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Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome-wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, in the Amhara, SNP rs10803083 is associated with hemoglobin levels at genome-wide levels of significance. No significant genotype association was observed for oxygen saturation levels in either ethnic group. Approaches based on allele frequency divergence did not detect outliers in candidate hypoxia genes, but the most differentiated variants between high- and lowlanders have a clear role in pathogen defense. Interestingly, a significant excess of allele frequency divergence was consistently detected for genes involved in cell cycle control and DNA damage and repair, thus pointing to new pathways for high altitude adaptations. Finally, a comparison of CpG methylation levels between high- and lowlanders found several significant signals at individual genes in the Oromo. [ABSTRACT FROM AUTHOR]

Inherited retinal diseases (IRDs) are a heterogeneous group of conditions that include retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EO[S]RD), which differ in severity and age of onset. IRDs are caused by mutations in >250 genes. Variants in the RPE65 gene account for 0.6–6% of RP and 3–16% of LCA/EORD cases. Voretigene neparvovec is a gene therapy approved for the treatment of patients with an autosomal recessive retinal dystrophy due to confirmed biallelic RPE65 variants (RPE65-IRDs). Therefore, the accurate molecular diagnosis of RPE65-IRDs is crucial to identify 'actionable' genotypes—i.e., genotypes that may benefit from the treatment—and is an integral part of patient management. To date, hundreds of RPE65 variants have been identified, some of which are classified as pathogenic or likely pathogenic, while the significance of others is yet to be established. In this review, we provide an overview of the genetic diagnostic workup needed to select patients that could be eligible for voretigene neparvovec treatment. Careful clinical characterization of patients by multidisciplinary teams of experts, combined with the availability of next-generation sequencing approaches, can accelerate patients' access to available therapeutic options. [ABSTRACT FROM AUTHOR]

The article examines the plasma hepcidin of Ethiopian highlanders with stead-state hypoxia. It states that hepcidin can impede iron absorption and suppressed when erythropoietic iron increases. It notes that concentrations of plasma hepcidin drop when iron demands increased for erythropoiesis and hemoglobin synthesis. The authors conducted experiments to people of Amhara and Oromo in Ethiopia who have been living for more than 500 years.

Data on the distribution of HBV-DNA and other serological markers of hepatitis B virus infection in a population of asymptomatic carriers in Ethiopia are reported. As compared to data from other countries of similar or lower levels of endemicity, it has been found that HBV-DNA prevalence and its correlation with HBeAg/anti-HBe status is similar to that of northern Europe. HBV-DNA is present in 84% of HBe Ag-positive sera but in only 4% of anti-HBe-positive sera, where the lowest concentration of DNA (less than 5 pgr/20 microliters) was found. The trend of increasing prevalence of serological markers with age seems to indicate a considerable horizontal transmission still present in this age range (18-30). In keeping with data of other authors a 3% of HBV-DNA positivity in anti HBc only positive sera was found. No regional or ethnical differences of HBV-DNA positive sera across the country were observed. There is also no evidence of any correlation between HBV-DNA prevalence and HBsAg subtypes ad and ay.

A nationwide seroepidemiological study of hepatitis B markers prevalence was conducted in Ethiopia on 5,270 young males from all regions of the country. Overall prevalence rates were 10.8% for HBsAg and 73.3% for "at least one marker positive"; a remarkable geographical and ethnic variability of marker prevalence was observed, reflecting the wide differences existing in Ethiopia in sociocultural environment and activities such as tribal practices and traditional surgery. Sexual practices and medical exposure also play some role as determinants of hepatitis B marker prevalence in Ethiopia. General preventive measures, with particular reference to health education, by affecting incriminating habits and practices could have some impact on infection rates in Ethiopia, in the absence of a vaccination strategy presently unrealistic in this region of the world.