Retinitis Pigmentosa (RP) is a hereditary retinopathy that affects about 2.5 million people worldwide. It is characterized with progressive loss of rods and cones and causes severe visual dysfunction ...and eventual blindness in bilateral eyes. In addition to more than 3000 genetic mutations from about 70 genes, a wide genetic overlap with other types of retinal dystrophies has been reported with RP. This diversity of genetic pathophysiology makes treatment extremely challenging. Although therapeutic attempts have been made using various pharmacologic agents (neurotrophic factors, antioxidants, and anti-apoptotic agents), most are not targeted to the fundamental cause of RP, and their clinical efficacy has not been clearly proven. Current therapies for RP in ongoing or completed clinical trials include gene therapy, cell therapy, and retinal prostheses. Gene therapy, a strategy to correct the genetic defects using viral or non-viral vectors, has the potential to achieve definitive treatment by replacing or silencing a causative gene. Among many clinical trials of gene therapy for hereditary retinal diseases, a phase 3 clinical trial of voretigene neparvovec (AAV2-hRPE65v2, Luxturna) recently showed significant efficacy for RPE65-mediated inherited retinal dystrophy including Leber congenital amaurosis and RP. It is about to be approved as the first ocular gene therapy biologic product. Despite current limitations such as limited target genes and indicated patients, modest efficacy, and the invasive administration method, development in gene editing technology and novel gene delivery carriers make gene therapy a promising therapeutic modality for RP and other hereditary retinal dystrophies in the future.
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•Diverse genetic pathophysiology in retinitis pigmentosa.•Gene therapy as the most promising, molecular therapy for retinitis pigmentosa.•Emerging technologies such as gene editing for retinitis pigmentosa therapy.
Date palm is one of the most economically important woody crops cultivated in the Middle East and North Africa and is a good candidate for improving agricultural yields in arid environments. ...Nonetheless, long generation times (5-8 years) and dioecy (separate male and female trees) have complicated its cultivation and genetic analysis. To address these issues, we assembled a draft genome for a Khalas variety female date palm, the first publicly available resource of its type for a member of the order Arecales. The ∼380 Mb sequence, spanning mainly gene-rich regions, includes >25,000 gene models and is predicted to cover ∼90% of genes and ∼60% of the genome. Sequencing of eight other cultivars, including females of the Deglet Noor and Medjool varieties and their backcrossed males, identified >3.5 million polymorphic sites, including >10,000 genic copy number variations. A small subset of these polymorphisms can distinguish multiple varieties. We identified a region of the genome linked to gender and found evidence that date palm employs an XY system of gender inheritance.
Diabetes and cancer are two heterogenous diseases which are rapidly increasing in prevalence globally. A link between these two non-communicable diseases was first identified over 100 years ago; ...however, recent epidemiological studies and advances in genomic research have provided greater insight into the association between diabetes and cancer. Epidemiological studies have suggested that individuals with diabetes have an increased risk of several types of cancer (including liver, pancreas, colorectal, breast, and endometrial) and an increased risk of cancer mortality. However, this increased risk is not observed in all cancers, for example, there is a reduced risk of prostate cancer in individuals with diabetes. It has also been observed that cancer patients have an increased risk of developing diabetes, highlighting that the relationship between these diseases is not straightforward. Evidence of a shared genetic aetiology along with numerous lifestyle and clinical factors have made it challenging to establish if the relationship between the two diseases is causal or a result of confounding factors. This review takes a pan-cancer approach to highlight the complexities of the interactions between type 2 diabetes and cancer development, indicating where advances in genomic research have enabled a greater insight into these two diseases.
Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide with more than 1.85 million cases and 850 000 deaths annually. Of new colorectal cancer diagnoses, 20% of patients ...have metastatic disease at presentation and another 25% who present with localized disease will later develop metastases.
