Ali A, Babar ME, Kalsoom S
… +2 more, Ahmad J, Abbas K
Indian J Hum Genet
· 2013 Jul · PMID 24339546
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BACKGROUND: Hearing disorders represent a significant health problem worldwide. Recessive inherited cases of the deafness are more prevalent in Pakistan due to consanguineous marriages. Deafness caused by DFNB3 is due to...BACKGROUND: Hearing disorders represent a significant health problem worldwide. Recessive inherited cases of the deafness are more prevalent in Pakistan due to consanguineous marriages. Deafness caused by DFNB3 is due to mutation in the gene MYO XVA and its prevalence among Pakistani population is about 5%. MATERIALS AND METHODS: Families with at least two or more individual affected with deafness were selected from different areas of District Okara of Pakistan. Six consanguineous families of different ethnic groups having deaf individuals were studied. All these families had three or more deaf individuals in either two or more sib ships. Family history was taken to minimize the chances of other abnormalities. Pedigrees drawn by using Cyrillic software (version 2.1) showed that all the marriages were consanguineous and the families have recessive mode of inheritance. Three STR markers were selected and amplified on all the samples of six families through PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE). Haplotypes were constructed to determine the pattern of inheritance and also to determine whether a family was linked or unlinked with known DFNB3 locus. RESULTS: One out of six families showed linkage to the DFNB3 while rest of the families remained unlinked. Carriers of deafness genes were identified and information was provided to the families on request. CONCLUSION: Knowledge about the genetic causes of deafness provide insight into the variable expression of genes involved in this hereditary problem and may allow the prediction and prevention of associated health problems.
Indian J Hum Genet
· 2013 Jul · PMID 24339545
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Mitochondria contains a single deoxyribonucleic acid (DNA) polymerase, polymerase gamma (POLG) mapped to long arm of chromosome 15 (15q25), responsible for replication and repair of mitochondrial DNA. Exon 1 of the human...Mitochondria contains a single deoxyribonucleic acid (DNA) polymerase, polymerase gamma (POLG) mapped to long arm of chromosome 15 (15q25), responsible for replication and repair of mitochondrial DNA. Exon 1 of the human POLG contains CAG trinucleotide repeat, which codes for polyglutamate. Ten copies of CAG repeat were found to be uniformly high (0.88) in different ethnic groups and considered as the common allele, whereas the mutant alleles (not -10/not -10 CAG repeats) were found to be associated with oligospermia/oligoasthenospermia in male infertility. Recent data suggested the implication of POLG CAG repeat expansion in infertility, but are debated. The aim of our study was to explore whether the not -10/not -10 variant is associated with spermatogenic failure. As few study on Indian population have been conducted so far to support this view, we investigated the distribution of the POLG CAG repeats in 61 infertile men and 60 normozoospermic control Indian men of Tamil Nadu, from the same ethnic background. This analysis interestingly revealed that the homozygous wild type genotype (10/-10) was common in infertile men (77% - 47/61) and in normozoospermic control men (71.7% - 43/60). Our study failed to confirm any influence of the POLG gene polymorphism on the efficiency of the spermatogenesis.
Indian J Hum Genet
· 2013 Jul · PMID 24339544
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BACKGROUND: In order to understand how selection is operating in the Gowda population, the index of opportunity for selection was calculated and the present findings were compared with some related findings from other So...BACKGROUND: In order to understand how selection is operating in the Gowda population, the index of opportunity for selection was calculated and the present findings were compared with some related findings from other South Indian (SI) populations. MATERIALS AND METHODS: Crow (1958) and the modified method by Johnston and Kensinger (1971) were used for the present purpose. RESULTS AND DISCUSSION: The index of total selection intensity (I) was found to be moderate taking into consideration the range for many Indian populations. Considering certain differences in fertility and mortality heritable, it appears that natural selection play an important role in shaping the genetic constitution of the Gowda population. Analysis of data indicates that the index due to fertility seems to contribute more towards selection than mortality. This trend might be because of better living condition and health-care system among the Gowdas which have a positive impact on the lower contribution of mortality for the evolution mechanism of the Gowda population through natural selection.
