identity‐by‐descent; inbreeding prediction; management of diversity; small effective population size; Biotechnology; Ecology, Evolution, Behavior and Systematics; Genetics
Abstract :
[en] In populations of small effective size (Ne), such as those in conservation programmes, companion animals or livestock species, inbreeding control is essential. Homozygosity-by-descent (HBD) segments provide relevant information in that context, as they allow accurate estimation of the inbreeding coefficient, provide locus-specific information and their length is informative about the "age" of inbreeding. Our objective was to evaluate tools for predicting HBD in future offspring based on parental genotypes, a problem equivalent to identifying segments identical-by-descent (IBD) among the four parental chromosomes. In total, we reviewed and evaluated 16 approaches using simulated and real data from populations with small Ne. The methods included model-based approaches as well as more computationally efficient rule-based approaches. The accuracy of the methods was then evaluated, including with low-density marker panels, genotyping-by-sequencing data and small groups of individuals, typical features of such populations. Two model-based approaches performed consistently well, while some rule-based approaches proved accurate for genome-wide predictions. The model-based approaches were particularly efficient when genomic information was sparse or degraded. Methods using phased data proved to be more accurate, while some approaches relying on unphased genotype data were sensitive to the assumed allele frequencies. In some settings, pedigree-based predictions ranked high for recent inbreeding levels. Finally, we showed that our evaluation is also informative about the accuracy of the methods for estimating relatedness and identifying IBD segments between pairs of present-day individuals. This study shows that future inbreeding can be accurately predicted, including at specific loci, but not all methods perform equally well.
Disciplines :
Animal production & animal husbandry Genetics & genetic processes Veterinary medicine & animal health
Author, co-author :
Forneris, Natalia ; Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA) ; Université de Liège - ULiège > GIGA > GIGA Molecular & Computational Biology - Unit of Animal Genomics
Bosse, Mirte ; Animal Breeding and Genomics, Wageningen University & Research, Wageningen, The Netherlands ; Amsterdam Institute for Life and Environment (A-LIFE), Section Ecology and Evolution, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Gautier, Mathieu ; CBGP, INRAE, CIRAD, IRD, L'institut Agro, Université de Montpellier, Montpellier, France
Druet, Tom ; Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA) ; Université de Liège - ULiège > GIGA > GIGA Molecular & Computational Biology - Unit of Animal Genomics
Language :
English
Title :
Genomic Prediction of Individual Inbreeding Levels for the Management of Genetic Diversity in Populations With Small Effective Size.
Publication date :
07 January 2025
Journal title :
Molecular Ecology Resources
ISSN :
1755-098X
eISSN :
1755-0998
Publisher :
John Wiley and Sons Inc, England
Pages :
e14068
Peer reviewed :
Peer Reviewed verified by ORBi
Tags :
CÉCI : Consortium des Équipements de Calcul Intensif
F.R.S.-FNRS - Fonds de la Recherche Scientifique SPW - Service Public de Wallonie
Funding text :
This work was supported by Fonds De La Recherche Scientifique\u2014FNRS, ROAGE T.0102.24. Service Public de Wallonie, BEWARE FitSel project\u2014convention no. 2110192. Funding:
Alemu, S. W., N. K. Kadri, C. Harland, et al. 2021. “An Evaluation of Inbreeding Measures Using a Whole-Genome Sequenced Cattle Pedigree.” Heredity 126, no. 3: 410–423. https://doi.org/10.1038/s41437-020-00383-9.
Baumdicker, F., G. Bisschop, D. Goldstein, et al. 2022. “Efficient Ancestry and Mutation Simulation With Msprime 1.0.” Genetics 220, no. 3: iyab229. https://doi.org/10.1093/genetics/iyab229.
Bertorelle, G., F. Raffini, M. Bosse, et al. 2022. “Genetic Load: Genomic Estimates and Applications in Non-Model Animals.” Nature Reviews Genetics 23, no. 8: 492–503. https://doi.org/10.1038/s41576-022-00448-x.
Bertrand, A. R., N. K. Kadri, L. Flori, M. Gautier, and T. Druet. 2019. “RZooRoH: An R Package to Characterize Individual Genomic Autozygosity and Identify Homozygous-By-Descent Segments.” Methods in Ecology and Evolution 10, no. 6: 860–866. https://doi.org/10.1111/2041-210X.13167.
Boichard, D., H. Chung, R. Dassonneville, et al. 2012. “Design of a Bovine Low-Density SNP Array Optimized for Imputation.” PLoS One 7, no. 3: e34130. https://doi.org/10.1371/journal.pone.0034130.
