Signaling by the second messenger inositol 1,4,5-trisphosphate is thought to affect several developmental and physiological processes. Mutants in the inositol 1,4,5-trisphosphate receptor (itpr) gene of Drosophila exhibit delays in molting while stronger alleles are also larval lethal. In a freshly generated set of EMS alleles for the itpr locus we have sequenced and identified single point mutations in seven mutant chromosomes. The predicted allelic strength of these mutants matches the observed levels of lethality. They range from weak hypomorphs to complete nulls. Interestingly, lethality in three heteroallelic combinations has a component of cold sensitivity. The temporal focus of cold sensitivity lies in the larval stages, predominantly at second instar. Coupled with our earlier observation that an itpr homozygous null allele dies at the second instar stage, it appears that there is a critical period for itpr gene function in second instar larvae. Here we show that the focus of this critical function lies in aminergic cells by rescue with UAS-itpr and DdC GAL4. However, this function does not require synaptic activity, suggesting that InsP 3 -mediated Ca 2ϩ release regulates the neurohormonal action of serotonin.

We report here the haplotypes of 10 MstII-defined SS patients and a S/beta o thalassemia from the Central African Republic, exhibiting 7 different atypical haplotypes that are different from the typical Bantu haplotype that characterize over 93% of the beta s bearing chromosomes in that region of Africa. Of the seven atypical haplotypes, six can be easily interpreted as the result of recombination around the "hot spot" 5' of the beta gene, between a typical Bantu haplotype and other haplotypes available in the normal population. Except for one case that requires further study, this result demonstrates that the main mutational event leading to sickle hemoglobin in Bantu-speaking Africa was the mutation of the beta gene in a Bantu haplotype background.