The unique phenomenon of alternative splicing is gathering concern due to its promising therapeutic potential. The human genome sequencing project suggests approximately 20,000-25,000 genes. Among these, about 35-60% of genes generate multiple mRNAs by alternative splicing mechanism and contribute to the diversity of the proteomic world. This 'gene shortfall' has ignited considerable interest in alternative RNA splicing. This process leads to expression of a single gene responsible for the transcription of different mRNA isoforms that might have multiple biological functions. The disruption of splicing pattern can produce aberrant splice variants, which are implicated in more than 50% of genetic disorders including cancer. Altered splice sites in neoplastic cell contribute to the development, progression and/or maintenance of tumorous growth. The repertoire of tumor-specific variant represents a potential marker in pharmacogenomic diagnostic relevance. Alternative splice isoforms have been analyzed serendipitously by qualitative gene profiling with in silico gene prediction software. Computational approach in identifying exonic splicing enhancers in genomic DNA and focus on microarray technology will elucidate differential expression of alternative splice variants. The antisense oligonucleotides modulate alternative splicing and engender the production of therapeutic gene products. Oligonucleotides have the potential to silence the mutations caused by aberrant splicing. The efficacy of the antisense oligonucleotides lies in the chemical configuration, affinity and delivery strategies. Hence the therapeutic potential of antisense oligonucleotides as modulators of aberrant alternative splicing would be a major challenge to the upcoming proteomic era.

AIMS: To detect the frequency and types of both chromosomal abnormalities and Y chromosome microdeletions in infertile men attending to our university intracytoplasmic sperm injection ICSI/IVF centre and fertile control subjects in our patient population. SETTINGS AND DESIGN: A total of 50 infertile men who were referred to IVF center of Meram medical faculty were selected for the molecular azospermia factor (AZF) screening program. MATERIALS AND METHODS: Karyotype analysis and polymerase chain reaction amplification using 15 Y-specific sequence-tagged sites of AZF region were done. RESULTS: The total prevalence of chromosomal abnormalities was found to be 10% (5/50), including 4 patients with numerical and 1 patient with structural abnormalities. Overall, 4 of the 50 patients tested (8%) exhibited deletions of the Y chromosome, 3 of them being azospermic and 1 of them oligospermic men. The frequency of the microdeletions in subgroups with azospermia and oligozoospermia was found to be 10.7% (3/29) and 4.7% (1/21) respectively. Microdeletions of AZFb and AZFc regions were detected in all of the 4 patients. Neither AZFa nor AZFd microdeletions were indicated. CONCLUSIONS: Our findings suggest that one must know whether there is a genetic cause for male infertility before patients can be subjected to ISCI or testicular sperm extraction (TESE)/ISCI treatment.

BACKGROUND: Myopia or nearsightedness is a spherical error of refraction, whereby the images are focused in front of retina. Eye, being an organ rich in activated oxygen species, requires a high level of antioxidants to protect the unsaturated fatty acids. Apolipoprotein E (APOE) is one of the proteins that is produced by Muller cells within the retina and is also endowed with antioxidant properties. Genetic polymorphism of APO E is controlled by three common alleles e3, e2 and e4 and rare e1, e4v at the APOE structural gene locus. Different isoforms of APO E differ in their antioxidant properties, and the e4 allele has lesser ability to combat oxidative stress. AIMS: Myopia being a disease influenced by oxidative stress, the present study was undertaken to find association of myopia with APO E polymorphism. MATERIALS AND METHODS: A total of 187 myopic cases and 192 controls were genotyped for apolipoprotein E polymorphism. RESULTS: In both controls and myopic cases, E3/3 genotype was found to be the most frequent one. There was an increase in E3/4 genotype frequency among male probands, high myopia cases and probands with early age at onset, suggesting that the E3/4 genotype might confer risk for myopia development. CONCLUSION: This association with E3/4 genotype might predispose susceptible individuals to develop high myopia and early onset myopia.

