| Title: | The genetic basis of sex-specific fitness variation in humans |
| Lead Institution: | Monash University |
| Principal investigator: | Dr Filip Ruzicka |
Application 52049
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About
Sickle-cell anaemia is an unusually common disease. Why? Because the sickle-cell mutation provides benefits (resistance to malaria in single-copy carriers) that are balanced by its costs (expressing sickle-cell anaemia in double-copy carriers). What if other disease variants, like the sickle-cell mutation, were similarly maintained because they provide benefits that partially offset costs associated with the disease? This project proposes to discover more such variants. It proposes to do so by looking for variants that benefit females and harm males, and variants that benefit males and harm females. Such 'sexually antagonistic' variants are often expected-like the sickle-cell mutation-to be maintained at high frequencies in populations because benefits in one sex are balanced by costs in the other. We propose to find these loci by conducting a 'genome-wide association study' of male and female fitness, and look for variants that differentially affect each sex. By studying these variants in more detail, we will hone in on the traits and diseases that are maintained at high frequency in humans due to opposing fitness effects in each sex. We would also gain further insights into the genetic features that have helped maintain them.2 Publications
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 12585 | An unbiased test reveals no enrichment of sexually antagonistic polymorphisms on the human X chromosome | Filip Ruzicka (+1) | 2022 | Proceedings of the Royal Society B |
| 7046 | Polygenic signals of sex differences in selection in humans from the UK Biobank | Filip Ruzicka (+2) | 2022 | PLOS Biology |
Enabling scientific discoveries that improve human health