disorder of sex development can be managed well
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The majority of second‐trimester partial moles are found in association with triploidy. Rarely are they associated with tetraploidy or other aneuploidies and, to our knowledge, this is the first reported case of the prenatal diagnosis of... more
The majority of second‐trimester partial moles are found in association with triploidy. Rarely are they associated with tetraploidy or other aneuploidies and, to our knowledge, this is the first reported case of the prenatal diagnosis of partial mole in a pregnancy presenting with trisomy. The patient was referred at 21 weeks of gestation after a routine ultrasound examination had shown fetal and placental features suggesting a partial mole triploidy. Owing to the severe structural malformations and poor prognosis, the parents requested termination. Prenatal and postnatal cytogenetic investigations demonstrated an additional chromosome 13. Histopathological examination of the placenta showed focal areas of villous edema but no evidence of trophoblastic dysplasia. The maternal serum human chorionic gonadotropin level was within the normal range at all times. This case shows that trisomy can resemble a triploid partial mole in utero without the potential long‐term risk to the mother of persisting trophoblastic disease, as villous molar changes can obviously develop without trophoblastic dysplasia. Copyright © 1998 International Society of Ultrasound in Obstetrics and Gynecology
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Increasing HER-2/neu resistance in gastric carcinoma has encouraged search for new biomarkers for targeted therapy. Cellular mesenchymal epithelial transition (C-MET) is one such tyrosine kinase inhibitor proposed for personalized salvage... more
Increasing HER-2/neu resistance in gastric carcinoma has encouraged search for new biomarkers for targeted therapy. Cellular mesenchymal epithelial transition (C-MET) is one such tyrosine kinase inhibitor proposed for personalized salvage treatment. We determined frequency of C-MET gene copy number variation (CNV) by Fluorescent in-situ hybridization (FISH) in gastric adenocarcinoma (GAC) and sought its correlation with conventional clinicopathologic parameters. Dual-coloured FISH was done on 32 GAC cases. C-MET gene and centromere 7 signals were counted under fluorescent microscope and ratio was calculated for each case. Correlation between C-MET CNV and conventional clinic-pathologic parameters was done by Fischer exact test. CNV was identified in the form of amplification and polysomy (3.1% each) and associated with poorer prognostic parameters. Our pilot study highlights limited subset of patients that may benefit from anti-C-MET-targeted therapy and thus could be a novel biomarker for targeted intervention in GAC.
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Primary testicular failure and its subtypes Etiology Biomarkers Principles of diagnostic evaluation and management
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Sertoli cell only syndrome (SCOS) is characterized by complete absence of germ cells in seminiferous tubules of testis. SCOS is multifactorial but genetic factor play a major role in pathogenesis of the disorder with idiopathic origin.... more
Sertoli cell only syndrome (SCOS) is characterized by complete absence of germ cells in seminiferous tubules of testis. SCOS is multifactorial but genetic factor play a major role in pathogenesis of the disorder with idiopathic origin. Genetic factor majorly includes sex chromosomal aneuploidy and Yq Microdeletion. But a large number of cases are still idiopathic. The study aimed to evaluate the genomic imbalances (CNVs and LOH) in idiopathic SCOS patients. The study is based on 28 apparent idiopathic SCOS cases and 10 controls. Molecular cytogenetic techniques viz., FISH, STS-Multiplex PCR and Affymetrix cytoscan microarray (750K) were used. The microarray screened whole genomic imbalances in DNA from peripheral blood for 25 cases (excluded Klinefelter syndrome patients) and testicular FNAC sample for 2 cases. High FSH and low Inhibin B were observed in cases than controls groups. Four cases of sex chromosomal abnormality (i.e., three non-mosaic 47,XXY males and one non-mosaic 46,XX male) as well as four cases of Yq microdeletion (i.e., three cases with AZFc deletion and one case with complete AZFa, b and c deletion) were identified. Microarray detected unbalanced translocation of two segments of Y-chromosome i.e., Yp11.31-p11.2 (∼4.o mb region, involving SRY) and Yp11.2 (∼2.5 mb region) on X-chromosome in XX male. Also, loss of segment on same X-chromosome involving PAR1 region was identified. We have identified both autosomal and sex chromosomal CNVs (recurrent as well as private) involving candidate genes like SYCE1, ZFPM2, SRPK1, DAZ1, BPY2, HSFY1, VCY1 etc. All these CNVs possibly associated with SCOS pathogenesis. CNVs identified in cases that were already reported as pathogenic variant in clinical database DECIPHER. Microarray also detected many LOH (all autosomal, >3.0 mb size) that covered genes with spermatogenesis related function. The mechanism of action of LOH in pathogenesis of SCOS is still unravelled. CNVs and LOH related to spermatogenesis identified from two different sample types (blood vs. testicular tissue) were discordant. This study should be extended for larger cohort of patients.
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Structure of the Y chromosome Evolution of Y chromosome from autosomes Genes on human Y chromosome SRY gene and sex determination Azoospermia factors Copy number variations Functions Y chromosome-linked disorders
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Genetics and genomics play a role in the causation of various human diseases. A large number of human reproductive disorders also arise as a result of genetic and genomic abnormalities. Reproductive disorders associated with predominantly... more
Genetics and genomics play a role in the causation of various human diseases. A large number of human reproductive disorders also arise as a result of genetic and genomic abnormalities. Reproductive disorders associated with predominantly genetics and genomic abnormalities are infertility, early pregnancy loss, congenital malformations, difference or disorder of sex development and reproductive cancers. The genetic etiology of human reproductive disorders is increasing with improved molecular biology techniques such as DNA microarray and next-generation sequencing. Infertility is one of the significant areas of reproductive disorders where genetics/genomics plays a substantial role and may result from chromosomal, copy number variation, Yq &amp; pseudo autosomal region microdeletion/microduplication, gene mutation (monogenic, oligogenic, polygenic), multifactorial, epigenetic, mitochondrial, etc. abnormalities. All idiopathic infertile couples should be screened for genetic disorders before assisted reproduction to prevent transmission, if any, in offspring. Pregnancy wastage in early pregnancy is very high (about 70%) and is mainly related to chromosome number, copy number variation, and some monogenic or epigenetic abnormalities. Therefore, all early pregnancy loss cases should also be tested for genetic causes. Congenital malformations are structural defects in embryo, fetus, or newborns and affect about 3% (major malformations) of all births. The malformations could be due to the abnormalities of chromosomes, copy number variation, monogenic, oligogenic, multifactorial, or environmental. Array CGH &amp;/or NGS should be used as the first step to screen congenital malformations. Differences/disorder of sex development is a developmental defect in which the determination and/or differentiation of chromosomal, gonadal, or phenotypic/anatomic sex is abnormal. It is a common disorder and is primarily related to genetic abnormalities. Therefore, a precise diagnosis, mainly through an array CGH and/or NGS, is crucial for the proper management to prevent future psychosexual problems and another birth with the disorder. Cancer is a genomic disorder characterized by genomic instability (due to a defect in DNA repair mechanism), uncontrolled replication (due to lack of response to inhibitory factors/loss of contact inhibition), neo-angiogenesis, invasion and metastasis. All cancer cases should be investigated for genomic markers (both hereditary and somatic) for precise diagnosis, prognosis, and genetic counseling. In this review, we will try to evaluate the role of genetics and genomics in the above-mentioned reproductive disorders, along with genetic &amp; genomic techniques used and reproductive counseling in addition to our experiences.
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Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy whose heterogeneous genetic basis results in a variable clinical presentation. One of the main clinical features of PCOS is hyperandrogenism which occurs due to... more
Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy
whose heterogeneous genetic basis results in a variable clinical presentation. One
of the main clinical features of PCOS is hyperandrogenism which occurs due to
dysregulation of ovarian and adrenal steroidogenesis. Aims: This study aimed
to investigate potentially pathogenic variants in steroidogenic genes associated
with PCOS. Settings and Design: This was a hospital‑based observational study.
Materials and Methods: We recruited 51 women who presented with PCOS.
Fasting blood samples were drawn from the participants and their whole‑exome
sequencing analysis was carried out to look for pathogenic variants involved in
steroidogenic pathways. The variants were predicted for their probable deleterious
effects on proteins through in silico prediction tools. We evaluated the variants
with respect to the hormonal characteristics and clinical outcomes of the
patients. Statistical Analysis Used: All variables were analysed using GraphPad
Prism 8. Kruskal–Wallis t‑test and Fisher’s exact test were used to compare
clinical parameters and frequency differences among PCOS patients with and
without variants. Results: The data presented here reveal eight heterozygous
exonic variants, namely CYP21A2 (p.Ala392Thr, p.Gln319Ter and p.I143N),
steroidogenic acute regulatory (p.Arg53 Leu), AKR1C3 (p.Phe205Val), P450
oxidoreductase (p.Val334Ile and p.Val251Met) and HSD17B6 (p.Gly40Ser), of
which three were pathogenic, and four variants of uncertain significance in 8 out
of 51 patients (15.68%). The identified variants were predicted to cause protein
destabilisation, thus likely contributing to the pathogenesis of PCOS. Some of the
variants showed significant differences between PCOS patients and population
database (P < 0.05). Conclusion: The results of this study add to the mutational
spectrum of steroidogenic genes and their association with PCOS.
whose heterogeneous genetic basis results in a variable clinical presentation. One
of the main clinical features of PCOS is hyperandrogenism which occurs due to
dysregulation of ovarian and adrenal steroidogenesis. Aims: This study aimed
to investigate potentially pathogenic variants in steroidogenic genes associated
with PCOS. Settings and Design: This was a hospital‑based observational study.
