Identification of unique ROH regions with unfavorable effects on production and fertility traits in Canadian Holsteins

Abstract

Background The advent of genomic information and the reduction in the cost of genotyping have led to the use of genomic information to estimate genomic inbreeding as an alternative to pedigree inbreeding. Using genomic measures, effects of genomic inbreeding on production and fertility traits have been observed. However, there have been limited studies on the specific genomic regions causing the observed negative association with the trait of interest. Our aim was to identify unique run of homozygosity (ROH) genotypes present within a given genomic window that display negative associations with production and fertility traits and to quantify the effects of these identified ROH genotypes. Methods In total, 50,575 genotypes based on a 50K single nucleotide polymorphism (SNP) array and 259,871 pedigree records were available. Of these 50,575 genotypes, 46,430 cows with phenotypic records for production and fertility traits and having a first calving date between 2008 and 2018 were available. Unique ROH genotypes identified using a sliding-window approach were fitted into an animal mixed model as fixed effects to determine their effect on production and fertility traits. Results In total, 133 and 34 unique ROH genotypes with unfavorable effects were identified for production and fertility traits, respectively, at a 1% genome-wise false discovery rate. Most of these ROH regions were located on bovine chromosomes 8, 13, 14 and 19 for both production and fertility traits. For production traits, the average of all the unfavorably identified unique ROH genotypes effects were estimated to decrease milk yield by 247.30 kg, fat yield by 11.46 kg and protein yield by 8.11 kg. Similarly, for fertility traits, an average 4.81-day extension in first service to conception, a 0.16 increase in number of services, and a − 0.07 incidence in 56-day non-return rate were observed. Furthermore, a ROH region located on bovine chromosome 19 was identified that, when homozygous, had a negative effect on production traits. Signatures of selection proximate to this region have implicated GH1 as a potential candidate gene, which encodes the growth hormone that binds the growth hormone receptor. This observed negative effect could be a consequence of unfavorable alleles in linkage disequilibrium with favorable alleles. Conclusions ROH genotypes with unfavorable effects on production and fertility traits were identified within and across multiple traits on most chromosomes. These identified ROH genotypes could be included in mate selection programs to minimize their frequency in future generations.

Assessment of Heterozygosity and Genome-Wide Analysis of Heterozygosity Regions in Two Duroc Pig Populations

“…The important economic traits of Duroc pigs are affected by strong artificial selection, which can lead to reduced polymorphism in regions near the selected areas due to linkage disequilibrium (LD). Previous literature ( Makanjuola et al, 2021 ; Zhao et al, 2021 ) reported that some homozygous regions had adverse effects on production and fertility traits in cattle, which may be caused by the increase of unfavorable alleles in LD with benefit alleles during intense selection. Therefore, maintaining genomic heterozygosity within commercial breeds is critical to the sustainability of livestock farming ( Williams et al, 2016 ), and ROHet may be a measure for investigating and managing the genetic diversity of Duroc populations in this study.…”

Identification of Homozygous Regions With Adverse Effects on the Five Economic Traits of Duroc Pigs

“…These provide excellent experimental materials for estimating the association between ROH and phenotypes. Considering that Howard et al ( 21 ), Martikainen et al ( 22 ), and Makanjuola et al ( 23 ) successfully detected unique ROH genotypes with adverse effects on the production and fertility traits of Landrace and Large White pigs, Finnish Ayrshire cattle, and Canadian Holsteins cow, respectively. We used the same HaploFinder software to identify unfavorable ROH genotypes within traits and across multiple traits.…”

“…The results showed that S21 had more total unfavorable ROHs on five traits than that of S22 population. According to previous description ( 23 ), stringent criteria with a significant threshold of FDR = 0.01 and at least 50 SNPs in a ROH were used to identify significantly unfavorable ROH regions in two Duroc lines. Although these options may ignore some valuable genotypes, the regions we detected were expected to be the most deleterious to the phenotypes and were formed in recent generations.…”

“…Since Bonferroni correction is a relatively strict criterion for multiple testing ( 31 , 36 ), a false discovery rate (FDR) = 0.01 was used in this study to determine the threshold p -value of significant ROH regions. Considering that recent inbreeding has more adverse effects compared to ancient inbreeding ( 37 ), we then retained significantly unfavorable ROHs with a minimum of 50 SNPs following the previous literature ( 23 ), because such a window size captures the more recent inbreeding ( 38 ). R package ggplot was employed to plot the candidate ROHs of the phenotypic traits in two Duroc lines.…”

“…For example, Howard et al ( 21 ) developed an algorithm of Unfavorable Haplotype Finder software ( Haplofinder ) that can detect unfavorable ROH genotypes associated with phenotypes. Then, Martikainen et al ( 22 ) used Haplofinder software to identify ROH fragments that were not conducive to the fertility and milk production of Finnish Ayrshire cattle; Makanjuola et al ( 23 ) used same software to uncover unique ROH segments with adverse effects on fertility and production traits in Canadian Holstein cattle.…”