African ancestry and its correlation to type 2 diabetes in African Americans: a genetic admixture analysis in three U.S. population cohorts

The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES), suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without) from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1) determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2) identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference = 1.6%, P<0.001). The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13-1.55), after adjustment for age, sex, study, body mass index (BMI), and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD = 4.0) and 13q14.3 (Z score = 4.5, P = 6.6 × 10(-6)). In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in diabetes risk.     

Homeotic Arm-to-Leg Transformation Associated with Genomic Rearrangements at the PITX1 Locus

The study of homeotic-transformation mutants in model organisms such as Drosophila revolutionized the field of developmental biology, but how these mutants relate to human developmental defects remains to be elucidated. Here, we show that Liebenberg syndrome, an autosomal-dominant upper-limb malformation, shows features of a homeotic limb transformation in which the arms have acquired morphological characteristics of a leg. Using high-resolution array comparative genomic hybridization and paired-end whole-genome sequencing, we identified two deletions and a translocation 5′ of PITX1. The structural changes are likely to remove active PITX1 forelimb suppressor and/or insulator elements and thereby move active enhancer elements in the vicinity of the PITX1 regulatory landscape. We generated transgenic mice in which PITX1 was misexpressed under the control of a nearby enhancer and were able to recapitulate the Liebenberg phenotype.     

AIDS and associated malignancies

INTRODUCTION It has been over twenty years since the onset of the AIDS epidemic, and in spite of the tremendous progress made towards the understanding of the disease, the virus that causes the disease and the development of highly ef- fective anti-retrov…     

Phosphoglucomutase-1 subtypes in the Albanian ethnic minority of the province of Cosenza (Calabria-Southern Italy): Presence of a new variant

Allele frequencies of the phosphoglucomutase-1 (PGM1), in the Albanian ethnic minority of province of Cosenza (Calabria-Southern Italy) were compared with the corresponding data from neighbouring non-Albanian sample groups. The isoelectrofocusing evaluation in the two populations revealed the presence of a new variant PGM1^*W31 in Albanian sample group. Furthermore, a significant heterogeneity was observed between Albanian allele frequencies and those of the surrounding groups.     

Effects of controlled treatment with trypsin on the functional characteristics of isolated nematocysts of Calliactis parasitica and Aiptasia mutabilis (Cnidaria,Actiniaria)

Glycerol-isolated basitrichs of Calliactis parasitica responsive to thioglycolate had open apical flaps, while unresponsive capsules isolated with Triton X100 or by freezing had closed apical flaps. Limited treatment with trypsin induced the apical flaps to open without causing discharge, suggesting that nematocysts can maintain the resting condition even with open flaps. Trypsin-treated basitrichs acquire a high responsiveness to thioglycolate. Microbasic mastigophores of Aiptasia mutabilis are more responsive to distilled water after controlled trypsin treatment but the apical flaps are unchanged. Ca²⁺ is inhibitory regardless of trypsin treatment. It is proposed that the capsule tip may control the penetration of the discharging agents rather than providing mechanical resistance to inner pressure.