Materials and Methods: We recruited 51 women who presented with PCOS.
Fasting blood samples were drawn from the participants and their whole‑exome
sequencing analysis was carried out to look for pathogenic variants involved in
steroidogenic pathways. The variants were predicted for their probable deleterious
effects on proteins through in silico prediction tools. We evaluated the variants
with respect to the hormonal characteristics and clinical outcomes of the
patients. Statistical Analysis Used: All variables were analysed using GraphPad
Prism 8. Kruskal–Wallis t‑test and Fisher’s exact test were used to compare
clinical parameters and frequency differences among PCOS patients with and
without variants. Results: The data presented here reveal eight heterozygous
exonic variants, namely CYP21A2 (p.Ala392Thr, p.Gln319Ter and p.I143N),
steroidogenic acute regulatory (p.Arg53 Leu), AKR1C3 (p.Phe205Val), P450
oxidoreductase (p.Val334Ile and p.Val251Met) and HSD17B6 (p.Gly40Ser), of
which three were pathogenic, and four variants of uncertain significance in 8 out
of 51 patients (15.68%). The identified variants were predicted to cause protein
destabilisation, thus likely contributing to the pathogenesis of PCOS. Some of the
variants showed significant differences between PCOS patients and population
database (P < 0.05). Conclusion: The results of this study add to the mutational
spectrum of steroidogenic genes and their association with PCOS.
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Music in medicine is in use in various medical areas like neurological disorders, developmental abnormalities, psychiatric disorders, addictive disorders, terminal disorders, etc besides perioperative care. Music in perioperative care is... more
Music in medicine is in use in various medical areas like neurological disorders, developmental abnormalities, psychiatric disorders, addictive disorders, terminal disorders, etc besides perioperative care. Music in perioperative care is aimed at reducing anxiety, stress, and fear besides decreasing postoperative pain. The authors (first two) have experience in the use of pre-recorded music medicine in perioperative patient care. Preoperative music is mainly used to reduce patients’ anxiety, stress, and fear. The use of intraoperative music is controversial in surgical procedures under general anesthesia. Postoperative music, in general, is beneficial for pain management. This write-up provides an overview of published information on music in medicine, including historical and in particular perioperative care in anesthesia practice including use in cesarean section delivery. We searched PubMed and PubMed Central besides google search on “music in medicine” up to March 2022. There wa...
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Abstract 4987 Purpose: We prospectively studied patients of multiple myeloma (MM) for presence of t(14q32), and del13q14 on FISH and numerical chromosomal abnormalities on conventional cytogenetics(CC). Methods: Between February 2007 and... more
Abstract 4987 Purpose: We prospectively studied patients of multiple myeloma (MM) for presence of t(14q32), and del13q14 on FISH and numerical chromosomal abnormalities on conventional cytogenetics(CC). Methods: Between February 2007 and June 2009, 90 previously untreated patients of MM were enrolled,…
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Transcervical cell (TCC) samples were retrieved between 6 and 15 weeks of pregnancy by a simple and rapid method of aspiration. The presence of fetal cells was investigated by polymerase chain reaction (PCR) assays for the amplification... more
Transcervical cell (TCC) samples were retrieved between 6 and 15 weeks of pregnancy by a simple and rapid method of aspiration. The presence of fetal cells was investigated by polymerase chain reaction (PCR) assays for the amplification of DNA sequences from chromosomes X and Y, and of polymorphic short tandem repeats (STR) specific for chromosomes 21 and 18. As judged by the detection of Y-derived PCR products, fetal cells were present in 68% of TCC samples collected from mothers with male fetuses. Paternally inherited fetal STR markers were detected in 29.6% of the tested TCC samples, while a further 44% of samples were non-informative, as the fetus had inherited markers similar to those of the mother.
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Varying degrees of necrozoospermia are common findings in cases of male sub-fertility; however, it is rare to find persistent and 100 % necrozoospermia. A case of persistent 100 % necrozoospermia was presented in this paper, where... more
Varying degrees of necrozoospermia are common findings in cases of male sub-fertility; however, it is rare to find persistent and 100 % necrozoospermia. A case of persistent 100 % necrozoospermia was presented in this paper, where aneuploidy analysis was carried out on sperm. No known associations like thyrotoxicosis, genital infection, spinal injury and diabetes were found. Sperm fluorescent in situ hybridization (FISH) was carried out to evaluate sperm aneuploidy for chromosome 1, 9, 12, 13, 16, 18, 21, X and Y and did not show any excess of aneuploidy over controls. To the best of our knowledge, this is the first attempt on meiotic segregation analysis on 100 % necrozoospermic patients.
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Research Interests: Genetics, Pediatrics, Biology, Medicine, Cardiac Surgery, and 15 moreIndia, Congenital Heart Defects, Humans, Child, Fluorescence in situ hybridization, Female, Male, Research article, Infant, Karyotyping, Clinical Sciences, Prevalence, Fluorescent in situ hybridization, Child preschool, and Chromosome deletion
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Chromosome aneuploidy plays an important role in infertility, early pregnancy wastage and perinatal mortality. Cytogenetic... more
Chromosome aneuploidy plays an important role in infertility, early pregnancy wastage and perinatal mortality. Cytogenetic &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; fluorescent in situ hybridization (FISH) studies on developmentally arrested and morphologically poor embryo have shown high frequency of chromosomal abnormality and mosaicism. In this study, we attempted to evaluate chromosome aneuploidy and mosaicism on human embryos through the use of FISH. Sixty one grade IV un-transferable embryos were obtained from 25 patients undergoing in vitro fertilization (IVF). Forty six embryos were studied by FISH; 15 were lost during transport and handling. FISH probes (non-commercial) for centromeres of chromosome X, Y, 1 and 18 were used for the study. Zona of embryos were dissolved in 0.01N HCl containing 0.1 per cent Tween 20 for 2-3 min. Interpretable FISH results were obtained in 24 embryos. Nineteen embryos (79.2%) were disomic (normal) for chromosome X/Y or 1/18 and five (20.8%) were abnormal. Among five abnormal embryos two were triploidy (from same patient), one was double mosaic aneuploidy, one was mosaic aneuploidy and one was trisomy for sex chromosome (XXY). There was eleven embryos with presence of Y chromosome i.e., male and three embryos were female. Skewing of sex ratio (11M vs. 3F) and low chromosome aneuploidy were observed in this preliminary study, however, it will be premature to conclude as the numbers of embryos studied were limited and so were the numbers of FISH probes used.
Research Interests: Andrology, Biology, Medicine, Embryo, Pregnancy, and 13 moreHumans, Fluorescence in situ hybridization, Female, Male, Aneuploidy, Preimplantation genetic diagnosis, Trisomy 21, Chromosome, Fertilization in Vitro, Mosaicism, Pilot Projects, Medical and Health Sciences, and Tissue and organ procurement
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Research Interests: Pathology, Cognitive Science, Immunohistochemistry, Adolescent, Comparative Study, and 15 moreMedicine, In Situ Hybridization, Humans, Fluorescence in situ hybridization, Female, Male, Astrocyte, Clinical Sciences, Middle Aged, Adult, Glial Fibrillary Acidic Protein, Astrocytoma, Neurosciences, Brain Neoplasms, and Oligodendroglioma
ObjectiveCervical cancer screening by primary human papilloma virus detection and cytology is fraught with low specificity and variable sensitivity, respectively. Cytology‐histology correlation remains modest. Biomarkers associated with... more
ObjectiveCervical cancer screening by primary human papilloma virus detection and cytology is fraught with low specificity and variable sensitivity, respectively. Cytology‐histology correlation remains modest. Biomarkers associated with early genetic events in cervical squamous carcinogenesis and detectable in cytology material are likely to be relevant. Human telomerase RNA component (hTERC) gene overexpression and aneuploidy are promising candidates in view of their reported early and consistent association with cervical squamous oncogenesis.MethodsWe analysed hTERC gene expression and chromosome 7 ploidy by fluorescent in‐situ hybridisation (FISH) in 50 women with cytological precursor squamous intraepithelial lesions and available histology outcomes. Results were expressed as percentages of cells showing ≥3 signals, mean signals/nucleus, and maximum amplitude across various cytology and histology categories. Proportions of positive cases were calculated from threshold values der...
