MATERIALS AND METHODS: Original research studies associating genetic features and normal tissue complications following radiotherapy were identified from PubMed. The use of dosimetric data was determined by mining the statement of prescription dose, dose fractionation, target volume selection or arrangement and dose distribution. The consideration of the dosimetric data as covariates was based on the statement mentioned in the statistical analysis section. The significance of these covariates was extracted from the results section. Descriptive analyses were performed to determine their completeness and inclusion as covariates.
RESULTS: A total of 174 studies were found to satisfy the inclusion criteria. Studies published ≥2010 showed increased use of dose distribution information (p = 0.07). 33% of studies did not include any dose features in the analysis of gene-toxicity associations. Only 29% included dose distribution features as covariates and reported the results. 59% of studies which included dose distribution features found significant associations to toxicity.
CONCLUSION: A large proportion of studies on the correlation of genetic markers with radiotherapy-related side effects considered no dosimetric parameters. Significance of dose distribution features was found in more than half of the studies including these features, emphasizing their importance. Completeness of radiation-specific clinical data may have increased in recent years which may improve gene-toxicity association studies.
RESULTS: Two individual intraspecific linkage maps consisting of DArTseq markers were constructed in two bambara groundnut (2n = 2x = 22) segregating populations: 1) The genetic map of Population IA was derived from F2lines (n = 263; IITA686 x Ankpa4) and covered 1,395.2 cM across 11 linkage groups; 2) The genetic map of Population TD was derived from F3lines (n = 71; Tiga Nicuru x DipC) and covered 1,376.7 cM across 11 linkage groups. A total of 96 DArTseq markers from an initial pool of 142 pre-selected common markers were used. These were not only polymorphic in both populations but also each marker could be located using the unique sequence tag (at selected stringency) onto the common bean, adzuki bean and mung bean genomes, thus allowing the sequenced genomes to be used as an initial 'pseudo' physical map for bambara groundnut. A good correspondence was observed at the macro synteny level, particularly to the common bean genome. A test using the QTL location of an agronomic trait in one of the bambara groundnut maps allowed the corresponding flanking positions to be identified in common bean, mung bean and adzuki bean, demonstrating the possibility of identifying potential candidate genes underlying traits of interest through the conserved syntenic physical location of QTL in the well annotated genomes of closely related species.
CONCLUSIONS: The approach of adding pre-selected common markers in both populations before genetic map construction has provided a translational framework for potential identification of candidate genes underlying a QTL of trait of interest in bambara groundnut by linking the positions of known genetic effects within the underutilised species to the physical maps of other well-annotated legume species, without the need for an existing whole genome sequence of the study species. Identifying the conserved synteny between underutilised species without complete genome sequences and the genomes of major crops and model species with genetic and trait data is an important step in the translation of resources and information from major crop and model species into the minor crop species. Such minor crops will be required to play an important role in future agriculture under the effects of climate change.
RESULTS: In addition to the Kinabatangan River, a known barrier for dispersal in tree shrews, the heterogeneous landscape along the riverbanks affected the genetic structure in this species. Specifically, while in larger connected forest fragments along the northern riverbank genetic connectivity was relatively undisturbed, patterns of genetic differentiation and the distribution of mitochondrial haplotypes in a local scale indicated reduced migration on the strongly fragmented southern riverside. Especially, oil palm plantations seem to negatively affect dispersal in T. longipes. Clear sex-biased dispersal was not detected based on relatedness, assignment tests, and haplotype diversity.
CONCLUSION: This study revealed the importance of landscape connectivity to maintain migration and gene flow between fragmented populations, and to ensure the long-term persistence of species in anthropogenically disturbed landscapes.
METHODS: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.
RESULTS: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10(-4); OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P = 1.86 × 10(-4); OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r(2) ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.
CONCLUSION: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.
IMPACT: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.