Bosse, M., H.-J. Megens, M. F. L. Derks, Á. M. R. de Cara, and M. A. M. Groenen. 2019. “Deleterious Alleles in the Context of Domestication, Inbreeding, and Selection.” Evolutionary Applications 12, no. 1: 6–17. https://doi.org/10.1111/eva.12691.
Bosse, M., H.-J. Megens, O. Madsen, et al. 2015. “Using Genome-Wide Measures of Coancestry to Maintain Diversity and Fitness in Endangered and Domestic Pig Populations.” Genome Research 25, no. 7: 970–981. https://doi.org/10.1101/gr.187039.114.
Broman, K. W., and J. L. Weber. 1999. “Long Homozygous Chromosomal Segments in Reference Families From the Centre d'Etude du Polymorphisme Humain.” American Journal of Human Genetics 65, no. 6: 1493–1500. https://doi.org/10.1086/302661.
Brown, M. D., C. G. Glazner, C. Zheng, and E. A. Thompson. 2012. “Inferring Coancestry in Population Samples in the Presence of Linkage Disequilibrium.” Genetics 190, no. 4: 1447–1460. https://doi.org/10.1534/genetics.111.137570.
Browning, B. L., and S. R. Browning. 2013. “Improving the Accuracy and Efficiency of Identity-By-Descent Detection in Population Data.” Genetics 194, no. 2: 459–471. https://doi.org/10.1534/genetics.113.150029.
Browning, B. L., X. Tian, Y. Zhou, and S. R. Browning. 2021. “Fast Two-Stage Phasing of Large-Scale Sequence Data.” American Journal of Human Genetics 108, no. 10: 1880–1890. https://doi.org/10.1016/j.ajhg.2021.08.005.
Caballero, A., A. Fernández, B. Villanueva, and M. A. Toro. 2022. “A Comparison of Marker-Based Estimators of Inbreeding and Inbreeding Depression.” Genetics, Selection, Evolution: GSE 54, no. 1: 82. https://doi.org/10.1186/s12711-022-00772-0.
Caballero, A., B. Villanueva, and T. Druet. 2021. “On the Estimation of Inbreeding Depression Using Different Measures of Inbreeding From Molecular Markers.” Evolutionary Applications 14, no. 2: 416–428. https://doi.org/10.1111/eva.13126.
de Cara, M. Á. R., B. Villanueva, M. Á. Toro, and J. Fernández. 2013. “Using Genomic Tools to Maintain Diversity and Fitness in Conservation Programmes.” Molecular Ecology 22, no. 24: 6091–6099. https://doi.org/10.1111/mec.12560.
Dimitromanolakis, A., A. D. Paterson, and L. Sun. 2019. “Fast and Accurate Shared Segment Detection and Relatedness Estimation in Un-Phased Genetic Data via TRUFFLE.” American Journal of Human Genetics 105, no. 1: 78–88. https://doi.org/10.1016/j.ajhg.2019.05.007.
Druet, T., and M. Gautier. 2017. “A Model-Based Approach to Characterize Individual Inbreeding at Both Global and Local Genomic Scales.” Molecular Ecology 26, no. 20: 5820–5841. https://doi.org/10.1111/mec.14324.
Druet, T., and M. Gautier. 2022. “A Hidden Markov Model to Estimate Homozygous-By-Descent Probabilities Associated With Nested Layers of Ancestors.” Theoretical Population Biology 145: 38–51. https://doi.org/10.1016/j.tpb.2022.03.001.
Druet, T., K. Oleński, L. Flori, et al. 2020. “Genomic Footprints of Recovery in the European Bison.” Journal of Heredity 111, no. 2: 194–203. https://doi.org/10.1093/jhered/esaa002.
Fitak, R. R., S. E. Rinkevich, and M. Culver. 2018a. “Genome-Wide Analysis of SNPs Is Consistent With No Domestic Dog Ancestry in the Endangered Mexican Wolf (Canis lupus baileyi).” Journal of Heredity 109, no. 4: 372–383. https://doi.org/10.1093/jhered/esy009.
Fitak, R. R., S. E. Rinkevich, and M. Culver. 2018b. “Data From: Genome-Wide Analysis of SNPs Is Consistent With No Domestic Dog Ancestry in the Endangered Mexican Wolf (Canis lupus baileyi) Dryad.” https://doi.org/10.5061/dryad.g68k008.
Freyman, W. A., K. F. McManus, S. S. Shringarpure, et al. 2021. “Fast and Robust Identity-By-Descent Inference With the Templated Positional Burrows-Wheeler Transform.” Molecular Biology and Evolution 38, no. 5: 2131–2151. https://doi.org/10.1093/molbev/msaa328.
Galla, S. J., L. Brown, T. E. Steeves, et al. 2022. “The Relevance of Pedigrees in the Conservation Genomics Era.” Molecular Ecology 31, no. 1: 41–54. https://doi.org/10.1111/mec.16192.