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Skewing of the sex ratio towards males occurs in humans. The possible explanation for excess male births could be a preference for Y-bearing sperm at fertilization and/or selective elimination of female embryos during pregnancy. In this... more
Skewing of the sex ratio towards males occurs in humans. The possible explanation for excess male births could be a preference for Y-bearing sperm at fertilization and/or selective elimination of female embryos during pregnancy. In this study, we have tested the sex ratio in the preimplantation embryo (2-3 cells stage/closest possible primary sex ratio), the post-implantation embryo (day E7.5), and at birth (secondary sex ratio) on a homogenous (genetic, environmental, and dietary) population of mice to ascertain the biological reason i.e., male preference at fertilization or female elimination during pregnancy or both. Primary sex ratio on early preimplantation embryos (2-3 cells stage) was studied on 598 embryos and secondary sex ratio (at birth) on 721 pups using PCR-based sexing (both X & Y chromosome-specific) besides sex ratio of 80 post-implantation embryos (day E7.5). We have also investigated whether the fat content (high & low) of the diet affects the sex ratio. We observed a skewed sex ratio (more female) in preimplantation embryos (0.436; 95 % CI 0.39, 0.48), and post-implantation embryos (0.462; 95 % CI 0.35, 0.57) but reverse skewing (more male) at birth (0.539; 95 % CI 0.5, 0.58). We also observed that high-fat diet promoted male sex ratio at birth (0.657; 95 % CI 0.57, 0.74) whereas a low-fat diet had the opposite effect (0.46; 95 % CI 0.36, 0.56) but no effect at fertilization (2-3 cells stage embryos). This indicates selective elimination of female embryo and fetus throughout pregnancy in mice, more so with a high-fat diet.
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Oxysterols play vital roles in the human body, ranging from cell cycle regulation and progression to dopaminergic neurogenesis. While naïve human mesenchymal stem cells (hMSCs) have been explored to have neurogenic effect, there is still... more
Oxysterols play vital roles in the human body, ranging from cell cycle regulation and progression to dopaminergic neurogenesis. While naïve human mesenchymal stem cells (hMSCs) have been explored to have neurogenic effect, there is still a grey area to explore their regenerative potential after in vitro differentiation. Hence, in the current study, we have investigated the neurogenic effect of 22(R)-hydroxycholesterol (22-HC) on hMSCs obtained from bone marrow, adipose tissue and dental pulp. Morphological and morphometric analysis revealed physical differentiation of stem cells into neuronal cells. Detailed characterization of differentiated cells affirmed generation of neuronal cells in culture. The percentage of generation of non-DA cells in the culture confirmed selective neurogenic potential of 22-HC. We substantiated the efficacy of these cells in neuro-regeneration by transplanting them into Parkinson’s disease Wistar rat model. MSCs from dental pulp had maximal regenerative ...
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Structure of gonadotropin-releasing hormone (GnRH) Structure of GnRH receptor Synthesis and regulation of GnRH receptor GnRH-GnRH receptor interactions GnRH pulses Regulation of GnRH secretion Structure of gonadotropins Regulation of... more
Structure of gonadotropin-releasing hormone (GnRH) Structure of GnRH receptor Synthesis and regulation of GnRH receptor GnRH-GnRH receptor interactions GnRH pulses Regulation of GnRH secretion Structure of gonadotropins Regulation of gonadotropin secretion
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Primary testicular failure and its subtypes Etiology Biomarkers Principles of diagnostic evaluation and management
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Sertoli cell only syndrome (SCOS) is characterized by complete absence of germ cells in seminiferous tubules of testis. SCOS is multifactorial but genetic factor play a major role in pathogenesis of the disorder with idiopathic origin.... more
Sertoli cell only syndrome (SCOS) is characterized by complete absence of germ cells in seminiferous tubules of testis. SCOS is multifactorial but genetic factor play a major role in pathogenesis of the disorder with idiopathic origin. Genetic factor majorly includes sex chromosomal aneuploidy and Yq Microdeletion. But a large number of cases are still idiopathic. The study aimed to evaluate the genomic imbalances (CNVs and LOH) in idiopathic SCOS patients. The study is based on 28 apparent idiopathic SCOS cases and 10 controls. Molecular cytogenetic techniques viz., FISH, STS-Multiplex PCR and Affymetrix cytoscan microarray (750K) were used. The microarray screened whole genomic imbalances in DNA from peripheral blood for 25 cases (excluded Klinefelter syndrome patients) and testicular FNAC sample for 2 cases. High FSH and low Inhibin B were observed in cases than controls groups. Four cases of sex chromosomal abnormality (i.e., three non-mosaic 47,XXY males and one non-mosaic 46,XX male) as well as four cases of Yq microdeletion (i.e., three cases with AZFc deletion and one case with complete AZFa, b and c deletion) were identified. Microarray detected unbalanced translocation of two segments of Y-chromosome i.e., Yp11.31-p11.2 (∼4.o mb region, involving SRY) and Yp11.2 (∼2.5 mb region) on X-chromosome in XX male. Also, loss of segment on same X-chromosome involving PAR1 region was identified. We have identified both autosomal and sex chromosomal CNVs (recurrent as well as private) involving candidate genes like SYCE1, ZFPM2, SRPK1, DAZ1, BPY2, HSFY1, VCY1 etc. All these CNVs possibly associated with SCOS pathogenesis. CNVs identified in cases that were already reported as pathogenic variant in clinical database DECIPHER. Microarray also detected many LOH (all autosomal, >3.0 mb size) that covered genes with spermatogenesis related function. The mechanism of action of LOH in pathogenesis of SCOS is still unravelled. CNVs and LOH related to spermatogenesis identified from two different sample types (blood vs. testicular tissue) were discordant. This study should be extended for larger cohort of patients.
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Introduction: Polycystic Ovary Syndrome (PCOS) is a complex reproductive disorder characterised by hyperandrogenism, ovulatory dysfunction and polycystic/enlarged ovary. Although clinical and/or biochemical hyperandrogenism is one of the... more
Introduction: Polycystic Ovary Syndrome (PCOS) is a complex reproductive disorder characterised by hyperandrogenism, ovulatory dysfunction and polycystic/enlarged ovary. Although clinical and/or biochemical hyperandrogenism is one of the major features of PCOS, biochemical hyperandrogenism in the form of high testosterone and/or Free Androgen Index (FAI) is rarely observed in the Asian Indians. Aim: To assess various androgens to determine best available biomarker of androgens in PCOS from North India. Materials and Methods: This case-control study was conducted at Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India, between January 2016 to December 2019. During this period 137 female with PCOS and 49 female as control were included. Serum total testosterone (T), FAI, Dehydroepiandrosterone Sulphate (DHEAS), androstenedione and Dihydrotestosterone (DHT) were measured besides assessment of hirsutism using the FerrimanGallwey (FG) scale. Stati...
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BACKGROUND: It is known that 22q11.2 microdeletion is a submicroscopic chromosomal anomaly with cardiac and extra-cardiac manifestations. The prevalence and manifestations in north India have not been well characterized. OBJECTIVES: This... more
BACKGROUND: It is known that 22q11.2 microdeletion is a submicroscopic chromosomal anomaly with cardiac and extra-cardiac manifestations. The prevalence and manifestations in north India have not been well characterized. OBJECTIVES: This study was designed to determine the prevalence of 22q11.2 microdeletion in congenital cardiac malformation cases referred for surgery from north India and to assess ability of clinical criteria to predict the presence or absence of 22q11.2 microdeletion. METHODS: A total of 121 cardiac malformation cases requiring surgery (conotruncal as well as non conotruncal heart defect) were prospectively screened for 22q11.2 microdeletion using fluorescence in situ hybridization test. Detailed clinical information was obtained from all cases. RESULTS: Four out of 121 patients (prevalence 3.3%) had 22q11.2 microdeletion (all with tetralogy of Fallot). In all of these four patients, typical dysmorphic features of 22q11.2 microdeletion were present. None of the c...
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Macroprolactinemia is characterized by predominance of macroprolactin molecules in circulation and generally has extra-pituitary origin. Macroprolactin is viewed as biologically inactive, therefore asymptomatic, and thus may not require... more
Macroprolactinemia is characterized by predominance of macroprolactin molecules in circulation and generally has extra-pituitary origin. Macroprolactin is viewed as biologically inactive, therefore asymptomatic, and thus may not require any treatment or prolonged follow-up. In addition, data on prevalence of macroprolactinemia and its clinical manifestation are also rare. Therefore, the present study was aimed to find out prevalence of macroprolactinemia and its association, if any, with reproductive manifestations. Macroprolactin was measured in 102 hyperprolactinemia cases (>100 ng/ml prolactin level), 135 physiological hyperprolactinemia cases (50 pregnant and 85 lactating females; >100 ng/ml prolactin level) and 24 controls. Poly ethylene glycol (PEG) precipitation method was carried out to screen macroprolactin. Prolactin recovery of <25% was considered overt macroprolactinemia. Detailed clinical data was recorded which included complete medical history, physical exami...
