Advancement in the molecular tools used in toxicology has provided immense information about the cellular and global structure and function of toxicant-responsive genes. Now, it has become possible to assess the functional activity of genes and proteins involved in various toxicological pathways, which were not possible with the conventional methods. Many genes are known to have a greater influence on the susceptibility to environmental agents than others; therefore, identification and characterization of polymorphism in such genes for the determination of early, late, or no response of an individual for the toxicant-induced diseases has also become mandatory. Toxicogenomics, a newly born discipline of toxicology, comprises of two major facets, one, how various genes in the genome respond to environmental toxicants and stressors and second, how toxicants modify the function and expression of specific genes in the genome. Toxicogenomics play an important role in the identification and characterization of molecular biomarkers to predict cellular toxicity and to determine the efficacy and exposure in the toxicity trials at an early stage. Genome and proteome-wide expression profiles in combination with conventional toxicology are being used to classify compounds, predict the mechanism of toxicity of newer compounds and determine the susceptibility of an individual for the toxic responses. Single-nucleotide polymorphism in toxicant-responsive genes is being used to obtain basic information of the genetic variation and its role in the functional protein expression. Various national and international government and private organizations have launched several programs on gene-environment interactions. Council of Scientific and Industrial Research (CSIR), New Delhi, India, has also launched a program on 'toxicogenomics of genetic polymorphism in Indian population to industrial chemicals for development of biomarkers' to provide better ventures and facilities to researchers in order to understand the environment-genome interactions. In this review, the contribution of genomics, proteomics, and SNPs in toxicology along with its current status in India has been discussed

BACKGROUND : β -Thalassemia (β -thal) is present in practically every caste group in Indians. Molecular characterization of β -thal in these groups has revealed an extremely heterogeneous picture. AIM : To identify all the mutations and to detect the novel mutations using a versatile mutation detection technique. MATERIALS AND METHODS : Denaturing gradient gel electrophoresis (DGGE) has been established to scan the entire β -globin gene to localize the mutation followed by DNA sequencing for characterization. The DNA samples from two families referred to us either for prenatal diagnosis or for DNA studies were studied. RESULTS : Atypical DGGE patterns in fragments B & A indicating the presence of the mutation, have been detected in both the families. DNA sequencing revealed two rare patterns fragments with patterns in fragments β -thal mutations [CD 26 (C®T) and -90 (C®T)]. CONCLUSION : DGGE is a useful mutation detection technique to identify β -thal mutations among the heterogeneous Indian population.

BACKGROUND : Faisalabad is the third biggest city of Pakistan. Majority of the population is Punjabi while other ethnic groups are in minority. AIMS : The present study was undertaken to find the mutations causing β -thalassemia in Faisalabad Pakistan. MATERIALS AND METHODS : A total of 285 β -globin alleles from 143 unrelated families having at least one transfusion-dependent child were analyzed by using amplification refractory mutation system (ARMS-PCR). RESULTS : FSC-8/9 (+G) and IVS-I-5 (G ®C) were the most common mutations. The allele frequency for FSC-8/9 (+G) was 38.59% while frequency for IVS-I-5 (G ®C) was 37.89%. The high frequency (76.48%) of IVS-I-5 (G ®C) and FSC-8/9 (+G) on various alleles provides a strong evidence of intermarriages. CONCLUSIONS : By using ARMS-PCR, the mutations were successfully characterized in 95.79% of subjects, while 4.21% remain to be characterized. This study will facilitate the implementations of genetic counseling and prenatal diagnosis in the population of Faisalabad.

Background0 : Human chimerism is rare and usually uncovered through investigations of ambiguous genitalia or blood grouping or prenatal diagnosis. Most of the publications on placental chimerism are mainly case reports. There is no systematic search with sensitive techniques for placental chimerism in human. Aim0 : This study was aimed to asses placental chimerism through two sensitive molecular techniques i.e., interphase fluorescent in situ hybridization and quantitative fluorescent PCR. Material and methods0 : Placental chimerism was analyzed using X & Y dual color fluorescent in-situ hybridization onto 154 placentae from natural conceptions, obtained at termination of pregnancy between 7 to 16 weeks of gestation. Results0 : Three cases of placental sex chromosome chimerism were observed (1.95%). Exclusion of maternal contamination and diagnosis was confirmed later by quantitative fluorescent PCR. Conclusion0 : This finding indicates that placental chimerism in early human pregnancy is not rare.

BACKGROUND : Previous studies have suggested that Glutathione S -transferase (GST) genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In different ethnic groups variations in null allele frequency has been observed. AIMS: We aimed to evaluate whether genetic polymorphisms of Glutathione S -transferase theta (GSTT1) influence individual susceptibility to lung cancer in Turkish population. We tried to clarify the frequencies of GSTM1 gene polymorphisms in a Turkish population. METHODS: DNA samples, extracted from the whole blood were amplified using polymerase chain reaction (PCR) method in all of the 68 cases, composed of 31 previously diagnosed lung cancer and 37 healthy controls. RESULTS: The prevalence of GSTT1 null genotype in the lung cancer patients was 29%, compared to 11% in control group. GSTT1 null genotype was found to be higher in cancer group compared to the control group, although it was not statistically significant (OR = 3.37, 95% CI = 0.92-12.32, P = 0.06). There was also no significant relation in GSTT1 genotypes among histopathology types of lung cancers. The frequency of GSTT1 was found to be 25.4% ( n = 952) when the studies of Turkish population were reviewed. CONCLUSION: It can be concluded that carrying the GSTT1 null genotype may be accepted as a weak risk factor for the susceptibility to lung cancer.