Indian J Hum Genet
· 2013 Jul · PMID 24339543
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CONTEXT: Alterations in the human chromosomal complement are expressed phenotypically ranging from (i) normal, via (ii) frequent fetal loss in otherwise normal person, to (iii) sub-clinical to severe mental retardation a...CONTEXT: Alterations in the human chromosomal complement are expressed phenotypically ranging from (i) normal, via (ii) frequent fetal loss in otherwise normal person, to (iii) sub-clinical to severe mental retardation and dysmorphism in live births. A subtle and microscopically undetectable chromosomal alteration is uniparental disomy (UPD), which is known to be associated with distinct birth defects as per the chromosome involved and parental origin. UPD can be evident due to imprinted genes and/or activation of recessive mutations. AIMS: The present study comprises of data mining of published UPD cases with a focus on associated phenotypes. The goal was to identify non-random and recurrent associations between UPD and various genetic conditions, which can possibly indicate the presence of new imprinted genes. SETTINGS AND DESIGN: Data mining was carried out using the homepage "http://www.fish.uniklinikum-jena.de/UPD.html.", an online catalog of published cases with UPD. MATERIALS AND METHODS: The UPD cases having normal karyotype and with or without clinical findings were selected to analyze the associated phenotypes for each chromosome, maternal or paternal involved in UPD. RESULTS: Our results revealed many genetic conditions (other than the known UPD syndromes) to be associated with UPD. Even in cases of bad obstetric history as well as normal individuals chance detection of UPD has been reported. CONCLUSIONS: The role of UPD in human genetic disorders needs to be studied by involving larger cohorts of individuals with birth defects as well as normal population. The genetic conditions were scrutinized in terms of inheritance patterns; majority of these were autosomal recessive indicating the role of UPD as an underlying mechanism.
Kumar DK, Shewade DG, Manjunath S
… +3 more, Ushakiran P, Reneega G, Adithan C
Indian J Hum Genet
· 2013 Jul · PMID 24339542
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BACKGROUND: Genetic variation in the vitamin K epoxide reductase complex (VKORC1) and cytochrome P450 4F2 (CYP4F2) genes were found to be strongly associated with the oral anticoagulant (OA) dose requirement. The distrib...BACKGROUND: Genetic variation in the vitamin K epoxide reductase complex (VKORC1) and cytochrome P450 4F2 (CYP4F2) genes were found to be strongly associated with the oral anticoagulant (OA) dose requirement. The distribution of genetic variation in these two genes was found to show large inter- and intra-ethnic difference. MATERIALS AND METHODS: A total of 470 unrelated, healthy volunteers of South Indians of either sex (age: 18-60 years) were enrolled for the study. A 5 ml of venous blood was collected and the genomic deoxyribonucleic acid (DNA) was extracted by using phenol-chloroform extraction method. Real-time quantitative polymerase chain reaction (RT-PCR) method was used for genotyping. RESULTS: The variant allele frequencies of VKORC1 rs2359612 (T), rs8050894 (C), rs9934438 (T) and rs9923231 (A) were found to be 11.0%, 11.8%, 11.7% and 12.0%, respectively. The variant allele VKORC1 rs7294 was (80.1%) more frequent and the variant allele CYP4F2 * 3 was found to be 41.8% in South Indians. The allele, genotype and haplotype frequencies of VKORC1 and CYP4F2 gene were distinct from other compared HapMap populations (P < 0.0001). CONCLUSION: The findings of our study provide the basic genetic information for further pharmacogenetic based investigation of OA therapy in the population.