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e18576 Background: We prospectively studied 90 patients of multiple myeloma for the presence of translocations involving IgH (14q32) locus, del 13q14 and presence of numerical chromosomal abnormalities. An attempt was made to correlate... more
e18576 Background: We prospectively studied 90 patients of multiple myeloma for the presence of translocations involving IgH (14q32) locus, del 13q14 and presence of numerical chromosomal abnormalities. An attempt was made to correlate their effect on outcome and to formulate a risk scoring system. METHODS Purified bone marrow plasma cells, using magnetic activated cell sorter (MACS) with CD 138 micro beads were used. Fluorescent in situ Hybridization was used to detect IgH (14q32) translocations and del 13q14, while numerical chromosomal abnormalities were detected by conventional cytogenetics. RESULTS Patients' median age was 55 years (range, 34 to 75 years) and 67 were males (M: F: 2.9: 1). 24 patients had International staging system (ISS) stage I, stage II- 46 and 20 patients had stage III. On conventional cytogenetics metaphases were obtained in 53 (58%) patients; with numerical chromosomal abnormalities in 21 of 53 (40%), these included- hyperdiploid in 16 and hypodiploid-5. Remaining patients had normal metaphases. del 13q14 and t(14q32) were present in 51 (56%) and 75 (83%) patients, respectively. 65/90 (72%) patients received therapy with novel molecules and were evaluated using EBMT response criteria. Absence of del 13q14 was associated with higher response rate (23/26 vs 26/39, P <0.04) and better overall survival (79% vs 67%, p =0.07) and event free survival (70% vs 37%, p <0.03) at two years. Based on presence (1) or absence (0) of del 13q14 and ISS (I=0 vs II=0.5 vs III=1), a risk scoring model was obtained. 69% of the patients belonged to low risk category (risk score ≤1) and 31% were in high risk (risk score >1). Patients belonging to low risk had a higher response (91% vs 40%, p<.0001), better overall (77% vs 61%, p<.01) and event free (58% vs 32%, p<.01) survival at two years compared to patients with high risk. CONCLUSIONS del 13q14 and International staging system (ISS) are two important parameters and could be used to prognosticate patients at diagnosis.
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Introduction: Primary testicular failure (PTF) refers to conditions where testes fail to produce sperms despite adequate hormonal support. PTF is classified into four distinct subtypes viz., Sertoli Cell Only Syndrome (SCOS), Maturation... more
Introduction: Primary testicular failure (PTF) refers to conditions where testes fail to produce sperms despite adequate hormonal support. PTF is classified into four distinct subtypes viz., Sertoli Cell Only Syndrome (SCOS), Maturation Arrest (MA), Hypospermatogenesis (HS) and Tubular Fibrosis (TF). Despite efforts, causes of PTF in most cases are still unknown. This study is based on 140 apparent idiopathic PTF cases. Known causes viz., mumps orchitis, varicocele, torsion, trauma, cryptochidism, etc or treatment with chemotherapeutic drugs was excluded before inclusion into the study. Methods: Study groups were comprised of 54 cases of MA, 52 cases of SCOS and 34 cases of HS. FISH with XY probes were carried out in addition to conventional chromosome analysis to find out sex chromosome aneuploidy. STS PCR analysis was carried out for Yq microdeletion studies. There were 50 normal fertile male served as control. For sertoli cell maturity status anti−mullerian hormone and for sertol...
4987 Purpose: We prospectively studied patients of multiple myeloma (MM) for presence of t(14q32), and del13q14 on FISH and numerical chromosomal abnormalities on conventional cytogenetics(CC). Methods: Between February 2007 and June... more
4987 Purpose: We prospectively studied patients of multiple myeloma (MM) for presence of t(14q32), and del13q14 on FISH and numerical chromosomal abnormalities on conventional cytogenetics(CC). Methods: Between February 2007 and June 2009, 90 previously untreated patients of MM were enrolled,…
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BACKGROUND Cytokines play a crucial role in the growth, survival and dissemination of malignant plasma cells in patients of multiple myeloma (MM). We estimated concentrations of five key cytokines: Vascular Endothelial Growth Factor... more
BACKGROUND Cytokines play a crucial role in the growth, survival and dissemination of malignant plasma cells in patients of multiple myeloma (MM). We estimated concentrations of five key cytokines: Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Tumor Necrosis Factor- alpha (TNF- α), B-cell activating factor (BAFF), and Receptor Activator of Nuclear Factor-κB ligand (RANKL) in newly diagnosed and relapsed/refractory MM (RRMM). METHODS The study groups include 68 newly diagnosed and 21 relapsed/refractory (RR) MM patients. 32 out of 68 newly diagnosed MM patients were evaluated for serum cytokine concentrations after their treatment. For survival analysis, the various parameters were studied in relation to both progression free survival (PFS) and overall survival (OS). RESULTS The median serum levels of VEGF, IL-6, BAFF and RANKL were higher in RRMM compared with newly diagnosed patients. However, the difference was significant for BAFF levels (p = 0.04). The median serum levels of VEGF, IL-6, TNF-α, BAFF and RANKL were significantly higher in newly diagnosed and RRMM patients, compared to controls. We also observed lower plasma levels of VEGF (p=<0.0001) and BAFF (p=<0.0001) in BM compartment compared to the levels in serum from peripheral blood of newly diagnosed patients. Significant reduction in the median levels of IL-6, TNF-α, BAFF and RANKL was seen after 4-6 cycles of induction treatment in responders but not in non-responders. On survival analysis, RRMM patients had inferior median OS and PFS compared to that in newly diagnosed MM patients and found to be significantly associated with low haemoglobin representing the more aggressive disease biology in recurrent myeloma. The mean levels of IL-6 were significantly different in patients who died as compared to patients who were alive. CONCLUSIONS The present study demonstrates that the serum levels of VEGF, IL-6, TNF, BAFF and RANKL are significantly elevated and decrease significantly after treatment. The concentrations of circulating cytokines will reflect those of the bone marrow and could be used for subsequent analyses.
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Background: Sertoli cell only syndrome (SCOS) or germ cell aplasia is characterized by the existence of only sertoli cells in the seminiferous tubule without any germ cells. SCOS is a multifactorial disorder but genetic factors play a... more
Background: Sertoli cell only syndrome (SCOS) or germ cell aplasia is characterized by the existence of only sertoli cells in the seminiferous tubule without any germ cells. SCOS is a multifactorial disorder but genetic factors play a major role in pathogenesis of idiopathic SCOS. Case Presentation: Two cases of idiopathic SCOS had been reported with no non-genetic factor in their medical history that could play a role in aetiology of SCOS. Also, two normal fertile males were recruited as controls in this study. For evaluation of genomic imbalance, karyotyping (G-banding), FISH, STS-PCR and SNP microarray were carried out. SNP microarray was carried out in DNA of peripheral blood for cases as well as controls. However, for cases, SNP microarray was conducted in DNA of testicular Fine needle aspiration cytology (FNAC). Conclusion: No chromosome abnormality and Yq microdeletion was found in cases as well as in controls. Microarray detected many CNVs and LOH that cover genes with sperm...
8050Background: In multiple myeloma (MM), a variety of genetic events have been described to be associated with disease progression. Besides, the activation of the NF-κB (nuclear factor-kappa B) pa...
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ABSTRACT Cytogenetic abnormality is a major cause of genetic disease. It accounts for a large proportion of reproductive dysfunction (infertility), reproductive wastage (abortion), congenital malformations, mental retardation and cancer.... more
ABSTRACT Cytogenetic abnormality is a major cause of genetic disease. It accounts for a large proportion of reproductive dysfunction (infertility), reproductive wastage (abortion), congenital malformations, mental retardation and cancer. Advances in the field of cytogenetics have been to a large extent technology driven. After having reached the limits of optical resolution of chromosomes, the new wave is now moving from microscope to DNA sequences (molecular) for identification of chromosome alterations, including submicroscopic. This new molecular techniques are providing far more information at higher resolution on the human genome than just chromosome number &amp; morphology of conventional cytogenetics. Molecular technologies are increasingly being used to study cytogenetic abnormalities. Molecular cytogenetics are indicated to diagnose known chromosomal syndrome, microdeletion syndrome, psychomotor retardation, abnormalities of sexual differentiation/development, infertility, cancer, recurrent pregnancy loss and pregnancy at risk for aneuploidy. It is applied to study chromosomes in single cells like blastomere, polar body and gamete. Molecular cytogenetic approaches used widely are conventional Fluorescence in situ Hybridization (FISH), SKY/M FISH, fiber FISH, comparative genomic hybridization (CGH), Primed in situ Labeling/Synthesis (PRINS), quantitative fluorescent polymerase chain reaction/PCR (QF PCR), real time quantitative PCR (RT qPCR), array CGH/SNP microarray, next generation sequencing (NGS), etc. These techniques expanded the possibilities for precise genetic diagnosis, which are extremely important for clinical management of patients as well as research. This new wave is now on chromosome analysis from microscope to automated microarray/NGS for identification of chromosomal abnormality beyond cytogenetic resolution. The microarray based molecular karyotyping has become the primary choice to direct analysis of all chromosomes/genes in one action without subjective nature, without restriction to cytogenetic experts and difficult cell culture, for many indications. We are moving from cytogenetics to cytogenomics. It seems in near future aCGH &amp; NGS will replace conventional cytogenetics in most clinical &amp; research applications
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Copyright: © 2013 Halder A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author... more
Copyright: © 2013 Halder A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Chromosomal abnormalities are a major cause of genetic disease. It accounts for a large proportion of reproductive wastage, congenital malformations, mental retardation and most importantly, in the pathogenesis of cancer. Chromosomal study, also conventionally known as cytogenetics is indicated to diagnose known chromosomal syndrome, multiple malformations, unexplained psychomotor retardation (with or without dysmorphism), abnormalities of sexual differentiation and development, infertility, monogenic disorder associated with dysmorphism, cancer, recurrent pregnancy loss, pregnancy at risk for aneuploidy (prenatal/preimplantation/preconception) and in coming days for neuropsychiatric disorders, neurodegenerative disorders, microdeletion/microduplication syndromes and so on. Chromosomal study is also indicated for comparative mammalian cytogenetics, chromosome evolution, localization of disease gene, detection of chromosome breakage and mutagenicity study.
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The present study evaluated the role of SNP microarray in 101 cases of clinically suspected FISH negative (noninformative/normal) 22q11.2 microdeletion syndrome. SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or... more
The present study evaluated the role of SNP microarray in 101 cases of clinically suspected FISH negative (noninformative/normal) 22q11.2 microdeletion syndrome. SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or CytoScan 750 K array. SNP microarray identified 8 cases of 22q11.2 microdeletions and/or microduplications in addition to cases of chromosomal abnormalities and other pathogenic/likely pathogenic CNVs. Clinically suspected specific deletions (22q11.2) were detectable in approximately 8% of cases by SNP microarray, mostly from FISH noninformative cases. This study also identified several LOH/AOH loci with known and well-defined UPD (uniparental disomy) disorders. In conclusion, this study suggests more strict clinical criteria for FISH analysis. However, if clinical criteria are few or doubtful, in particular newborn/neonate in intensive care, SNP microarray should be the first screening test to be ordered. FISH is ideal test for detecting mosaicism...
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ABSTRACT Disorder of sex development is defined as developmental abnormality in which determination and/or differentiation of chromosomal, gonadal or phenotypic sex is abnormal. This is a common disorder and a precise diagnosis is very... more
ABSTRACT Disorder of sex development is defined as developmental abnormality in which determination and/or differentiation of chromosomal, gonadal or phenotypic sex is abnormal. This is a common disorder and a precise diagnosis is very important for right management to prevent future psychosexual problems. The aim of this study was to evaluate the clinical features documented, investigative procedures followed and corrective interventions adopted during the course of the study and recommend how these cases could be managed satisfactorily without high end investigative support. This study describes the spectrum of cases of disorder of sex development in a referral tertiary care hospital in North India. The medical records of 63 patients presenting with disorder of sex development over a period of three years were reviewed. On the basis of meticulous clinical evaluation and minimal investigations (chromosomal, hormonal, biochemical, radiological, genitoscopy and laparoscopy/laparotomy/ gonadal biopsy) cases were categorized as 46,XY disorder of sex development (40 cases/63.5%), 46,XX disorder of sex development (14 cases/22.2%) and gonadal differentiation disorder of sex development (ovotesticular disorder of sex development &amp; gonadal dysgenesis; 9 cases/14.3%). Ambiguous genitalia/precocious puberty was the main presentation in 46,XX disorder of sex development whereas ambiguous genitalia/under development of breast or breast development at puberty was the main presentation in 46,XY disorder of sex development. Ambiguous genitalia was the major presenting complaint of cases of gonadal differentiation disorder of sex development. There were three peaks of age at presentation; infancy, childhood and postpubertal period. Mullerian ducts remnants were found in nine (22.5%) of 46,XY disorder of sex development. Male like external genitalia with bilateral cryptorchidism were also evident with 46,XX disorder of sex development. Sex assignment/reassignment was based mainly on virilization of external genitalia (phallus size) and testosterone response (excepting 46,XX disorder of sex development). The study concludes that with meticulous clinical evaluation and base line investigations cases of disorder of sex development can be managed well
Transcervical cell (TCC) samples were retrieved between 6 and 15 weeks of pregnancy by a simple and rapid method of aspiration. The presence of fetal cells was investigated by polymerase chain reaction (PCR) assays for the amplification... more
Transcervical cell (TCC) samples were retrieved between 6 and 15 weeks of pregnancy by a simple and rapid method of aspiration. The presence of fetal cells was investigated by polymerase chain reaction (PCR) assays for the amplification of DNA sequences from chromosomes X and Y, and of polymorphic short tandem repeats (STR) specific for chromosomes 21 and 18. As judged by the detection of Y-derived PCR products, fetal cells were present in 68% of TCC samples collected from mothers with male fetuses. Paternally inherited fetal STR markers were detected in 29.6% of the tested TCC samples, while a further 44% of samples were non-informative, as the fetus had inherited markers similar to those of the mother.
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We report a case of fetal malformation detected through obstetric ultrasound examination at 27th week of pregnancy where rapid prenatal diagnosis of specific chromosomal aneuploidy (chromosome 18) was carried out on uncultured amniocytes... more
We report a case of fetal malformation detected through obstetric ultrasound examination at 27th week of pregnancy where rapid prenatal diagnosis of specific chromosomal aneuploidy (chromosome 18) was carried out on uncultured amniocytes through interphase fluorescent in situ hybridization (FISH). Parents elected to terminate the pregnancy following positive FISH result (before the availability of conventional chromosome analysis). The termination was made possible within 36 hours from amniocentesis. Ultrasound finding was suggestive of trisomy 18. Later, conventional cytogenetics confirmed FISH result and justified our approach. Our experience indicates that interphase FISH could play an important role in decision making. We conclude that rapid prenatal diagnosis of targeted chromosomal aneuploidy by interphase FISH should be offered for quick obstetric decision, especially for advanced pregnancies (beyond 20 weeks gestation).
This report presents a case of unexplained ten consecutive early third trimester intrauterine fetal deaths in the absence of any maternal detectable risk factors and in presence of normal fetal growth. Detectable associations in tenth... more
This report presents a case of unexplained ten consecutive early third trimester intrauterine fetal deaths in the absence of any maternal detectable risk factors and in presence of normal fetal growth. Detectable associations in tenth pregnancy were very low maternal serum alpha feto protein (<0.15 MOM MSAFP), turbid liquor amni and extensive placental pathology viz., fibrosis, hyalinization, infarction, narrowing as well as poor vascularization of chorionic vessels
Hydrops fetalis is defined as fluid accumulation in serous cavities of the fetus with variable degree of skin edema and with or without edematous placenta (1). Non-immunological hydrops fetalis (NIHF) is diagnosed when the cause of... more
Hydrops fetalis is defined as fluid accumulation in serous cavities of the fetus with variable degree of skin edema and with or without edematous placenta (1). Non-immunological hydrops fetalis (NIHF) is diagnosed when the cause of hydrops fetalis is other than feto-maternal blood group incompatibility (2). NIHF was first described by Potter in 1943 (3). The incidence of NIHF is reported to vary between 1 in 2500 to 3500 births (4). Numerous maternal, fetal and placental conditions can give rise to NIHF (5). However, the association of NIHF with umbilical cord true knot is reported only in few occasions (1,2,6). This report describes the necropsy study of a fetus with hydrops fetalis in association with the true knot of umbilical cord where no other causes for hydrops fetalis was apparent. A possible pathogenetic mechanism for the causation of hydrops fetalis with true cord knot has been proposed.
INTRODUCTION Cytogenetics is a branch of genetics that is devoted to the study of structure and function of cellular constituents concerned with heredity. A chromosome, as seen at metaphase, consists of two identical strands of... more
INTRODUCTION Cytogenetics is a branch of genetics that is devoted to the study of structure and function of cellular constituents concerned with heredity. A chromosome, as seen at metaphase, consists of two identical strands of chromatids. The chromatids are joined at the centromere, which appears as a constriction. The centromere divides the chromosome into a short arm (p), and a long arm (q). Individual chromosomes differ in size. Depending on the position of the centromere, chromosomes are categorised as metacentric (at the centre), submetacentric (slightly away from the centre), acrocentric (near the end) and telocentric (at the end). Human chromosomes are classified into different groups, viz., Group A (chromosome 1-3), Group B (chromosome 4-5), Group C (chromosome 6-12, X), Group D (chromosome 13-15), Group E (chromosome 16-18), Group F (chromosome 19-20) and Group G (chromosome 21-22,Y). Chromosomes of Groups D and G are acrocentric and their p arms do not contain important g...
