Removal of alleles by genome editing (RAGE) against deleterious load

Abstract Background In this paper, we simulate deleterious load in an animal breeding program, and compare the efficiency of genome editing and selection for decreasing it. Deleterious variants can be identified by bioinformatics screening methods that use sequence conservation and biological prior information about protein function. However, once deleterious variants have been identified, how can they be used in breeding? Results We simulated a closed animal breeding population that is subject to both natural selection against deleterious load and artificial selection for a quantitative trait representing the breeding goal. Deleterious load was polygenic and was due to either codominant or recessive variants. We compared strategies for removal of deleterious alleles by genome editing (RAGE) to selection against carriers. When deleterious variants were codominant, the best strategy for prioritizing variants was to prioritize low-frequency variants. When deleterious variants were recessive, the best strategy was to prioritize variants with an intermediate frequency. Selection against carriers was inefficient when variants were codominant, but comparable to editing one variant per sire when variants were recessive. Conclusions Genome editing of deleterious alleles reduces deleterious load, but requires the simultaneous editing of multiple deleterious variants in the same sire to be effective when deleterious variants are recessive. In the short term, selection against carriers is a possible alternative to genome editing when variants are recessive. Our results suggest that, in the future, there is the potential to use RAGE against deleterious load in animal breeding

Analysis of a large dataset reveals haplotypes carrying putatively recessive lethal and semi-lethal alleles with pleiotropic effects on economically important traits in beef cattle

Additional file 6: Table S5. Protein coding genes between 51,611,400 and 53,234,159 bp on bovine chromosome 16 for the SI16H5 haplotype; the genes showing prenatal or perinatal lethality in mice are in bold. The data provided represent protein coding genes located on the haplotype (SI16H5) that carries putatively recessive lethal allele

Prognostic value of staging laparotomy in supradiaphragmatic clinical stage I and II Hodgkin\u27s disease

In the period 1974-1989, 219 patients with supradiaphragmatic clinical stage I and II Hodgkin\u27s disease were treated at the Institute of Oncology in Ljubljanaof these 95 (43%) patients underwent staging laparotomy. Of laparotomized patients, those with pathological stage III-IV, and of non-laparotomized, those with unfavorable prognostic factors (B-symptoms, bulky mediastinum) received chemotherapy: the remaining patients were treated by irradiation. No statistically significant difference in the survival and disease-free survival between laparotomized and nonlaparotomized patients could be found