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Background Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab-Indian (AI) haplotype and Benin haplotype of sickle cell anemia. Methods and Results Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~20%), African Americans (HbF ~7%), and Saudi Arabs from the Southwestern Province (HbF ~12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts was approximately 6%. Conclusions Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF.

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Following the recent method due to Hill, Shafi, and Wetterich, we investigate the impact of higher-dimensional operators (d ? 5) induced by gravity and compactification of extra dimensions, on the minimal SU(5) grand unified theory. Modifications caused by the d = 5 operator alone seem to be ruled out, even if the compactification scale Mc is as low as 10" GeV, as they require sin2ew 5 0.203 in conflict with the present world average. The addltion of a six-dimensional operator is found to allow only high unification masses Mu -(O. 1-1 )Mc, with Mc= 10"-10'~ GeV and sin *Ow 20.22-0.24, The grand-unification coupling constant is also found to be significantly smaller.

We studied the roles of vitamin D and its receptor, VDR, in the progression of leprosy. The majority of individuals with leprosy from Kolkata, India, with a type 1 or type 2 reaction have low levels of vitamin D3 in serum samples. Interestingly, individuals with a type 2 reaction associated with neuritis/erythema nodosum leprosum had very low VDR mRNA expression levels, ranging from 5% to 10%, compared to that of healthy control subjects; these patients also had a high bacilli index, ranging from 3+ to 5+. This is the first report to indicate that VDR expression levels may determine the complexity and severity of the progression of leprosy.

In India, the Chhattisgarh State screening programme for sickle haemoglobin focuses on children aged 3-15 years and has screened over 1,050,440 subjects over the last 6 years. Commencing in the District around the capital Raipur, this programme has now completed screening in 7 of the 27 Districts of Chhattisgarh State. Screening is initially performed by solubility tests on fingerprick samples in the field and those with positive tests have venipunctures for haemoglobin electrophoresis. The frequency of the sickle cell trait was 9.64 % and of the SS phenotype 0.29 % with only two Districts in Hardy-Weinberg equilibrium, most Districts showing an excess of the SS 'phenotype' most readily explained by symptomatic selection. The estimated costs were US$0.28 (solubility tests alone) and US$0.60 (haemoglobin electrophoresis). Of the social groupings commonly used in India, the OBC's (other backward classes) had the highest frequencies of the sickle cell gene mutations, followed by the Scheduled Tribes and the Scheduled Castes. The objectives of the programme were the detection of sickle cell disease for prospective clinical management and of the sickle cell trait for purposes of genetic counselling. The former objective is being met for diagnosis although the success of referral to clinic services requires audit. The objective of genetic counselling is compromised by the failure of the screening test to detect other genes of potential clinical significance such as HbD Punjab and the beta thalassaemia trait. Despite these exceptions, the detection of HbS appears relatively robust and could be another condition factored into the traditions of partner selection amongst the underprivileged communities of this state. Overall, the Chhattisgarh programme seeks to address the daunting challenges of large populations carrying the sickle cell gene and maybe a useful model for elsewhere.

Early detection of sickle cell disease (SS) done by neonatal screening will help in early prevention and management of complications in postnatal period.

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