Haemoglobinopathies- thalassaemias and abnormal haemoglobins in Eastern Uttar Pradesh and adjoining districts of neighbouring states

The haemoglobinopathies- thalassaemias and abnormal haemoglobins- constitute a major burden of genetic diseases in India. Our study, based on index cases from 120 families detected between May 1999 and May 2003, highlights the ethnic distribution of haemoglobinopathies in regions in and around Varanasi comprising 8-10 districts of eastern Uttar Pradesh and adjoining districts of Bihar, Jharkhand, Chhattisgarh and Madhya Pradesh. Homozygous and heterozygous β-thalassaemia was the most common (66.9%), with thalassaemic haemoglobinopathies HbE-β-thalassaemia (15.9%) and HbS-β-thalasseamia (7.8%) contributing to almost a quarter of the cases. Along with HbSS disease (4.3%), the results indicate a confluence of β-thalassaemia, HbS and HbE in this region. IVS1-5 nt was the most common mutation in the few carriers analysed for mutation detection. The significance of the study lies in the demonstration of wide prevalence of β-thalassaemia across all castes and communities of this region, with migrant population groups of Sindhis and Punjabis comprising only 5.8% of the index cases. Also, HbE seems to have a much higher presence in this region than so far believed and HbS has a significant presence in general castes as well

Mammalian sex chromosomes. III. Activity of pseudoautosomal steroid sulfatase enzyme during spermatogenesis in Mus musculus

Parallel to the inactivation of the X chromosome in somatic cells of female, the male X in mammals is rendered inactive during spermatogenesis. Pseudoautosomal genes, those present on the X-Y meiotically pairable region of male, escape inactivation in female soma. It is suggested, but not demonstrated, that they may also be refractory to the inactivation signal in male germ cells. We have assayed activity of the enzyme steroid sulfatase, product of a pseudoautosomal gene, in testicular cells of the mouse and shown its presence in premeiotic, meiotic (pachytene), and postmeiotic (spermatid) cell types. It appears that, as in females, pseudoautosomal genes may escape inactivation in male germ cells also

CvSox-4, the lizard homologue of the human SOX4 gene, shows remarkable conservation among the amniotes

SOX family genes share a high sequence similarity with the HMG box region of the human Y chromosomal gene, SRY. We have cloned and sequenced the HMG box motif of a Sox gene of the lizard, Calotes versicolor. A database search for the cloned sequence, CvSox-4, revealed 100% identity with the SOX4 gene of the human and its homologue in a bird. The result strongly suggests that SOX4 evolved prior to the diversification of amniotes and is highly conserved

Developmental methylation of the regulatory region of HoxB5 gene in mouse correlates with its tissue-specific expression

We have studied the dynamics of de novo CpG methylation in the regulatory region of one of the homeobox gene HoxB5 during mouse development by sodium bisulfite sequencing. Methylation pattern was examined at embryonic day 18.5 and adult in kidney and spleen while in the liver the same exercise has been done in 11.5 dpc, 18.5 dpc, 5 dpp and in adult. In the liver at 11.5 dpc, all the 47 contiguous sites (including a CpG island from 2035 to 2330 bp) at 5' regulatory region of HoxB5 were unmethylated. Random methylation commences from 18.5 dpc and continues in 5 dpp and in the adult. In the kidney at 18.5 dpc, 26 CpGs were examined (excluding the CpG island region) and all of them were unmethylated but the fetal spleen had at least a few sites considerably methylated. In the adult there was a low level methylation in the kidney, on the other hand, in the spleen, all the CpGs were methylated except a few sites and certain sites were totally methylated. Thus in the adult, the level of methylation was much higher than in the fetal stage. On the other hand semi-quantitative RT-PCR revealed that the extent of expression of HoxB5 was higher in embryonic stages than in the adult. Thus HoxB5 is a good paradigm to support that the developmental methylation of HoxB5 and its expression pattern show an inverse correlation