BACKGROUND: First trimester pregnancy loss is a very common complication and a matter of concern for couples planning pregnancy. Balanced chromosomal rearrangements in either parent is an important cause of recurrent pregnancy loss particularly in the first trimester. AIMS: In this study an evaluation of the contribution of chromosomal anomalies in causing repeated spontaneous abortions was made. METHODS AND MATERIALS: A review of the cytogenetic data in 742 couples (1484 individuals) with recurrent spontaneous abortions who were examined for chromosomal aberrations in the period 1990-2003 is presented. Women who had at least two abortions, or spontaneous abortions preceded or followed by fetal deaths or birth of a malformed child, and patients who had recurrent spontaneous abortions (> 3) with normal live issue/s were studied. RESULTS: Chromosomal rearrangements were found in 31 individuals (2%). These abnormalities included 22 (2.9%) structural aberrations, 9 (1.2%) numerical anomalies. In addition to these abnormalities, 21 (3.2%) chromosomal variants were also found. CONCLUSION: Chromosomal analysis is an important etiological investigation in couples with repeated spontaneous abortions as it helps in genetic counseling and deciding about further reproductive options.

BACKGROUND: The impact of microwave (MW)/radio frequency radiation (RFR) on important biological parameters is probably more than a simply thermal one. Exposure to radio frequency (RF) signals generated by the use of cellular telephones have increased dramatically and reported to affect physiological, neurological, cognitive and behavioural changes and to induce, initiate and promote carcinogenesis. Genotoxicity of RFR has also been reported in various test systems after in vitro and/or in vivo exposure but none in mobile phone users. AIMS: In the present study, DNA and chromosomal damage investigations were carried out on the peripheral blood lymphocytes of individuals using mobile phones, being exposed to MW frequency ranging from 800 to 2000 MHz. METHODS: DNA damage was assessed using the single cell gel electrophoresis assay and aneugenic and clastogenic damage by the in vivo capillary blood micronucleus test (MNT) in a total of 24 mobile phone users. RESULTS: Mean comet tail length (26.76 ± 0.054 mm; 39.75% of cells damaged) in mobile phone users was highly significant from that in the control group. The in vivo capillary blood MNT also revealed highly significant (0.25) frequency of micronucleated (MNd) cells. CONCLUSIONS: These results highlight a correlation between mobile phone use (exposure to RFR) and genetic damage and require interim public health actions in the wake of widespread use of mobile telephony.

BACKGROUND : Cytogenetics study using cultured T-lymphocytes derived from peripheral blood is the easiest way to study human chromosome complement and it is also an excellent method to study chromosomal abnormalities: either structural or numerical. The structural chromosomal abnormalities include translocations, deletions, duplications, ring chromosomes and isochromosomes. AIMS : Cases presenting with multiple congenital anomalies, mental retardation, pregnancy wastage or abnormalities in sexual function are referred to the Division of Human Genetics to rule out chromosomal anomalies. METHODS AND MATERIALS : A total of 70 cases with multiple congenital anomalies, mental retardation, pregnancy wastage or abnormalities in sexual function were studied. About 72 h cultured peripheral lymphocytes subjected to GTG banding were analyzed to look at the chromosome profile. RESULTS : Out of 70 cases of reciprocal translocation, single cell translocations were seen in ten cases (three females; seven males). Looking at the case profile, it was seen that they were referred for mental retardation, bad obstetric history and hypogonadism. It was seen that seven cases (70%) had t(7;14), two (20%) had complex translocations: t(X;9;8) and t(2;10;11), and one (10%) had t(4;21). CONCLUSIONS : Depending on the phenotype, the patients were informed of their abnormality and the need for a look out for the development of any associated problems.

BACKGROUND : Consanguinity is defined as the marriage between close relatives. The deleterious effects associated with consanguinity may be caused by the expression of rare recessive genes inherited from common ancestors. AIMS AND OBJECTIVES : The present study was undertaken to analyze the effect of consanguinity on chromosomal abnormality (CA). METHODS AND MATERIALS : During last 6 years period, a total of 1465 cases with suspected genetic etiology like bad obstetric history, mental retardation, multiple congenital anomalies, Down syndrome, primary amenorrhea and primary infertility was referred to Division of Human Genetics for karyotyping and genetic counseling. The information regarding consanguinity was obtained through pedigree analyzes up to three generations from all the patients. Chi-square test was applied to test the significance. RESULTS : Consanguinity was seen in 427 cases (29.14%), 305 cases were confirmed to have CA, among them 240 (78.7%) had numerical abnormality and 65 (21.3%) had structural abnormality. The presence of consanguinity in CA was seen in 53 cases (17%), including 43 (81.1%) with numerical and 10 (18.9%) with structural abnormality. CONCLUSION : The effect of consanguinity on CA was almost significant ( P < 0.001), whereas the effect was not significant for the type of CA. It may be because of the pooled types of consanguinity as well as the CA. Further information is needed to state categorically that there could be the effect of consanguinity on CA.

Here we present a phenotypic description of a male child with trisomy 8p resulting from a maternal balanced reciprocal translocation. The patient presented with dysmorphic face, aplasia of the corpus callosum, and atrophy of cortex, congenital heart defect and marked hypotonia. The father had a normal karyotype. The mother had an apparently balanced translocation involving chromosomes 8 and 13 [46, XX, t(8;13)(p11.2;p12)]. The karyotype of the child was ascertained as 46, XY, der(13)t(8;13)(p11.2;p12). This is the second reported case of trisomy 8p resulting from a translocation between chromosomes 8 and 13. The chromosomal breakpoints in the two cases differed.