Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility.

ABSTRACT: As the central component of the human endotoxin sensor, Toll-like receptor 4 (TLR4) functions in the early detection and response to Gram-negative infection. We therefore examined a large collection of patients with meningococcal sepsis, comparing the frequency of rare TLR4 coding changes to those in an ethnically matched control population. TLR2 sequences were also acquired and compared. Total nucleotide variation at TLR4 and TLR2 loci was assayed by using a novel computational method. A total of 3.01 megabases of coding sequence was captured at these loci from white subjects with or without meningococcal disease. Authentic mutations were found and high-quality, bidirectional coverage was measured across the coding region by using mutationseeker, a program specifically designed to assay l

SUBMITTER: Smirnova I 

PROVIDER: S-EPMC156328 | biostudies-literature | 2003 May

REPOSITORIES: biostudies-literature