Population genetic diversity of two pathogens and the role of balancing selection in HLA immunogenetics

Molecular epidemiology of rotavirus in Ecuador. The results of five years of rotavirus surveillance among rural populations in northern, coastal Ecuador are detailed. During this period, 839 diarrheal samples were collected from a study population of more than 5000 persons. 2308 stool samples from healthy controls were also collected. Rotavirus antigen was detected in 22% of the cases and 3% of the controls. Rotavirus prevalence did not vary greatly throughout the year, but was slightly elevated from June through September. Prevalence of asymptomatic rotavirus was remarkably constant across all age groups, although we detected a slightly increased rate among young women, suggestive of child-care associated transmission. Fully 61% of the rotavirus positive stool samples could not be adequately typed for VP4 or VP7 genotype. The possibility of sample degradation was considered but discounted after an experimental examination of rotavirus stability and the visualization by electron microscopy of rotavirus-like particles in several untypeable samples. Finally, a novel strain, which had been initially untypeable, was characterized for the VP4, VP6, and VP7 gene segments. Sequence analysis of the VP4 gene showed that primer sequence mismatch was the cause of genotyping failure. The diversity of rotavirus genotypes has important implications for current and future genotyping schemes and the vaccine programs that they inform.;Balancing selection and heterogeneity across the classical HLA loci: a meta-analytic review of 497 population studies. This paper presents a meta-analysis of high-resolution human leukocyte antigen (HLA) allele frequency data describing 497 population samples. Most of the datasets were compiled from studies published in eight journals from 1990 to 2007; additional datasets came from the International Histocompatibility Workshops and from the AlleleFrequencies.net database. In all, these data represent approximately 66,800 individuals from throughout the world, providing an opportunity to observe trends that may not have been evident at the time the data were originally analyzed, especially with regard to the relative importance of balancing selection among the HLA loci. Population genetic measures of allele frequency distributions were summarized across populations by locus and geographic region. A role for balancing selection maintaining much of HLA variation was confirmed. Further, the breadth of this meta-analysis allowed the ranking of the HLA loci, with DQA1 and HLA-C showing strongest balancing selection and DPB1 being compatible with neutrality. Comparisons of the allelic spectra reported by studies since 1990 suggest that most of the HLA alleles identified since 2000 are very low frequency alleles. The literature-based allele-count data, as well as maps summarizing the geographic distributions for each allele, are available online.;Origin of class 1 and 2 integrons and gene cassettes in a population-based sample of uropathogenic Escherichia coli. The prevalence of urinary tract infections (UTI) caused by trimethoprim-sulfamethoxazole (TMP-SMX)-resistant Escherichia coli is increasing and varies geographically in the United States. Recent community-based UTI studies have demonstrated geographic clustering of an Escherichia coli clonal group, suggesting occurrence of a community outbreak of UTI. A large proportion of this clonal group (designated CgA) isolated from women in a California college community was found to be resistant to TMP-SMX. We wished to determine if the acquisition of TMP-SMX resistance by CgA occurred before or after the CgA strains were introduced into this community. Between October 1999 and January 2000, and between October 2000 and January 2001, 482 E. coli isolates were consecutively collected from the urine sample of women with UTI at a student health clinic, and analyzed for determinants of TMP-SMX resistance. In particular, the distribution of integrons harboring resistance cassettes for TMP-SMX (dfr) was examined. Among 95 TMP-SMX-resistant isolates, 68 and 27 isolates carried class 1 and class 2 integrons, respectively. A class 1 integron was found in 25 (93%) of 27 TMP-SMX-resistant CgA isolates but in only 43 (63%) of 68 TMPSMX-resistant non-CgA isolates (p<0.001), and in none of 44 TMP-SMX-susceptible E. coli isolates (p<0.0001). CgA strains carried only a single arrangement of class 1 gene cassettes (dfrA17-aadA5), while the non-clonal group strains carried 9 different cassette arrangements. These results support the idea that CgA strains acquired their resistance at a common site prior to their spread to the college community.