Indian J Hum Genet
· 2013 Jul · PMID 24339541
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BACKGROUND AND AIM: p73, a novel P53 homolog and plays an important role in modulating cell cycle control, apoptosis and cell growth while P21, functions to negatively control the cell cycle. P53 up regulates p21 express...BACKGROUND AND AIM: p73, a novel P53 homolog and plays an important role in modulating cell cycle control, apoptosis and cell growth while P21, functions to negatively control the cell cycle. P53 up regulates p21 expression in response to deoxyribonucleic acid damage leading to cell cycle arrest at G1 checkpoint. In the present study, we are targeting p21 codon 31 and p73 gene variants of G4C14-to-A4T14 (Exon 2) polymorphism for bladder cancer (BC) risk in North Indians. MATERIALS AND METHODS: The above gene variants of P21 and P73 were assessed in the case-control study comprising of 200 BC cases and 200 healthy controls of the same age, gender and similar ethnicity. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism method and PCR-based confronting two-pair primers (PCR with CTPP). RESULTS: The variant genotype of p73Exon 2 polymorphism showed significant risk for BC (p = 0.014). While combining with heterozygous genotype, variant genotype of p73Exon2 showed a significant association with BC risk (p = 0.010). While in case of p21 codon31 showed no significant association for BC risk at genotypic level. Significant association between p73Exon2 polymorphism and smoking was observed for BC risk. Furthermore, gene combination analysis revealed that AT/AT-Ser/Ser is associated with risk for BC. Variant genotype of P73Exon2 was associated with reduced risk of recurrence (p = 0.039) in superficial BC patients receiving Bacillus Calmette-Guerin treatment thus showing least survival (log rank = 0.029). CONCLUSION: Our study provided evidence that the p73 G4C14 > A4T14 (Exon2) polymorphisms were associated with higher risk of BC in North Indian population.
Indian J Hum Genet
· 2013 Jul · PMID 24339540
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BACKGROUND: Hemoglobin (Hb) D Punjab disorder is a congenital hemoglobinopathy described in India. It is a disorder due to defect in beta-globin gene. MATERIALS AND METHODS: Here, the author assesses the possibility of U...BACKGROUND: Hemoglobin (Hb) D Punjab disorder is a congenital hemoglobinopathy described in India. It is a disorder due to defect in beta-globin gene. MATERIALS AND METHODS: Here, the author assesses the possibility of U7.623 gene therapy for Hb D Punjab disorder. A standard bioinformatic analysis to study the effect of co-expression between nucleic acid sequence for human Hb D Punjab beta-globin chain and U7.623 was performed. RESULT: It can be seen that fully recovery of Hb function and biological process can be derived via gene ontology study. CONCLUSION: Here, there is a rationale to use U7 small nuclear ribonucleic acid as a possible tool for gene therapy in Hb D Punjab disorder.
Indian J Hum Genet
· 2013 Jul · PMID 24339539
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Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatme...Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.
Indian J Hum Genet
· 2013 Jul · PMID 24339538
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Hemoglobin E (Hb E) disorder is an important kind of hemoglobinopathy. It can be seen around the world with the highest prevalence in Southeast Asia. The screening for this disorder becomes the public health policies in...Hemoglobin E (Hb E) disorder is an important kind of hemoglobinopathy. It can be seen around the world with the highest prevalence in Southeast Asia. The screening for this disorder becomes the public health policies in many countries. The screening can be performed in several population groups. The newborn screening program for Hb E disorder is an important issue in pediatric genetics. In this brief review, the author discusses on important laboratory tests for screening for Hb E disorder in newborn.
Indian J Hum Genet
· 2013 Apr · PMID 24019634
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Sclerosteosis or Truswell-Hansen disease is a rare autosomal recessive disorder characterized by dense bones, tall stature, and syndactyly. Most of the reports are from South Africa. Here we report the first such case fr...Sclerosteosis or Truswell-Hansen disease is a rare autosomal recessive disorder characterized by dense bones, tall stature, and syndactyly. Most of the reports are from South Africa. Here we report the first such case from India.
