Understanding inbreeding through the lens of runs-of-homozygosity

Tom Druet

Unit of Animal Genomics, GIGA-R, University of Liège (Belgium)

tom.druet@uliege.be

Link to seminar: https://umontpellier-fr.zoom.us/webinar/register/WN_j9lCmU6zSw-3ZF7XQ6Q_5g

Summary

Inbreeding results from the mating of related individuals, and increases the probability that individuals from the population carry identical-by-descent (IBD) alleles, including deleterious variants associated with recessive genetic defects or that may contribute to inbreeding depression (ID). Within individual genomes, IBD alleles are generally located in extended homozygous-by-descent (HBD) segments that appear as long stretches of homozygous genotypes called runs-of-homozygosity (ROH). We developed a model-based approach to identify such HBD segments based on genotypes, allele frequencies, genotyping errors and the genetic map. The method also works with technologies such as exome sequencing or low-fold sequencing. In the field of animal genetics at large, including wild populations, livestock species, companion animals or species under conservation programs, several applications are nowadays relying on such HBD segments. For instance, since the length of HBD segments is inversely related to the number of generations to the common ancestor, the distribution of ROH in different length-based classes is informative about the past demographic history from a population and its mating structure. In particular, this information can be used to measure the impact of a bottleneck, whereas the absence of recent ROH (e.g., long) might suggest a recovered effective population size (Ne). Furthermore, based on simulations studies and empirical evaluations, we found that the proportion of the genome that is HBD is a reliable estimator of the inbreeding coefficient when Ne is small, and allows consequently to study ID. We are currently applying such approaches in an intensively selected beef cattle population.

Recent publications:

1. Druet T, Gautier M (2022) A hidden Markov model to estimate homozygous-by-descent probabilities associated with nested layers of ancestors. Theor Popul Biol 145:38-51 (2022)

2. Caballero A, Villanueva B, Druet T (2021) On the estimation of inbreeding depression using different measures of inbreeding from molecular markers. Evol Appl. 14(2):416-428.

3. Alemu S, Kadri NK, Harland C, Faux P, Charlier C et al. (2021) An evaluation of inbreeding measures using a whole-genome sequenced cattle pedigree. Heredity 126(3):410-423.

Watch previous seminars on our YouTube channel: https://www.youtube.com/channel/UCrX4IsZ8WIFcDa0ZmC7rcQg