Guy, R. | Search bioRxiv

bioRxiv2019

Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leukocyte antigen locus

Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1,540 controls. Using HLA imputation and linear mixed-models, we find each copy of the HLA-DQA1*01:03 allele associates with a two-fold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P=0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.

genetics↗

bioRxiv2018

MinION re-sequencing of Giardia genomes and de novo assembly of a new Giardia isolate

BackgroundGenomes of the parasite Giardia duodenalis are relatively small for eukaryotic genomes, yet there are only six publicly available. Difficulties in assembling the tetraploid G. duodenalis genome from short read sequencing data likely contribute to this lack of genomic information. We sequenced three isolates of G. duodenalis (AWB, BGS, and beaver) on the Oxford Nanopore Technologies MinION whose long reads have the potential to address genomic areas that are problematic for short reads.\n\nResultsUsing a hybrid approach that combines MinION long reads and Illumina short reads to take advantage of the continuity of the long reads and the accuracy of the short reads we generated reference quality genomes for each isolate. The genomes for two of the isolates were evaluated against the available reference genomes for comparison. The third genome for which there is no previous data was then assembled. The long reads were used to find structural variants in each isolate to examine heterozygosity. Consistent with previous findings based on SNPs, Giardia BGS was found to be considerably more heterozygous than the other isolates that are from Assemblage A. We also find an enrichment of variant-specific surface proteins in some of the structural variant regions.\n\nConclusionsOur results show that the MinION can be used to generate reference quality genomes in Giardia and further be used to identify structural variant regions that are an important source of genetic variation not previously examined in these parasites.

genomics↗