BACKGROUND: More has been written about the epidemiology of breast cancer than any other form of cancer affecting mankind. The specific breast cancer predisposing genes are BRCA1, BRCA2 and p53. BRCA2, the second breast cancer susceptibility gene, was mapped to chromosome 13q12-q13.The human p53 gene, located on the short arm of chromosome 17, is known to be a tumor suppressor gene that can be inactivated by point mutations. AIMS: To determine the fluctuating asymmetry and to predict the occurrence of carcinoma of breast in females. MATERIALS AND METHODS: Rolled finger and palmar prints of 100 female patients of carcinoma of breast were compared with 100 controls. Fluctuating asymmetry measures derived from quantitative parameters (finger ridge counts, a-b ridge counts and palmar angles) were analyzed. RESULTS: Fluctuation asymmetry measures were significantly higher in female patients of carcinoma of breast for the thumb (FA = 2.01), subtotal ridge count (FA = 2.10) and for palmar atd angle (FA = 2.01). CONCLUSION: These findings suggest that digital dermatoglyphics may have a future role in identifying women at increased risk for breast cancer.

BACKGROUND : Mental health is an essential ingredient in the quality of life. Recent studies carried out in countries like Germany, USA, France, England and Belgium have provided evidence for the involvement of L1 (CAM) mutations in various X-linked mental retardation syndromes. L1 CAM is a neural cell adhesion molecule belonging to the superfamily of the immunoglobulins and is critical for proper CNS development in humans. AIM: This study was aimed to screen idiopathic mental retardation cases for L1 CAM mutations. MATERIALS AND METHODS : In this study, we screened 15 cases with mental retardation. Genomic DNA from the patients and control subjects was analyzed by polymerase chain reaction using specific primers. RESULTS : In 2 out of 15 patients, mutation was detected between exon 26 and 27. CONCLUSION : It is worthwhile to screen idiopathic mental retardation cases for L1 CAM mutations to reduce genetic morbidity in the population by offering genetic counseling and prenatal diagnosis.

Background:0 The aboriginal tribes of India constitute an important segment of the society in the world. Though a large number of genetic studies have been carried out in India, the genetic data of the populations in the state of Orissa are very limited, especially pertaining to the indigenous tribal people. Most of the earlier studies were restricted to either a single tribe or a few genetic markers. Data on population structure of tribal communities of Orissa pertaining to common hemolytic disorders and genetic variations are still scanty. AIMS AND OBJECTIVES: In view of the limited data available on the tribes and the huge tribal population, a cross-section of ashram schools was investigated for immuno-hematological disorders in relation to geographical, linguistic and genetic variations. MATERIALS AND METHODS: A cross-section of 15 major scheduled tribes in ashram schools from eight districts of Orissa was randomly studied for five hereditary immuno-hematological markers, namely, the ABO and Rhesus (D) blood groups, sickle cell hemoglobinopathy, β -thalassemia syndrome and G-6-PD deficiency, following the standard hematological procedures and techniques. RESULTS: A preponderance of blood group B over A and low incidence of Rhesus-negative (D-) among Bathudi, Bhuyan, Kissan, Kolha, Kondh, Munda oraon, Paraja, Santal and Saora tribes was observed. The deficiency of G-6-PD enzyme was found to be quite high, varying from 5.1 to 15.9% among these scheduled tribes of Orissa. Both deficient female heterozygotes and homozygotes were encountered. Marked variation was seen in the prevalence of β -thalassemia trait, varying from 0 to 8.5%, in the aboriginal tribes. The frequency of sickle cell disorders was found to vary from 0 to 22.4% among the major tribes, but it was comparatively higher in Paraja (21.5%), Dhelki Kharia (13.7%), Gond (11.9%) and Bhatra (10.5%) tribes. CONCLUSIONS: The study showed genetic heterogeneity and diversity with respect to above immuno-hematological genetic markers and indicated not only the inter-tribal admixture but also diffusion with other racial groups of India. Further, the heterogeneous tribal populations from Orissa were found to harbor almost all major hemoglobinopathies. This is the first comprehensive study of immuno-hematological disorders among the scheduled tribes from the state of Orissa.

Lissencephaly is a clinically and genetically heterogeneous malformation of the brain, leading to a severe disabling condition and seizures. The recent discovery of molecular techniques and identification of lissencephaly genes (LIS 1 and DCX) has allowed etiologic diagnosis of this disorder. We describe a patient with lissencephaly in whom fluorescence in situ hybridization and DCX mutation analysis determined etiologic diagnosis, allowing precise genetic counseling and providing prenatal diagnosis for the family.

Kenny-Caffey syndrome is a rare hereditary skeletal syndrome characterized by dysmorphic features, severe growth retardation, classical radiological changes and hypocalcemia with hypoparathyroidism at an early age. We report an 8-month-old girl child with Kenny-Caffey syndrome who had most of the features of the syndrome. Any child with hypocalcemia who has typical facial features should raise a suspicion of this syndrome.