Genetic modifiers of Hb E/beta0 thalassemia identified by a two-stage genome-wide association study.

Background: Patients with Hb E/beta0 thalassemia display remarkable variability in disease severity. To identify genetic modifiers influencing disease severity, we conducted a two-stage genome scan in groups of 207 mild and 305 severe unrelated patients from Thailand with Hb E/beta0 thalassemia and normal alpha-globin genes.

Methods: First, we estimated and compared the allele frequencies of approximately 110,000 gene-based single nucleotide polymorphisms (SNPs) in pooled DNAs from different severity groups.

Genetic analysis of candidate modifier polymorphisms in Hb E-beta 0-thalassemia patients.

Hemoglobin E (Hb E)-beta-thalassemia patients display a range of clinical severities, from nearly asymptomatic to transfusion-dependent thalassemia major. Given this clinical heterogeneity, additional genetic factors modifying disease severity remain to be discovered. Association studies are being conducted to elucidate the role of genetic polymorphisms as disease severity modifiers in Hb E-beta-thalassemia patients.

Resistance to a bacterial toxin is mediated by removal of a conserved glycosylation pathway required for toxin-host interactions.

Crystal (Cry) proteins made by the bacterium Bacillus thuringiensis are pore-forming toxins that specifically target insects and nematodes and are used around the world to kill insect pests. To better understand how pore-forming toxins interact with their host, we have screened for Caenorhabditis elegans mutants that resist Cry protein intoxication. We find that Cry toxin resistance involves the loss of two glycosyltransferase genes, bre-2 and bre-4.