This overview on genetic counseling for infertile couple will describe briefly genetic basis of infertility, genetic counseling of infertility, reproductive technologies used to overcome infertility, dangers of transmitting genetic... more
This overview on genetic counseling for infertile couple will describe briefly genetic basis of infertility, genetic counseling of infertility, reproductive technologies used to overcome infertility, dangers of transmitting genetic disorders to offspring, and how to prevent transmissions of genetic disorders before &/or during undergoing assisted reproduction
We have evaluated the suitability of different formalin fixed paraffin embedded tissues i.e., brain, bone, liver and placenta, for fluorescence in situ hybridization (FISH) efficiency and chromosomal ploidy detection employing directly... more
We have evaluated the suitability of different formalin fixed paraffin embedded tissues i.e., brain, bone, liver and placenta, for fluorescence in situ hybridization (FISH) efficiency and chromosomal ploidy detection employing directly labelled repetitive sequence probes for chromosome X, Y and 1. The study was carried out on four foetal autopsy specimens. Cells from 50 mu thick tissue sections were dissociated before performing mono and multicolour FISH with directly labelled probes. Hybridization efficiency was maximum with brain tissue (81, 55 and 24% for mono, dual and triple colour FISH, respectively), followed by bone (45 and 34% for mono and dual colour FISH), liver (38, 19 and 0% for mono, dual and triple colour FISH) and placenta (14, 5 and 0% for mono, dual and triple colour FISH). These results indicated that brain is the most efficient material followed by bone, liver placenta for chromosome ploidy detection by FISH in formalin fixed tissues.
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Meiotic segregation of chromosomes X,Y and 1 was analyzed by triple colour rapid fluorescent in situ hybridization (FISH) with directly labelled probes on 4506 non-decondensed and non-cleaned interphase spermatozoa from four healthy male... more
Meiotic segregation of chromosomes X,Y and 1 was analyzed by triple colour rapid fluorescent in situ hybridization (FISH) with directly labelled probes on 4506 non-decondensed and non-cleaned interphase spermatozoa from four healthy male donors to test the possibility of rapid sperm FISH by omitting the conventional sperm decondensation and cleaning steps. Only 0.15 per cent of sperms were without any signals which suggested high hybridization success. An abnormal number of signals was seen in 1.6 per cent of sperms. Chromosome specific as well as donor specific segregation error was seen similar to previous reports. There was a wide variation in the ratio of normal X and Y bearing sperm from donor to donor. This study indicated that for segregation studies sperm FISH can be carried out in three hours with directly labelled probes without the steps for separation of sperm from somatic cells (cleaning), sperm swelling and sperm DNA decondensation.
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Mature and functional Sertoli cells are essential for the survival of germ cells in testes. In Sertoli cell only syndrome (SCOS), there is no germ cells. Then, question arises whether absence of germ cells in SCOS secondary to Sertoli... more
Mature and functional Sertoli cells are essential for the survival of germ cells in testes. In Sertoli cell only syndrome (SCOS), there is no germ cells. Then, question arises whether absence of germ cells in SCOS secondary to Sertoli cells immaturity or mal function. Sertoli cells maturational and functional status is unclear in SCOS. This study investigated status of maturation and function of Sertoli cells in patients with SCOS. The present study was comprised of 37 cases of SCOS and 50 normal control males. Detailed clinical examination and investigation were carried out as per pre-determined proforma. Semen analysis, hormonal analysis (FSH, LH, testosterone, etc.), and fine needle aspiration cytology (FNAC) of testes (bilateral) were performed. Fluorescence in situ hybridization (FISH) with XY probes was carried out in addition to conventional chromosome analysis to find out chromosomal abnormalities, in particular sex chromosome aneuploidy, including mosaicism. Yq microdeletio...
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Prader Willi syndrome (PWS) most commonly is due to paternal micro-deletion of 15q11-q13. Although PWS is not a rare condition, mosaic micro-deletion cases are reported rarely. FISH using PWS micro-deletion probe is the most useful method... more
Prader Willi syndrome (PWS) most commonly is due to paternal micro-deletion of 15q11-q13. Although PWS is not a rare condition, mosaic micro-deletion cases are reported rarely. FISH using PWS micro-deletion probe is the most useful method to detect deletion including mosaicism. In this report we describe a female child with clinical features of atypical PWS and FISH analysis showing mosaicism for deletion in the PWS critical region. This is first mosaic deletion case of PWS from Indian subcontinent.
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Varying degrees of necrozoospermia are common findings in cases of male sub-fertility; however, it is rare to find persistent and 100 % necrozoospermia. A case of persistent 100 % necrozoospermia was presented in this paper, where... more
Varying degrees of necrozoospermia are common findings in cases of male sub-fertility; however, it is rare to find persistent and 100 % necrozoospermia. A case of persistent 100 % necrozoospermia was presented in this paper, where aneuploidy analysis was carried out on sperm. No known associations like thyrotoxicosis, genital infection, spinal injury and diabetes were found. Sperm fluorescent in situ hybridization (FISH) was carried out to evaluate sperm aneuploidy for chromosome 1, 9, 12, 13, 16, 18, 21, X and Y and did not show any excess of aneuploidy over controls. To the best of our knowledge, this is the first attempt on meiotic segregation analysis on 100 % necrozoospermic patients.
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A case of five and half-year-old 46,XX phenotypic male with hyper pigmented empty scrotum, penile urethra, epidi-dymis along with fallopian tubes, uterus and upper vagina as well as ovary is described. Hormonal studies were consis-tent... more
A case of five and half-year-old 46,XX phenotypic male with hyper pigmented empty scrotum, penile urethra, epidi-dymis along with fallopian tubes, uterus and upper vagina as well as ovary is described. Hormonal studies were consis-tent with the diagnosis of ...
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We report the seventh family of Fowler like syndrome (proliferative vasculopathy and hydrocephaly-hydrencephaly syndrome) and first case from Indian subcontinent. A 35 weeks extremely growth retarded male baby showed enlarged ventricles,... more
We report the seventh family of Fowler like syndrome (proliferative vasculopathy and hydrocephaly-hydrencephaly syndrome) and first case from Indian subcontinent. A 35 weeks extremely growth retarded male baby showed enlarged ventricles, thinned out cerebral cortex, diffuse intra-cerebral as well as peri-ventricular calcification, cerebral and corneal vasculopathy, unilateral micro-ophthalmia along with corneal opacity and depressed pulsatile anterior fontanel. This case was different from others concerning association with extreme oligohydramnios (in contrast to polyhydramnios), extreme growth restriction (in contrast to normal growth) and absence of gross muscle hypoplasia. No causative factors like TORCH infection, chromosomal abnormality or positive family history was noted in this case.
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Insulin/IGF-1-like signaling (IIS) plays a crucial, conserved role in development, growth, reproduction, stress tolerance, and longevity. In Caenorhabditis elegans, the enhanced longevity under reduced insulin signaling (rIIS) is... more
Insulin/IGF-1-like signaling (IIS) plays a crucial, conserved role in development, growth, reproduction, stress tolerance, and longevity. In Caenorhabditis elegans, the enhanced longevity under reduced insulin signaling (rIIS) is primarily regulated by the transcription factors (TFs) DAF-16/FOXO, SKN-1/Nrf-1, and HSF1/HSF-1. The specific and coordinated regulation of gene expression by these TFs under rIIS has not been comprehensively elucidated. Here, using RNA-sequencing analysis, we report a systematic study of the complexity of TF-dependent target gene interactions during rIIS under analogous genetic and experimental conditions. We found that DAF-16 regulates only a fraction of the C. elegans transcriptome but controls a large set of genes under rIIS; SKN-1 and HSF-1 show the opposite trend. Both of the latter TFs function as activators and repressors to a similar extent, while DAF-16 is predominantly an activator. For expression of the genes commonly regulated by TFs under rIIS...
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We report the seventh family of Fowler like syndrome (proliferative vasculopathy and hydrocephaly-hydrencephaly syndrome) and first case from Indian subcontinent. A 35 weeks extremely growth retarded male baby showed enlarged ventricles,... more
We report the seventh family of Fowler like syndrome (proliferative vasculopathy and hydrocephaly-hydrencephaly syndrome) and first case from Indian subcontinent. A 35 weeks extremely growth retarded male baby showed enlarged ventricles, thinned out cerebral cortex, diffuse intra-cerebral as well as peri-ventricular calcification, cerebral and corneal vasculopathy, unilateral micro-ophthalmia along with corneal opacity and depressed pulsatile anterior fontanel. This case was different from others concerning association with extreme oligohydramnios (in contrast to polyhydramnios), extreme growth restriction (in contrast to normal growth) and absence of gross muscle hypoplasia. No causative factors like TORCH infection, chromosomal abnormality or positive family history was noted in this case.