Indian J Hum Genet
· 2013 Apr · PMID 24019633
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Kartagener's syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. Primary ciliary dyskinesia is a genetic disorder with manifestations present fro...Kartagener's syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. Primary ciliary dyskinesia is a genetic disorder with manifestations present from early life and this distinguishes it from acquired mucociliary disorders. Approximately one half of patients with primary ciliary dyskinesia have situs inversus and, thus are having Kartagener syndrome. We present a case of 12 year old boy with sinusitis, situs inversus and bronchiectasis. The correct diagnosis of this rare congenital autosomal recessive disorder in early life is important in the overall prognosis of the syndrome, as many of the complications can be prevented if timely management is instituted, as was done in this in this case.
Indian J Hum Genet
· 2013 Apr · PMID 24019632
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The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to...The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to emphasize the importance of parental karyotyping. Cytogenetic evaluation of the proband and his father were carried out at Laboratory. Cytogenetic analysis was performed on phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband was ascertained to have additional material from chromosome 6p arising from complex chromosomal rearrangement in the father. Karyotyping is the basic, cost-effective preliminary investigation in a child with mental subnormality or congenital anomalies.
Indian J Hum Genet
· 2013 Apr · PMID 24019631
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Since the aggregate incidence of inborn errors of metabolism is relatively high, a high degree of suspicion is essential to correctly diagnose an inborn error of amino acid metabolism. We report a case of alkaptonuria an...Since the aggregate incidence of inborn errors of metabolism is relatively high, a high degree of suspicion is essential to correctly diagnose an inborn error of amino acid metabolism. We report a case of alkaptonuria an autosomal recessive disorder that occurs due to deficiency of homogentisic acid oxidasein a β-thalassemia infant presenting with reddish discoloration of nappies and clothes, breath holding spells, and microcytic hypochromic anemia. Born to consanguineous cousins, to our knowledge, the combination of β-thalassemia and alkaptonuria, which we have described in this baby, has not been reported earlier.
Italia K, Jijina F, Merchant R
… +5 more, Swaminathan S, Nadkarni A, Gupta M, Ghosh K, Colah R
Indian J Hum Genet
· 2013 Apr · PMID 24019630
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BACKGROUND: Hydroxyurea, which induces Fetal hemoglobin (HbF) synthesis, is the only drug widely used in different hemoglobinopathies; however, the response is very variable. We compared the efficacy of hydroxyurea in-vi...BACKGROUND: Hydroxyurea, which induces Fetal hemoglobin (HbF) synthesis, is the only drug widely used in different hemoglobinopathies; however, the response is very variable. We compared the efficacy of hydroxyurea in-vitro in erythroid cultures and in-vivo in the same patients with different hemoglobinopathies to induce HbF production and enhance γ-messenger RNA expression. MATERIALS AND METHODS: A total of 24-patients with different Hemoglobinopathies were given hydroxyurea and their response was studied in-vivo and in-vitro on mononuclear cells collected from them simultaneously. RESULTS: A total of 57.7% of patients (responders) showed no further crisis or transfusion requirements after hydroxyurea therapy with a mean increase in fetal cells (F-cells) of 63.8 ± 59.1% and γ-mRNA expression of 205.5 ± 120.8%. In-vitro results also showed a mean increase in F-cells of 27.2 ± 24.7% and γ-mRNA expression of 119.6% ± 65.4% among the treated cells. Nearly 19.0% of the partial-responders reduced their transfusion requirements by 50% with a mean increase in F-cells of 61.2 ± 25.0% and 28.4 ± 25.3% and γ-mRNA-expression of 21.0% ± 1.4% and 80.0% ± 14.1% in-vivo and in-vitro respectively. The non-responders (15.3%) showed no change in their clinical status and there was no significant increase in F-cells levels and γ-mRNA expression in-vivo or in-vitro. CONCLUSION: Thus, this method may help to predict the in-vivo response to hydroxyurea therapy; however, a much larger study is required.
