PyPop update--a software pipeline for large-scale multilocus population genomics.

Population genetic statistics from multilocus genotype data inform our understanding of the patterns of genetic variation and their implications for evolutionary studies, generally, and human disease studies in particular. In any given population one can estimate haplotype frequencies, identify deviation from Hardy-Weinberg equilibrium, test for balancing or directional selection, and investigate patterns of linkage disequilibrium. Existing software packages are oriented primarily toward the computation of such statistics on a population-by-population basis, not on comparisons among populations and across different statistics. We developed PyPop (Python for Population Genomics) to facilitate the analyses of population genetic statistics across populations and the relationships among different statistics within and across populations. PyPop is an open-source framework for performing large-scale population genetic analyses on multilocus genotype data. It computes the statistics described above, among others. PyPop deploys a standard Extensible Markup Language (XML) output format and can integrate the results of multiple analyses on various populations that were performed at different times into a common output format that can be read into a spreadsheet. The XML output format allows PyPop to be embedded as part of a larger analysis pipeline. Originally developed to analyze the highly polymorphic genetic data of the human leukocyte antigen region of the human genome, PyPop has applicability to any kind of multilocus genetic data. It is the primary analysis platform for analyzing data collected for the Anthropological component of the 13th and 14th International Histocompatibility Workshops. PyPop has also been successfully used in studies by our group, with collaborators, and in publications by several independent research teams.

The changing prevalence of drug-resistant Escherichia coli clonal groups in a community: evidence for community outbreaks of urinary tract infections.

A multidrug-resistant clonal group (CgA) of Escherichia coli was shown to cause half of all trimethoprim-sulphamethoxazole (TMP-SMZ)-resistant urinary tract infections (UTIs) in a college community between October 1999 and January 2000. This second study was conducted to determine the fate of CgA. Urine E. coli isolates from women with UTI, collected between October 2000 and January 2001, were tested for antibiotic susceptibility, O serogroup, ERIC2 PCR and DNA macrorestriction patterns using pulsed-field gel electrophoresis. The proportion of UTIs caused by CgA declined by 38% (P<0.001) but the prevalence of resistance to TMP-SMZ did not change. Six additional clonal groups were identified and these were responsible for 32% of TMP-SMZ-resistant UTIs. The temporal decline in the proportion of UTIs caused by CgA provides evidence that CgA caused a community outbreak of UTI. The fluctuation and occurrence of other E. coli clonal groups in this community suggest that a proportion of community-acquired UTIs may be caused by E. coli disseminated from one or more point sources.

Genomic characterization of equine interleukin-4 receptor alpha-chain (IL4R).

Three overlapping fragments of the equine interleukin-4 receptor alpha chain gene (IL4R) were cloned and sequenced. The resulting 3553 bp cDNA sequence exhibited homology to human, murine and bovine IL4R. The equine IL4R exhibits many conserved features when compared to other species, including intron-exon boundary positions and amino acid sequence motifs characteristic of type I cytokine receptors. The IL4R gene was localized to horse chromosome ECA13 by synteny mapping on a somatic cell hybrid panel. Evidence for an alternative splice variant of IL4R was found in the genomic sequence and subsequently verified using RT-PCR on equine monocyte RNA. A polymorphism screen of the largest exon, homologous to exon 12 of the human IL4R gene, was performed using DNA from 60 horses of various breeds which yielded 11 coding-region single nucleotide polymorphisms (SNPs), 7 synonymous and 4 non-synonymous. Three of the four non-synonymous SNPs occur at high frequencies and are found very near a conserved tyrosine residue.