Research Interests:
Testicular maturation arrest is characterized by interruption of germ cell development and differentiation. Genetic factors play important role in the causation of human disease, including male infertility. The objective was to study copy... more
Testicular maturation arrest is characterized by interruption of germ cell development and differentiation. Genetic factors play important role in the causation of human disease, including male infertility. The objective was to study copy number variations in testicular maturation arrest using single nucleotide polymorphism (SNP) microarray technique. Conventional cytogenetics, targeted fluorescence in situ hybridization (FISH) and sequence-tagged site (STS) polymerase chain reaction (PCR) were used to confirm some of the SNP microarray findings. SNP microarray on 68 cases of testicular maturation arrest detected copy number variations (CNVs) mostly on sex chromosomes involving pseudoautosomal regions (PAR) 1, 2 and 3 as well as azoospermic factors (AZFs) besides three cases of chromosomal abnormalities (two Klinefelter syndromes and one case of dicentric Y). The AZF deletion was observed in 14 (20.6%) cases and the AZFc gain was observed in 6 (8.8%) cases. PAR 1 and 2 CNVs was obse...
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Background Inhibin B is a glycoprotein hormone produced mainly by granulosa cells of the ovary in early folliculogenesis. It selectively suppresses the secretion of pituitary FSH and has local paracrine actions in the gonads. Its... more
Background Inhibin B is a glycoprotein hormone produced mainly by granulosa cells of the ovary in early folliculogenesis. It selectively suppresses the secretion of pituitary FSH and has local paracrine actions in the gonads. Its measurement is useful for investigating female reproductive dysfunction. Objective The objective of this study was to examine serum levels of inhibin B in the assessment of ovarian function in patient with premature ovarian failure. Material & Method Serum from premature ovarian failure (n=34; group A), menopause (n=8; group B) and normally cycling fertile women (n=5; group C) was prospectively collected and stored at –80°C. Serum concentration of inhibin B was measured using specific solid phase sandwich ELISA. FSH level was measured using microparticle enzyme immuno assay (MEIA) for comparison. Independent sample t test was used to see the mean significance differences between groups. Results Inhibin B level was undetectable (i.e., <15pg/ml) in group A...
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Williams-Beuren syndrome (WBS) or Williams syndrome (OMIM 194050) is a multisystem disorder manifested by neurodevelopmental delay and is caused by a hemizygous deletion of ∼1.5-1.8 Mb in the 7q11.23 region. Clinical features include... more
Williams-Beuren syndrome (WBS) or Williams syndrome (OMIM 194050) is a multisystem disorder manifested by neurodevelopmental delay and is caused by a hemizygous deletion of ∼1.5-1.8 Mb in the 7q11.23 region. Clinical features include cardiovascular anomalies (mainly supravalvular aortic stenosis), peripheral pulmonary stenosis, distinctive facies, intellectual disability (usually mild), unique personality characteristics, and growth and endocrine abnormalities. Clinical diagnostic criteria are available for WBS; however, the mainstay of diagnosis is the detection of the contiguous gene deletion. Although FISH remains the most widely used laboratory test, the diagnosis can also be established by means of qPCR, MLPA, microsatellite marker analysis, and chromosomal microarray (CMA). We evaluated the utility of MLPA to detect deletion/duplication in the 7q11.23 region in 43 patients suspected to have WBS using MLPA kits for microdeletion syndromes. A hemizygous deletion in the 7q11.23 r...
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Background & objectives: Conventional cytogenetic studies have revealed more number of females in spontaneous abortion and it has been assumed that a large proportion of those were resulted from maternal contamination and overgrowth of... more
Background & objectives: Conventional cytogenetic studies have revealed more number of females in spontaneous abortion and it has been assumed that a large proportion of those were resulted from maternal contamination and overgrowth of maternal decidua in long term culture. In this study we have attempted to overcome difficulties of conventional cytogenetics by using meticulous tissue dissection and molecular methods
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Approximately 15-20 wk of clinically recognized pregnancies an: "'pontancou\ly aborted. mostly during fir ... t trimester (I). Most of the"'c ahortion ... arc carly miv..cd abortion & ancl1lbryonic pregnancy. Several... more
Approximately 15-20 wk of clinically recognized pregnancies an: "'pontancou\ly aborted. mostly during fir ... t trimester (I). Most of the"'c ahortion ... arc carly miv..cd abortion & ancl1lbryonic pregnancy. Several etiologies such a ... chrolllo\omal abnormalitie .... hOfmonal imbalances. polycystic ovarian syndrome. immunological and problems of UtCHI" hu\ been attributed (2.3). Cytogenetic study of spontaneous abortion ha... rc\calcd thaL chromm.omul abnormality i... major contributing cause in about 50-60% (4-7). Chromo\omal analy\is of aborted fetu ... b important for prognostication (8,9) because it gives information on frcqucnL:y & type of ehromo:-.omal abnormality, on etiology and risk assessment for future prcgnancie.... (5.10). Cytogcnctic evaluation of chromo~omally normal spontaneous abortion ... had gi\cn conflicting result ... about se, ratio (5.11-13). Most of the ~tudie~ indicated greater number... of female (1-J.-21). Scveral reasons for exec...
b>Objective: The objective of this study was to find out the prevalence of mullerian duct remnants in the 46 XY disorder of sex development due to disorders in androgen synthesis/action. Methods : Thirty eight cases of 46 XY disorder... more
b>Objective: The objective of this study was to find out the prevalence of mullerian duct remnants in the 46 XY disorder of sex development due to disorders in androgen synthesis/action. Methods : Thirty eight cases of 46 XY disorder of sex development of disorders in androgen synthesis/action were evaluated for diagnosis and management, including mullerian duct remnants. Mullerian ducts remnants were found in nine of them (23.7%). The diagnostic evaluation consisted of pelvic ultrasonography, genitography, cystourethroscopy, genitoscopy and laparoscopy or laparotomy. Results: The common types were an abnormally large prostatic utricle communicating with the urethra and a rudimentary uterus. Conclusion: It is concluded that mullerian ducts remnants are common with the 46 XY disorder of sex development due to disorders in androgen synthesis/action. During evaluation of patients, this aspect should be kept in mind and during management, appropriate measures should be undertaken to ...
Recent studies highlighted the potential risks of major birth defect in IVF pregnancy as well as IVF-ICSI pregnancies in comparison to naturally conceived pregnancies. This increased risk could be due to either gonadotropins used for... more
Recent studies highlighted the potential risks of major birth defect in IVF pregnancy as well as IVF-ICSI pregnancies in comparison to naturally conceived pregnancies. This increased risk could be due to either gonadotropins used for ovarian stimulation or in vitro culture conditions or multiple pregnancy or combinations of all the factors. It is postulated that exogenously administered high dose of gonadotropins results in very high concentration of circulating steroids that may have influence on oocytes leading to excess abnormality in embryos. Due to difficulties (technical as well as ethical) in obtaining naturally fertilized eggs (preimplantation embryos), identical population and identical environmental condition it seems difficult to assess effect of gonadotropin in inducing excess anomalies in human. Furthermore, human IVF pregnancies mainly from infertile couples with advanced maternal age that itself is a risk factor for increased chromosome aneuploidy. Additionally it is ...
Objective: The objective of the study was to determine whether noninvasive and readily available cells could be used for rapid diagnosis of specific chromosomal abnormality to facilitate management of patients in acute/specialized... more
Objective: The objective of the study was to determine whether noninvasive and readily available cells could be used for rapid diagnosis of specific chromosomal abnormality to facilitate management of patients in acute/specialized situation. Methods: In the present study we analyzed blood, buccal & urine cells from 3 patients with pure trisomy 21 with locus specific FISH probes for chromosome 21. Three normal subjects were included for comparison. The clinical cases were confirmed with conventional cytogenetic studies of peripheral lymphocytes before inclusion in the study. Result: Average frequencies for 1, 2 and 3 hybridization signals were 2.2%, 6% and 91% for blood cells, 2.5%, 7% and 89.8% for buccal cells and 2%, 9.3% and 87.4% for urine cells, respectively in the cases. False trisomic cells were less than 1% in all type of cells in controls. False monosomic cells were 3.6%, 4.5% & 9.8% for blood, buccal & urine cells in controls which was quite similar to alphoid FISH probes ...
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Advances in the field of cytogenetics, largely, have been technology driven. We have witnessed multiple waves of progression starting with accidental discovery of hypotonic saline to the current era of molecular cytogenetics. The new wave... more
Advances in the field of cytogenetics, largely, have been technology driven. We have witnessed multiple waves of progression starting with accidental discovery of hypotonic saline to the current era of molecular cytogenetics. The new wave is now on chromosome analysis from microscope to automated microarray (molecular karyotyping) for identification of chromosomal abnormality beyond cytogenetic resolution. The days are not far when microarray based molecular karyotyping would become the primary choice to direct analysis of all chromosomes/genes/portion of genes in one action, without subjective nature and difficult cell culture, the real replacement of conventional cytogenetics for most purpose and without restriction to cytogenetic experts. The proposed workshop has been planned to provide an exposure to molecular cytogenetics: Reproductive genetics by fluorescent in situ hybridization (FISH), Primed In Situ Labeling (PRINS) and Polymerase Chain Reaction (PCR). Besides few lectures...
