Identifying the favored mutation in a positive selective sweep.

Most approaches that capture signatures of selective sweeps in population genomics data do not identify the specific mutation favored by selection. We present iSAFE (for "integrated selection of allele favored by evolution"), a method that enables researchers to accurately pinpoint the favored mutation in a large region (∼5 Mbp) by using a statistic derived solely from population genetics signals. iSAFE does not require knowledge of demography, the phenotype under selection, or functional annotations of mutations

Reduction in Renal Function After Renal Arteriography and After Renal Artery Angioplasty

AbstractObjective: to investigate the incidence and risk factors for renal function deterioration after renal angiography and angioplasty or stenting.Methods: a retrospective study of 85 consecutive patients undergoing selective renal artery arteriography (n=53) or renal artery angioplasty % (PTRA) stenting (n=32) for renal artery stenosis. Multivariate logistic regression analysis was used to determine independent predictors of deterioration of renal function, defined as an increase of serum creatinine by at least one third within 24h.Results: deterioration of renal function occurred in 13 patients (15%), [8/53 (15%) after angiography and 5/32 (16%) after PTRA/stenting]. Only pre-existing renal impairment (se-creatinine≥177μmol/l) (Odds ratio: 40; 95% confidence interval 1.2–72, p=0.02) and administered dosage of contrast agent (more than 225ml) (OR 67; 95% CI1 1.8–100, p=0.02) were independently associated with renal function deterioration.Conclusion: transient renal dysfunction after renal artery angiography or PTRA/stenting occurs in about 15% of patients, but persistent renal failure is uncommon. Pre-existing renal impairment and amount of contrast agent are independent risk factors. Endovascular treatment of renal artery stenosis is not associated with a higher risk of renal deterioration compared to selective renal angiography

Diversity of Lactase Persistence Alleles in Ethiopia:Signature of a Soft Selective Sweep

The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (-13910(∗)T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other alleles (-13907(∗)G, rs41525747; -13915(∗)G, rs41380347; -14010(∗)C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP, -14009T>G (ss 820486563), is significantly associated with lactose-digester status, and in vitro functional tests confirm that the -14009(∗)G allele also increases expression of an LCT promoter construct. The derived alleles in the LCT enhancer region are spread through several ethnic groups, and we report a greater genetic diversity in lactose digesters than in nondigesters. By examining flanking markers to control for the effects of mutation and demography, we further describe, from empirical evidence, the signature of a soft selective sweep

Discriminating early-stage diabetic retinopathy with subjective and objective perimetry

Introduction: To prevent progression of early-stage diabetic retinopathy, we need functional tests that can distinguish multiple levels of neural damage before classical vasculopathy. To that end, we compared multifocal pupillographic objective perimetry (mfPOP), and two types of subjective automated perimetry (SAP), in persons with type 2 diabetes (PwT2D) with either no retinopathy (noDR) or mild to-moderate non-proliferative retinopathy (mmDR). Methods: Both eyes were assessed by two mfPOP test methods that present stimuli within either the central ±15° (OFA15) or ±30° (OFA30), each producing per-region sensitivities and response delays. The SAP tests were 24-2 Short Wavelength Automated Perimetry and 24-2 Matrix perimetry. Results: Five of eight mfPOP global indices were significantly different between noDR and mmDR eyes, but none of the equivalent measures differed for SAP. Per-region mfPOP identified significant hypersensitivity and longer delays in the peripheral visual field, verifying earlier findings. Diagnostic power for discrimination of noDR vs. mmDR, and normal controls vs. PwT2D, was much higher for mfPOP than SAP. The mfPOP per-region delays provided the best discrimination. The presence of localized rather than global changes in delay ruled out iris neuropathy as a major factor. Discussion: mfPOP response delays may provide new surrogate endpoints for studies of interventions for early-stage diabetic eye damage.</p