Runs of homozygosity and analysis of inbreeding depression

Authors: SUMREDDEE, PATTARAPOL - University Of Georgia; Toghiani, Sajjad; Hay, El Hamidi; Roberts, Andrew; AGGREY, SAMUEL - University Of Georgia; REKAYA, ROMDHANE - University Of Georgia

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/7/2020
Publication Date: 11/12/2020
Citation: Sumreddee, P., Toghiani, S., Hay, E.A., Roberts, A.J., Aggrey, S., Rekaya, R. 2020. Runs of homozygosity and analysis of inbreeding depression. Journal of Animal Science. 98(12):1-11. https://doi.org/10.1093/jas/skaa361.
DOI: https://doi.org/10.1093/jas/skaa361

Interpretive Summary: Inbreeding leads to detrimental effects on growth and fitness related traits in beef cattle. The availability of genomic information provides a unique opportunity to dissect the mechanism of inbreeding and its effects on economically important traits. The objectives of this study are: 1) develop an algorithm to detect inbred regions in the genome of Line 1 Hereford animals and 2) assess the extent of inbreeding depression. The estimated minimum length of runs of homozygosity was around 1 Mb for yearling weight (YW) and average daily gain (ADG), and 4 Mb for birth weight (BW) and weaning weight (WW). The assessment of our proposed method showed its potential benefits in terms of the estimates of the genome-wide level of inbreeding as well as the calculation of inbreeding depression.

Technical Abstract: Pedigree information was traditionally used to assess inbreeding. Availability of high-density marker panels provides an alternative to assess inbreeding, particularly in the presence of incomplete and error-prone pedigrees. Assessment of autozygosity across chromosomal segments using runs of homozygosity (ROH) has emerged as a valuable tool to estimate inbreeding due to its general flexibility and ability to quantify chromosomal contribution to genome-wide inbreeding. Unfortunately, identifying ROH segments is sensitive to the parameters used during the search process. These parameters are heuristically set, leading to significant variation in the results. The minimum length required to identify a ROH segment has major effects on the estimation of inbreeding, yet it is arbitrarily set. To overcome this limitation, a search algorithm to approximate mutation loads was developed to determine the minimum length of ROH segments. It consists in finding genome segments with significant effect differences in trait means between animals with high and low autozygosity intervals at certain threshold values. The minimum length could be determined heuristically as the smallest interval at which a significant signal is detected. The proposed method was tested in an inbred Hereford cattle population genotyped for 30,220 SNPs. Phenotypes recorded for six traits were used for the approximation of mutation loads. The estimated minimum length was around 1 Mb for yearling weight (YW) and average daily gain (ADG), and 4 Mb for birth weight (BW) and weaning weight (WW). These trait-specific thresholds estimated using the proposed method could be attributed to a trait-dependent effects of homozygosity. The onset of significant inbreeding effects was well aligned with the estimated thresholds, especially for YW and ADG. Although highly deleterious alleles are expected to be more frequent in recent inbreeding (long ROH), short ROH segments (< 5 Mb) could contain a large number of less deleterious mutations with substantial joint effects on some traits (YW and ADG). Our results highlight the importance of accurate estimation of the ROH-based inbreeding and the necessity to consider a trait-specific minimum length threshold for the identification of ROH segments in inbreeding depression analyses. These thresholds could be determined using the proposed method provided the availability of phenotypic information.