Histo-blood group gene polymorphisms as potential genetic modifiers of infection and cystic fibrosis lung disease severity

Background: The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH) differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF. Methods and Principal Findings: Clinical information and DNA was collected on >800 patients with the ΔF508/ΔF508 genotype. Patients in the most severe and mildest quartiles for lung phenotype were enrolled. Blood samples underwent lymphocyte transformation and DNA extraction using standard methods. PCR and sequencing were performed using standard techniques to identify the 9 SNPs required to determine ABO blood type, and to identify the four SNPs that account for 90-95% of Lewis status in Caucasians. Allele identification of the one nonsynonymous SNP in FUT2 that accounts for >95% of the incidence of nonsecretor phenotype in Caucasians was completed using an ABI Taqman assay. The overall prevalence of ABO types, and of FUT2 (secretor) and FUT 3 (Lewis) alleles was consistent with that found in the Caucasian population. There was no difference in distribution of ABH type in the severe versus mild patients, or the age of onset of Pseudomonas aeruginosa infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type. Conclusions and Significance: Polymorphisms in the genes encoding ABO blood type, secretor or Lewis genotypes were not shown to associate with severity of CF lung disease, or age of onset of P. aeruginosa infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the ΔF508 mutation

Novel variation at chr11p13 associated with cystic fibrosis lung disease severity

Published genome-wide association studies (GWASs) identified an intergenic region with regulatory features on chr11p13 associated with cystic fibrosis (CF) lung disease severity. Targeted resequencing in n=377, followed by imputation to n=6,365 CF subjects, was used to identify unrecognized genetic variants (including indels and microsatellite repeats) associated with phenotype. Highly significant associations were in strong linkage disequilibrium and were seen only in Phe508del homozygous CF subjects, indicating a CFTR genotype-specific mechanism

Researcher as Artist/Artist as Researcher

This is a postmodern article that is nontraditional in its form, content, and mode of representation. Upon recognizing that we share interests and common experiences as artists, we decided to collect life history information from each other about our artistic experiences. Thus we have become, simultaneously, "the researched" and "the re searcher." In these conversations, we explore the ways in which we were each guided by our past, very strong aesthetic and artistic experiences. We also include the voices of other researchers and artists in our conversations as we explore the influences of art in the formation of our worldviews.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68774/2/10.1177_107780049500100107.pd

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Measurement of the CP-Violating Asymmetry Amplitude sin2β\beta

We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.033 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.017 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe