Background : The hemoglobinopathies refer to a diverse group of inherited disorders characterized by a reduced synthesis of one or more globin chains (thalassemias) or the synthesis of structurally abnormal hemoglobin (Hb). The thalassemias often coexist with a variety of structural Hb variants giving rise to complex genotypes and an extremely wide spectrum of clinical and hematological phenotypes. Hematological and biochemical investigations and family studies provide essential clues to the different interactions and are fundamental to DNA diagnostics of the Hb disorders. Although DNA diagnostics have made a major impact on our understanding and detection of the hemoglobinopathies, DNA mutation testing should never be considered a shortcut or the test of first choice in the workup of a hemoglobinopathy. Materials and Methods: A careful three-tier approach involving: (1) Full blood count (2) Special hematological tests, followed by (3) DNA mutation analysis, provides the most effective way in which to detect primary gene mutations as well as gene-gene interactions that can influence the overall phenotype. With the exception of a few rare deletions and rearrangements, the molecular lesions causing hemoglobinopathies are all identifiable by PCR-based techniques. Furthermore, each at-risk ethnic group has its own combination of common Hb variants and thalassemia mutations. In Iran, there are many different forms of a and β thalassemia. Increasingly, different Hb variants are being detected and their effects per se or in combination with the thalassemias, provide additional diagnostic challenges. Results:We did step-by-step diagnosis workup in 800 patients with hemoglobinopathies who referred to Research center of Thalassemia and Hemoglobinopathies in Shafa Hospital of Ahwaz Joundishapour University of medical sciences, respectively. We detected 173 patients as iron deficiency anemia (IDA) and 627 individuals as thalassemic patients by use of different indices. We have successfully detected 75% (472/627) of the β -thalassemia mutations by using amplification refractory mutation system (ARMS) technique and 19% (130/627) of the β -thalassemia mutations by using Gap-PCR technique and 6% (25/627) as Hb variants by Hb electrophoresis technique. We did prenatal diagnosis (PND) for 176 couples which had background of thalassemia in first pregnancy. Result of PND diagnosis in the first trimester was 35% (62/176) affected fetus with β -thalassemia major and sickle cell disease that led to termination of the pregnancy. Conclusion:Almost all hemoglobinopathies can be detected with the current PCR-based assays with the exception of a few rare deletions. However, the molecular diagnostic service is still under development to try and meet the demands of the population it serves. In the short term, the current generation of instruments such as the capillary electrophoresis systems, has greatly simplified DNA sequence analysis.

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Identification of genetic variants responsible for complex disorders using association mapping is an active area of research. There are two broad classes of association methodologies: population-based case-control studies and family-based transmission analyses. While case-control analyses are more popular and in general, more powerful than family-based analyses, they suffer from some inherent limitations. Thus, it is of importance, to understand the implications of an association finding obtained from a case-control study design. This article discusses the relative advantages and disadvantages of the two classes of association analyses, particularly in the context of genetic diversity in Indian populations.

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Background : One of the frequent occurrences in chromosome rearrangements is pericentric inversion of the Chromosome 9; inv (9) (p11q12), which is consider to be the variant of normal karyotype. Although it seems not to correlate with abnormal phenotypes, there have been many controversial reports indicating that it may lead to abnormal clinical conditions such as infertility. The incidence is found to be about 1.98% in the general population. Materials and Methods : We investigated the karyotypes of 300 infertile couples (600 individuals) being referred to our infertility clinic using standard GTG banding for karyotype preparation. Results : The chromosomal analysis revealed a total of 15 (2.5%) inversions, among these, 14 male patients were inversion 9 carriers (4.69%) while one female patient was affected (0.33%). The incidence of inversion 9 in male patients is significantly higher than that of normal population and even than that of female patients (P<0.05). Conclusions : This result suggests that inversion 9 may often cause infertility in men due to spermatogenic disturbances, which are arisen by the loops or acentric fragments formed in meiosis.