Sex ratio can be studied at various levels viz., at the time of spermatogenesis i.e. ratio of X and Y bearing sperm (pre-zygotic sex ratio) or at the time of fertilization/early preimplantation embryo (close to primary sex ratio or... more
Sex ratio can be studied at various levels viz., at the time of spermatogenesis i.e. ratio of X and Y bearing sperm (pre-zygotic sex ratio) or at the time of fertilization/early preimplantation embryo (close to primary sex ratio or post-zygotic sex ratio) or at the time of birth (secondary sex ratio). The natural sex ratio at the time of spermatogenesis is expected to be 1:1. In this study we have examined sex ratio in ejaculated spermatozoa (human) as well as epididymal sperm (mouse) to determine proportion of X and Y bearing sperm i.e., pre-zygotic sex ratio. We also examined effects of seasons (temperature; summer vs. winter), diet (vegetarian vs. non vegetarian), profession (professionals vs. laborer) on sperm (pre-zygotic) sex (X: Y) ratio of ejaculated sperm. The sperm sex ratio was carried out on 813066 human spermatozoa and 10390 mouse spermatozoa. In human, we have found more (52%) X than Y (48%) bearing sperms (421531X: 391535Y or 1.07X: 1Y). In mouse also we observed prep...
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Conventional cytogenetic studies have revealed more number of females in spontaneous abortion and it has been assumed that a large proportion of those were resulted from maternal contamination and overgrowth of maternal decidua in long... more
Conventional cytogenetic studies have revealed more number of females in spontaneous abortion and it has been assumed that a large proportion of those were resulted from maternal contamination and overgrowth of maternal decidua in long term culture. In this study we have attempted to overcome difficulties of conventional cytogenetics by using meticulous tissue dissection and molecular methods onto uncultured chorionic villous tissue thus bypassing long term culture to find out true sex ratio and frequency as well as type of common aneuploidy in early missed abortions. Early missed abortion products (n=58) were collected from recurrent aborter in and around Lucknow, India, over a period of three years. All the cases were selected on the basis of ultrasonography diagnosis. Chorionic villous tissue was cleaned from maternal tissue and processed for conventional as well as molecular cytogenetic analysis. Conventional cytogenetics was successful in 15, of which 12 were females and 3 male...
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Available clinical, radiological and histopathologic risk factors are not adequate for accurate prognosis in uterine cervix carcinoma. Hence there is a need to identify indicators to select high risk cases. Most cancers occur and progress... more
Available clinical, radiological and histopathologic risk factors are not adequate for accurate prognosis in uterine cervix carcinoma. Hence there is a need to identify indicators to select high risk cases. Most cancers occur and progress through step-wise somatic genetic mutations. Thus screening of whole genome for specific genomic alterations and its outcome following treatment may predict prognosis. The present study was carried out to investigate genomic alterations associated with cervical carcinoma and any association of genomic alterations with clinico-pathologic parameters. Cervical carcinoma cases (n = 4) were subjected to protocol based clinical evaluation, treatment and follow up as a double blind procedure. Tumour samples were collected before radiotherapy and 3 months after completion of radiotherapy. All the samples were stored at -80 degrees C. Comparative genomic hybridization (CGH) was carried out to screen genomic alterations in all tumour samples obtained before ...
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We report an eight years female child with clinical and molecular cytogenetic findings consistent with CATCH 22 syndrome characterized by cardiac defect, typical facial dysmorphism, mental deficiency and chromosome 22 q11.2 deletion.... more
We report an eight years female child with clinical and molecular cytogenetic findings consistent with CATCH 22 syndrome characterized by cardiac defect, typical facial dysmorphism, mental deficiency and chromosome 22 q11.2 deletion. Interphase FISH with 22q 11.2 probe demonstrated hemizygous deletion in 98.5% nuclei. Interphase FISH for diagnosis of CATCH 22 syndrome has not been reported previously from India to our knowledge.
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Research Interests: Hydrocephalus, Pregnancy, Humans, Female, Male, and 6 moreInfant, Prognosis, Neural Tube Defects, Thoracic Vertebrae, Syndrome, and Ribs
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Microdeletion syndromes are characterized by small (<5 Mb) chromosomal deletions in which one or more genes are involved. These are frequently associated with multiple congenital anomalies. The phenotype is the result of... more
Microdeletion syndromes are characterized by small (<5 Mb) chromosomal deletions in which one or more genes are involved. These are frequently associated with multiple congenital anomalies. The phenotype is the result of haploinsufficiency of genes in the critical interval. Fluorescence in situ hybridization (FISH) technique is commonly used for precise genetic diagnosis of microdeletion syndromes. This study was conducted to assess the role of FISH in the diagnosis of suspected microdeletion syndrome. FISH was carried out on 301 clinically suspected microdeletion syndrome cases for the confirmation of clinical diagnosis using non-commercial probes. Of these, 177 cases were referred for 22q11.2 microdeletion, 42 cases were referred for William syndrome, 38 cases were referred for Prader Willi/Angelman and 44 cases were referred for other suspected microdeletion syndromes. FISH was confirmatory in 23 cases only (7.6%). There were 17 cases of 22q11.2 microdeletion, four cases of Pr...
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Varying degrees of necrozoospermia are common findings in cases of male sub-fertility; however, it is rare to find persistent and 100 % necrozoospermia. A case of persistent 100 % necrozoospermia was presented in this paper, where... more
Varying degrees of necrozoospermia are common findings in cases of male sub-fertility; however, it is rare to find persistent and 100 % necrozoospermia. A case of persistent 100 % necrozoospermia was presented in this paper, where aneuploidy analysis was carried out on sperm. No known associations like thyrotoxicosis, genital infection, spinal injury and diabetes were found. Sperm fluorescent in situ hybridization (FISH) was carried out to evaluate sperm aneuploidy for chromosome 1, 9, 12, 13, 16, 18, 21, X and Y and did not show any excess of aneuploidy over controls. To the best of our knowledge, this is the first attempt on meiotic segregation analysis on 100 % necrozoospermic patients.
Research Interests: Humans, Meiosis, Male, Aneuploidy, Clinical Sciences, and 4 moreAdult, Necrosis, Chromosome segregation, and Spermatozoa
Chromosome aneuploidy plays an important role in infertility, early pregnancy wastage and perinatal mortality. Cytogenetic & fluorescent in situ hybridization (FISH) studies on developmentally arrested and morphologically poor embryo have... more
Chromosome aneuploidy plays an important role in infertility, early pregnancy wastage and perinatal mortality. Cytogenetic & fluorescent in situ hybridization (FISH) studies on developmentally arrested and morphologically poor embryo have shown high frequency of chromosomal abnormality and mosaicism. In this study, we attempted to evaluate chromosome aneuploidy and mosaicism on human embryos through the use of FISH. Sixty one grade IV un-transferable embryos were obtained from 25 patients undergoing in vitro fertilization (IVF). Forty six embryos were studied by FISH; 15 were lost during transport and handling. FISH probes (non-commercial) for centromeres of chromosome X, Y, 1 and 18 were used for the study. Zona of embryos were dissolved in 0.01N HCl containing 0.1 per cent Tween 20 for 2-3 min. Interpretable FISH results were obtained in 24 embryos. Nineteen embryos (79.2%) were disomic (normal) for chromosome X/Y or 1/18 and five (20.8%) were abnormal. Among five abnormal embryos...
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There are potential risks of major birth defect in IVF (in vitro fertilization) pregnancy as well as IVF-ICSI (intra cytoplasmic sperm injection) pregnancies in comparison with naturally conceived human pregnancies. This increase risk... more
There are potential risks of major birth defect in IVF (in vitro fertilization) pregnancy as well as IVF-ICSI (intra cytoplasmic sperm injection) pregnancies in comparison with naturally conceived human pregnancies. This increase risk could be due to either gonadotropins used for ovarian stimulation or in vitro culture conditions or multiple pregnancy or combinations of all the factors. The effects of gonadotropins on chromosome aneuploidy, chromosome mosaicism and sex ratio on mouse preimplantation embryos were evaluated through the use of fluorescence in situ hybridization (FISH). The study material consisted of 111 preimplantation mouse embryos (2-16 cell stage) in control group and 405 preimplantation mouse embryos in gonadotropin stimulated group from genetically identical Swiss Albino young (6-8 wk) mouse kept in a similar environmental conditions. The study was designed to investigate effect of gonadotropins on chromosome aneuploidy, chromosome mosaicism and sex ratio through...