Limited haplotype diversity underlies polygenic trait architecture across 70 years of wheat breeding

Background Selection has dramatically shaped genetic and phenotypic variation in bread wheat. We can assess the genomic basis of historical phenotypic changes, and the potential for future improvement, using experimental populations that attempt to undo selection through the randomizing effects of recombination. Results We bred the NIAB Diverse MAGIC multi-parent population comprising over 500 recombinant inbred lines, descended from sixteen historical UK bread wheat varieties released between 1935 and 2004. We sequence the founders’ genes and promoters by capture, and the MAGIC population by low-coverage whole-genome sequencing. We impute 1.1 M high-quality SNPs that are over 99% concordant with array genotypes. Imputation accuracy only marginally improves when including the founders’ genomes as a haplotype reference panel. Despite capturing 73% of global wheat genetic polymorphism, 83% of genes cluster into no more than three haplotypes. We phenotype 47 agronomic traits over 2 years and map 136 genome-wide significant associations, concentrated at 42 genetic loci with large and often pleiotropic effects. Around half of these overlap known quantitative trait loci. Most traits exhibit extensive polygenicity, as revealed by multi-locus shrinkage modelling. Conclusions Our results are consistent with a gene pool of low haplotypic diversity, containing few novel loci of large effect. Most past, and projected future, phenotypic changes arising from existing variation involve fine-scale shuffling of a few haplotypes to recombine dozens of polygenic alleles of small effect. Moreover, extensive pleiotropy means selection on one trait will have unintended consequences, exemplified by the negative trade-off between yield and protein content, unless selection and recombination can break unfavorable trait-trait associations

Challenges in the diagnosis and management of musculoskeletal tumours in Nigeria

The management of musculoskeletal tumours is important because of the high mortality rates associated with the available treatment modalities. A 5-year prospective study of bone and soft-tissue tumours is presented, along with the difficulties encountered in diagnosis and treatment. There were 71 patients (male:female ratio of 1.7:1, age range 5–85 years, mean age 32 years) with an average duration of 24.7 weeks (range 1 day to 34 years) before presentation. No patient had computed tomography (CT) scanning or magnetic resonance imaging (MRI) due to financial constraints, 95% had biopsies and X-rays, 15% could afford chemotherapy/ror chemotherapy is a sad consequence. 50% agreed to amputation. In the soft-tissue sarcoma group, only one of three patients could pay for limb-sparing surgery. In the benign group, 65% had limb-sparing surgeries and 15% had amputation. Fifty percent (50%) of patients were lost to follow up within 3 months and 39% of the malignant group died within the same period. Musculoskeletal tumours are a reality in our environment and a significant portion of our population have financial limitations. Ignorance and cultural beliefs promote late presentation to our hospitals, which are poorly equipped to give optimal care, despite the presence of trained personnel

Multi-parent populations in crops: a toolbox integrating genomics and genetic mapping with breeding

Crop populations derived from experimental crosses enable the genetic dissection of complex traits and support modern plant breeding. Among these, multi-parent populations now play a central role. By mixing and recombining the genomes of multiple founders, multi-parent populations combine many commonly sought beneficial properties of genetic mapping populations. For example, they have high power and resolution for mapping quantitative trait loci, high genetic diversity and minimal population structure. Many multi-parent populations have been constructed in crop species, and their inbred germplasm and associated phenotypic and genotypic data serve as enduring resources. Their utility has grown from being a tool for mapping quantitative trait loci to a means of providing germplasm for breeding programmes. Genomics approaches, including de novo genome assemblies and gene annotations for the population founders, have allowed the imputation of rich sequence information into the descendent population, expanding the breadth of research and breeding applications of multi-parent populations. Here, we report recent successes from crop multi-parent populations in crops. We also propose an ideal genotypic, phenotypic and germplasm 'package' that multi-parent populations should feature to optimise their use as powerful community resources for crop research, development and breeding