Colorectal cancer is the third most common cause of cancer mortality for men and women in the United States, with 53 200 deaths projected in 2020. Among people diagnosed with metastatic colorectal cancer, approximately 70% to 75% of patients survive beyond 1 year, 30% to 35% beyond 3 years, and fewer than 20% beyond 5 years from diagnosis. The primary treatment for unresectable metastatic CRC is systemic therapy (cytotoxic chemotherapy, biologic therapy such as antibodies to cellular growth factors, immunotherapy, and their combinations.) Clinical trials completed in the past 5 years have demonstrated that tailoring treatment to the molecular and pathologic features of the tumor improves overall survival. Genomic profiling to detect somatic variants is important because it identifies the treatments that may be effective. For the 50% of patients with metastatic CRC with KRAS/NRAS/BRAF wild-type tumors, cetuximab and panitumumab (monoclonal antibodies to the epithelial growth factor receptor EGFR), in combination with chemotherapy, can extend median survival by 2 to 4 months compared with chemotherapy alone. However, for the 35% to 40% of patients with KRAS or NRAS sequence variations (formerly termed mutations), effective targeted therapies are not yet available. For the 5% to 10% with BRAF V600E sequence variations, targeted combination therapy with BRAF and EGFR inhibitors extended overall survival to 9.3 months, compared to 5.9 months for those receiving standard chemotherapy. For the 5% with microsatellite instability (the presence of numerous insertions or deletions at repetitive DNA units) or mismatch repair deficiency, immunotherapy may be used in the first or subsequent line and has improved treatment outcomes with a median overall survival of 31.4 months in previously treated patients.
Advances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets. Although cures remain uncommon, more patients can anticipate extended survival. Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.
Animals transmit not only DNA but also other molecules, such as RNA, proteins and metabolites, to their progeny via gametes. It is currently unclear to what extent these molecules convey information ...between generations and whether this information changes according to their physiological state and environment. Here, we review recent work on the molecular mechanisms by which 'epigenetic' information is transmitted between generations over different timescales, and the importance of this information for development and physiology.
Brazil is the world’s largest producer of sugarcane and one of the leading suppliers of sugar and ethanol worldwide. In the 2019–2020 crop season, the country produced 642.7 million tons of sugarcane ...in a harvest area of 8.44 million hectares. Historically, sugarcane breeding has contributed continuously to increasing yields by regularly releasing superior cultivars for use by the Brazilian industry. In the last 40 years, an average annual increase of 155.7 kg ha
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of sugar yield has been reported, about half of which may be attributed to breeding programs. However, due to the size of the country, the intensive expansion of the crop to low-fertility soils in the last few years, especially in degraded pasture areas, and the widespread adoption of mechanization, new challenges have been imposed on national breeding programs. This review covers the current situation with sugarcane breeding in Brazil and the main advances that have allowed the country to maintain world leadership in developing the industry. Additionally, the history of sugarcane breeding, current national breeding institutions, germplasm development, key breeding objectives, selection stages and methodologies are summarized. An overview is also presented of biotechnological approaches which have become key tools for improving Brazilian traditional breeding programs. The adoption of strategies to increase Brazilian sugarcane yield, aiming to consolidate crop production in a food and energy matrix, is also discussed.
The analysis of the first plant genomes provided unexpected evidence for genome duplication events in species that had previously been considered as true diploids on the basis of their genetics. ...These polyploidization events may have had important consequences in plant evolution, in particular for species radiation and adaptation and for the modulation of functional capacities. Here we report a high-quality draft of the genome sequence of grapevine (Vitis vinifera) obtained from a highly homozygous genotype. The draft sequence of the grapevine genome is the fourth one produced so far for flowering plants, the second for a woody species and the first for a fruit crop (cultivated for both fruit and beverage). Grapevine was selected because of its important place in the cultural heritage of humanity beginning during the Neolithic period. Several large expansions of gene families with roles in aromatic features are observed. The grapevine genome has not undergone recent genome duplication, thus enabling the discovery of ancestral traits and features of the genetic organization of flowering plants. This analysis reveals the contribution of three ancestral genomes to the grapevine haploid content. This ancestral arrangement is common to many dicotyledonous plants but is absent from the genome of rice, which is a monocotyledon. Furthermore, we explain the chronology of previously described whole-genome duplication events in the evolution of flowering plants.
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