Gautier, M., K. Gharbi, T. Cezard, et al. 2013. “The Effect of RAD Allele Dropout on the Estimation of Genetic Variation Within and Between Populations.” Molecular Ecology 22, no. 11: 3165–3178. https://doi.org/10.1111/mec.12089.
Gengler, N., P. Mayeres, and M. Szydlowski. 2007. “A Simple Method to Approximate Gene Content in Large Pedigree Populations: Application to the Myostatin Gene in Dual-Purpose Belgian Blue Cattle. Animal: An International Journal of Animal.” Bioscience 1, no. 1: 21–28. https://doi.org/10.1017/S1751731107392628.
Gómez-Romano, F., B. Villanueva, J. Fernández, J. A. Woolliams, and R. Pong-Wong. 2016. “The Use of Genomic Coancestry Matrices in the Optimisation of Contributions to Maintain Genetic Diversity at Specific Regions of the Genome.” Genetics, Selection, Evolution: GSE 48: 2. https://doi.org/10.1186/s12711-015-0172-y.
Gusev, A., J. K. Lowe, M. Stoffel, et al. 2009. “Whole Population, Genome-Wide Mapping of Hidden Relatedness.” Genome Research 19, no. 2: 318–326. https://doi.org/10.1101/gr.081398.108.
Haller, B. C., J. Galloway, J. Kelleher, P. W. Messer, and P. L. Ralph. 2018. “Tree-Sequence Recording in SLiM Opens New Horizons for Forward-Time Simulation of Whole Genomes.” Molecular Ecology Resources 19, no. 2: 552–566. https://doi.org/10.1111/1755-0998.12968.
Haller, B. C., and P. W. Messer. 2023. “SLiM 4: Multispecies Eco-Evolutionary Modeling.” American Naturalist 201, no. 5: E127–E139. https://doi.org/10.1086/723601.
Han, L., and M. Abney. 2011. “Identity by Descent Estimation With Dense Genome-Wide Genotype Data.” Genetic Epidemiology 35, no. 6: 557–567. https://doi.org/10.1002/gepi.20606.
Han, L., and M. Abney. 2013. “Using Identity by Descent Estimation With Dense Genotype Data to Detect Positive Selection.” European Journal of Human Genetics 21, no. 2: 205–211. https://doi.org/10.1038/ejhg.2012.148.
Herten, K., M. S. Hestand, J. R. Vermeesch, and J. K. J. Van Houdt. 2015. “GBSX: A Toolkit for Experimental Design and Demultiplexing Genotyping by Sequencing Experiments.” BMC Bioinformatics 16, no. 1: 73. https://doi.org/10.1186/s12859-015-0514-3.
Hinrichs, D., T. H. E. Meuwissen, J. Ødegard, M. Holt, O. Vangen, and J. A. Woolliams. 2007. “Analysis of Inbreeding Depression in the First Litter Size of Mice in a Long-Term Selection Experiment With Respect to the Age of the Inbreeding.” Heredity 99, no. 1: 81–88. https://doi.org/10.1038/sj.hdy.6800968.
Jacquard, A. 1974. The Genetic Structure of Populations. New-York, NY: Springer-Verlag.
Kardos, M., H. R. Taylor, H. Ellegren, G. Luikart, and F. W. Allendorf. 2016. “Genomics Advances the Study of Inbreeding Depression in the Wild.” Evolutionary Applications 9, no. 10: 1205–1218. https://doi.org/10.1111/eva.12414.
Keller, L. F., and D. M. Waller. 2002. “Inbreeding Effects in Wild Populations.” Trends in Ecology & Evolution 17, no. 5: 230–241. https://doi.org/10.1016/S0169-5347(02)02489-8.
Keller, M. C., P. M. Visscher, and M. E. Goddard. 2011. “Quantification of Inbreeding Due to Distant Ancestors and Its Detection Using Dense Single Nucleotide Polymorphism Data.” Genetics 189, no. 1: 237–249. https://doi.org/10.1534/genetics.111.130922.
Kirin, M., R. McQuillan, C. S. Franklin, H. Campbell, P. M. McKeigue, and J. F. Wilson. 2010. “Genomic Runs of Homozygosity Record Population History and Consanguinity.” PLoS One 5, no. 11: e13996. https://doi.org/10.1371/journal.pone.0013996.
Lavanchy, E., and J. Goudet. 2023. “Effect of Reduced Genomic Representation on Using Runs of Homozygosity for Inbreeding Characterization.” Molecular Ecology Resources 23, no. 4: 787–802. https://doi.org/10.1111/1755-0998.13755.