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Background : The most common type of congenital heart disease is the cardiac septal defects, which has reported to be caused by a missense mutation (G296S) in exon 3 of the GATA4 gene. Aims: The present study was undertaken to find out whether GATA4 gene is the prime cause of the septal defects in Mysore population. Materials and Methods :GATA4 gene analyses were undertaken on 21 confirmed CHD cases by PCR and DNA sequencing. Results and Conclusion :Analysis of this particular mutation in 21 septal defect patients revealed that none of the patients had the mutation, indicating that this mutation is population specific or septal defect in Mysore population is caused due to mutations in other regions of the GATA4 gene.

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We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient.

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Background: The ability to taste phenylthiocarbamide (PTC), a bitter chemical has long been known to be a heritable trait, which is being widely used for both genetic and anthropological studies. The frequency of taster and non-taster allele is found to vary in different populations. Aims and Objective: To investigate the frequency of taster trait in Mysore, South India. Materials and Methods: The present investigation was conducted in Mysore, South India during 2002 - 2003. About 3282 subjects irrespective of age, sex, religion, food habits, socio-economic status were randomly selected from various parts of the city and a total of 180 families, which included Christian (50), Hindu (61) and Muslim (69) were screened from different localities of the city. Harris and Kalmus method was used to assess the PTC taster and nontaster phenotype. Results: It was found that tasters were significantly more frequent than nontasters in all the four categories. The incidence of tasters was more in unbiased category (85%) and less in Muslim category (58%). Investigations on PTC tasting in the families of three different religious groups revealed that the tasters were significantly more frequent than nontasters. It was also found that heterozygous father or mother for the taster genes with nontaster partner had taster and nontaster progenies in the ratio 1.0: 1.54 indicating the deviation in the segregation pattern of test cross. Conclusion: In Mysore, tasters are more frequent than nontasters. Variation in the frequency of nontaster allele in the religious groups could be due to inbreeding.

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Background: The β -thalassemia syndrome is a genetically inherited commonly encountered hematological disorder in the state of Orissa. It causes high degree of morbidity, mortality and fetal wastage in the poor vulnerable people. Aims and Objectives: There is an equal probability (50% chance) in every singleton pregnancy that a carrier parent of β -thalassemia major would either bear normal or carrier offspring, but not two offspring with carrier of β -thalassemia major genotype together. For the first time, a carrier parent of β -thalassemia major gene has born progeny (three daughters and a twin male offspring) with a carrier status of β -thalassemia major in Dudh Kharia tribal family studied from Sundargarh district of Orissa. Materials and Methods: We screened randomly selected population of Dudh Kharia tribe from Sundargarh district of Orissa for hemoglobinopathies to assess the extent of the problem, design possible interventions and provide genetic counseling to them. A family with twin children was identified during screening in Lata Gaon in Bargaon block of Sundargarh district of Orissa for the above-mentioned study. Background information for this family such as name, age, sex, tribe, native place, reproductive history, family pedigree and clinical signs and symptoms were also recorded. Standardized genetic and hematological procedures and techniques were followed for analysis. Results: Laboratory investigations for alkaline electrophoresis of blood lysate on cellulose acetate membrane showed raised hemoglobin A ₂ level in mother (Hb A ₂ = 5.3%), in three daughters (Hb A ₂ =6.5, 5.9, 5.5% in chronological and birth order), in two twin sons (Hb A ₂ =5.9% and 6.0%) and normal (Hb A ₂ = 3.3%) for father. Hence, all the children i.e., three daughters and two twin sons, including the mother were β -thalassemia carriers. Since all the hematological parameters i.e., red cell indices, G-6-PD enzyme activity, ABO and Rhesus blood groups and identical β -thalassemia (trait) genotypes with identical clinical manifestations and hematological profile of the twin sons under similar environmental conditions, hence they were labeled as identical monozygotic twins. Conclusions: It is a rare occasion when a single pregnancy carries either one or two abnormal genotypes at a time in a womb in human beings. Monozygotic twins are genetically alike and provide appraisal of the expression of identical genotype under the different environmental conditions.

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