Indian J Hum Genet
· 2013 Apr · PMID 24019629
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INTRODUCTION: Menarche or first menstrual period is a landmark in reproductive life span and it is the most prominent change of puberty. The timing of menarche can be under the influence of genes as well as individual en...INTRODUCTION: Menarche or first menstrual period is a landmark in reproductive life span and it is the most prominent change of puberty. The timing of menarche can be under the influence of genes as well as individual environmental factors interacting with genetic factors. OBJECTIVE: Our study objectives were (a) to investigate the heritability of age of menarche in twins, (b) to obtain the association between age of menarche and childhood factors, and reproductive events/behavior, (c) to examine whether or not having a male co-twin affects early/late menarche. METHODOLOGY: A group of female-female identical (n = 108, 54 pairs), non-identical twins (n = 68, 34 pairs) and 17 females from opposite-sex twin sets were identified from twin registries of Malaysia and Iran. Genetic analysis was performed via two methods of Falconers' formula and maximum likelihood. RESULTS: Heritability was found to be 66% using Falconers' formula and 15% using univariate twin analysis. Model analysis revealed that shared environmental factors have a major contribution in determining the age of menarche (82%) followed by non-shared environment (18%). DISCUSSION: Result of this study is consistent with that of the literature. Timing of menarche could be under the influence of shared and non-shared environmental effects. Hirsutism was found to have a higher frequency among subjects with late menarche. There was no significant difference in age of menarche between females of opposite-sex twins and females of same-sex twins. CONCLUSION: It is concluded that twin models provide a powerful means of examining the total genetic contribution to age of menarche. Longitudinal studies of twins may clarify the type of environmental effects that determine the age of menarche.
Motavallian A, Andalib S, Vaseghi G
… +2 more, Mirmohammad-Sadeghi H, Amini M
Indian J Hum Genet
· 2013 Apr · PMID 24019628
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BACKGROUND: Peroxisome proliferator-activated receptor (PPARs) have been identified as ligand-activated transcription factors that belong to the nuclear receptor superfamily. It has been shown that an association exists...BACKGROUND: Peroxisome proliferator-activated receptor (PPARs) have been identified as ligand-activated transcription factors that belong to the nuclear receptor superfamily. It has been shown that an association exists between Proline 12 alanine (Pro12Ala) polymorphism of PPAR-GAMMA2 (PPAR-γ2) gene and increased risk of type 2 diabetes mellitus (T2DM) in different populations. Therefore, the present study was designed to investigate the association between Pro12Ala polymorphism of PPAR-γ2 gene and T2DM in an Iranian population. MATERIALS AND METHODS: Two hundred unrelated people, including 100 healthy controls and 100 diabetic patients were recruited diagnosed based on American Diabetes Association criteria. Blood samples were used for isolation of genomic deoxyribonucleic acid (DNA). Having extracted the genomic DNA from human blood leukocytes by means of High Pure polymerase chain reaction (PCR) Template preparation kit, we carried out polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on each blood sample. Then, Genomic DNA was digested by BstU-I restriction enzyme. Thereafter, restriction products were analyzed by means of Polyacrylamide gel electrophoresis and stained by Ethidium Bromide. RESULTS: We found that the frequency of Ala allele in healthy subjects was significantly higher than in diabetic subjects (P = 0003). Moreover, the genotype frequency of Ala/Ala in healthy subjects was significantly higher than in diabetic subjects (P < 0.001). However, the genotype frequency of Ala/Pro in diabetic subjects was significantly higher than in healthy subjects (P < 0.001). CONCLUSION: The present study suggests that polymorphism of PPAR-γ2 gene is associated with T2DM. Furthermore, Ala allele is significantly found in non-diabetic individual's Iranian population.