Male infertility: Y -chromosome deletion and testicular aetiology in cases of azoo-/oligospermia

1088-1092The spermatogenesis locus azoospermia factor (AZF) in Yq11 has been delineated into three microdeletion intervals designated as AZFa, AZFb and AZFc. AZFc is the most frequently deleted region. We have studied 270 male infertile patients for various genetic disorders associated with infertile phenotype. In this study, we have presented results of our studies on Y -chromosome deletions, chromosomal abnormalities (Klinefelter syndrome) and histology of testis with the objective of seeing whether there were cases of gonosomic mosaicism and a causal correlation between the genetic disorder; and testicular aetiology could be drawn. In all the 13 cases of Y-chromosome microdeletion, AZFc region and DAZ gene were deleted, while no case of AZFa deletion was detected. This result was at variance with other reports from India, where a considerable fraction of cases showed deletion in AZFa region of the Y -chromosome. Both Y -deleted and non-Y –deleted cases revealed heterogeneous testicular phenotype with comparable severity. This disparity among testicular phenotype in cases with known genetic aetiology and even in cases of unknown aetiology can be attributed to different genetic backgrounds and effect of modifiers. Since male infertility is a multifactorial disorder, the contributions of environmental and occupational insults may not be underestimated

A386G polymorphism of the DAZL gene is not associated with idiopathic male infertility in North India

Background: Male infertility is a multifactorial disorder which affects approximately 10% of couples at childbearing age with substantial clinical and social impact. Genetic variation and environmental factors contribute to susceptibility to spermatogenic impairment in humans. The A386G (T54A) polymorphism of the autosomal gene, DAZL, has shown susceptibility to spermatogenic failure in Taiwanese population. However, no such association has been seen in infertile patients from Italy and South India. Aim: This study aims to find out the possible association between A386G (T54A) polymorphism of the autosomal gene, DAZL and idiopathic male infertility in patients from North India. Design: Case-control study. Materials and Methods: The prevalence of A386G (T54A) polymorphism was determined in 165 idiopathic infertile azoo-/oligospermic patients and 200 fertile healthy control men. PCR-RFLP analysis was employed to determine the genotypes. PCR amplicons were subjected to restriction digestion with AluI as this mutation created a restriction site (AGCT), and separated on a 12% polyacrylamide gel. Results: Analysis of 165 idiopathic infertile azoo-/oligospermic and 200 fertile control men revealed only one case of the variant as a heterozygote in the control population. Single Nucleotide Polymorphism (SNP) was absent in the infertile patients. Conclusion: As in the report from Italy and South India, our results illustrate the rarity of this mutation. Apparently, this mutation is of recent origin and/or has poor selective value. Its preponderance in infertile patients from Taiwan (all heterozygotes) suggests a founder effect and also that its low selective value could be due to impaired spermatogenesis

Y-haplotypes and idiopathic male infertility in an Indian population

Infertility being a multifactorial disorder, both genetic and environmental factors contribute to the etiology of infertile phenotype. Chromosomal anomalies and Y-microdeletion are the established genetic risk factors of male infertility. Y-haplotypes has been found as risk factor for male infertility in certain populations, though in certain others no association has been reported, suggesting a population-specific association of these variations with male infertility. In a case-control study, 165 azoo-/oligospermic patients and 200 controls were haplotyped for certain Y-haplogroups for a possible association with idiopathic male infertility in an Indian population. Analysed Y-haplogroups showed no association with infertile phenotype. Thus this genetic factor is not a risk for infertility in the studied Indian population but that does not rule out the possibility of any of them, to be a risk in other populations

Do sister forks of bidirectionally growing replicons proceed at unequal rates?

DNA fibre autoradiography in different tissues of the rodents Bandicota bengalensis and Nesokia indica reveals a high frequency of such bidirectionally replicating replicons whose sister 'hot' tracks are of unequal size. These results suggest intrarepliconic difference in the rates of fork migration in the two directions