| Autor: |
Shorter, John, Pan, Wenqi, Odet, Fanny, Aylor, David, Kao, Chia-Yu, Fu, Chen-Ping, Greenstein, Seth, Bell, Timothy, Stevans, Alicia, Patel, Sunny, Cates, Sarah, Miller, Darla, McMillian, Leonard, O'Brien, Deborah, Pardo-Manuel de Villena, Fernando |
| Rok vydání: |
2017 |
| Předmět: |
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| DOI: |
10.5281/zenodo.400269 |
| Popis: |
The goal of the Collaborative Cross (CC) project was to generate and distribute hundreds of independent recombinant inbred strains derived from eight inbred parents. Although the project assumed a modest degree of extinction, it soon became clear that extinction was much more prevalent in this multi-parent population. With breeding to homozygosity completed, we can now estimate the extinction rate at remarkable 95% despite considerable efforts to maintain lines with poor reproductive performance. Thus, extinction in the CC represents a unique opportunity to investigate factors that contribute to infertility, often difficult to study because of fitness pressure to purge them from a population. Here we provide the first report of a large and logistically challenging collaboration to systematically phenotype and genotype males from the last generation of CC lines when there were deemed extinct due lack of productivity. We analyzed fertility and a large number of reproductive phenotypes on the last unproductive males from 347 independent CC funnels and performed a trait mapping with the largest number of CC lines to date. Extinction in the CC may be due largely to male infertility, since 47% of males from extinct funnels were infertile. CC extinct fertile and infertile males had similar means and ranges for nearly every reproductive trait measured, suggesting that a single trait is unlikely to explain the observed infertility. We performed QTL mapping across 39 male reproductive traits and identified 9 genomic regions significantly associated with features such as reproductive organ size and sperm motility traits. To demonstrate the effectiveness of trait mapping in the population, we validated a QTL for sperm velocity in an independent population and confirmed the observed allelic effect in multiple generations. Additionally, we identified a large region on chromosome X for genetic infertility driven by the PWK/PhJ haplotype, indicating that genetic incompatibility between founders might also cause CC strain extinction. The results from this study will help us understand genetic factors associated with mammalian infertility, and will also shed light onto reproductive concerns and problems with current breeding of extant CC strains |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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