Lee, Y. L., A. C. Bouwman, C. Harland, et al. 2023. “The Rate of de Novo Structural Variation Is Increased in In Vitro-Produced Offspring and Preferentially Affects the Paternal Genome.” Genome Research 33, no. 9: 1455–1464. https://doi.org/10.1101/gr.277884.123.
Leutenegger, A.-L., B. Prum, E. Génin, et al. 2003. “Estimation of the Inbreeding Coefficient Through Use of Genomic Data.” American Journal of Human Genetics 73, no. 3: 516–523. https://doi.org/10.1086/378207.
Li, C. C., and D. G. Horvitz. 1953. “Some Methods of Estimating the Inbreeding Coefficient.” American Journal of Human Genetics 5, no. 2: 107–117.
Lynch, M., and B. Walsh. 1998. “Genetics and Analysis of Quantitative Traits. Sinauer Associates.” https://scholar.google.com/scholar?hl=en&as_sdt=0,5&q=M.Lynch.Walsh+Genetics+and+analysis+of+quantitative+traits+1998+Sinauer+Associates.
Malécot, G. 1948. Les Mathématiques de l'hérédité. Paris: Masson et Cie. https://cir.nii.ac.jp/crid/1130000797475730048.
Malécot, G. 1967. Identical Loci and Relationship. Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability, edited by L. M. Le Cam and J. Neyman, vol. 4, 317–332. Berkeley, California: University of California Press. https://projecteuclid.org/accountAjax/Download?urlId=bsmsp%2F1200513803&downloadType=presschapter&isResultClick=True.
McQuillan, R., A.-L. Leutenegger, R. Abdel-Rahman, et al. 2008. “Runs of Homozygosity in European Populations.” American Journal of Human Genetics 83, no. 3: 359–372. https://doi.org/10.1016/j.ajhg.2008.08.007.
Meuwissen, T. H. E., A. K. Sonesson, G. Gebregiwergis, and J. A. Woolliams. 2020. “Management of Genetic Diversity in the Era of Genomics.” Frontiers in Genetics 11: 880. https://doi.org/10.3389/fgene.2020.00880.
Naji, M. M., J. L. Gualdrón Duarte, N. S. Forneris, and T. Druet. 2024. “Inbreeding Depression Is Associated With Recent Homozygous-By-Descent Segments in Belgian Blue Beef Cattle.” Genetics Selection Evolution 56, no. 1: 10. https://doi.org/10.1186/s12711-024-00878-7.
Narasimhan, V., P. Danecek, A. Scally, Y. Xue, C. Tyler-Smith, and R. Durbin. 2016. “BCFtools/RoH: A Hidden Markov Model Approach for Detecting Autozygosity From Next-Generation Sequencing Data.” Bioinformatics 32, no. 11: 1749–1751. https://doi.org/10.1093/bioinformatics/btw044.
Nietlisbach, P., S. Muff, J. M. Reid, M. C. Whitlock, and L. F. Keller. 2019. “Nonequivalent Lethal Equivalents: Models and Inbreeding Metrics for Unbiased Estimation of Inbreeding Load.” Evolutionary Applications 12, no. 2: 266–279. https://doi.org/10.1111/eva.12713.
Oget-Ebrad, C., N. K. Kadri, G. C. M. Moreira, et al. 2022. “Benchmarking Phasing Software With a Whole-Genome Sequenced Cattle Pedigree.” BMC Genomics 23: 130. https://doi.org/10.1186/s12864-022-08354-6.
Pemberton, T. J., D. Absher, M. W. Feldman, R. M. Myers, N. A. Rosenberg, and J. Z. Li. 2012. “Genomic Patterns of Homozygosity in Worldwide Human Populations.” American Journal of Human Genetics 91, no. 2: 275–292. https://doi.org/10.1016/j.ajhg.2012.06.014.
Pryce, J. E., B. J. Hayes, and M. E. Goddard. 2012. “Novel Strategies to Minimize Progeny Inbreeding While Maximizing Genetic Gain Using Genomic Information.” Journal of Dairy Science 95, no. 1: 377–388. https://doi.org/10.3168/jds.2011-4254.
Purcell, S., B. Neale, K. Todd-Brown, et al. 2007. “PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses.” American Journal of Human Genetics 81, no. 3: 559–575. https://doi.org/10.1086/519795.
Schäffer, A. A. 1999. “Computing Probabilities of Homozygosity by Descent.” Genetic Epidemiology 16, no. 2: 135–149. https://doi.org/10.1002/(SICI)1098-2272(1999)16:2<135::AID-GEPI2>3.0.CO;2-W.
Severson, A. L., T. S. Korneliussen, and I. Moltke. 2022. “LocalNgsRelate: A Software Tool for Inferring IBD Sharing Along the Genome Between Pairs of Individuals From Low-Depth NGS Data.” Bioinformatics 38, no. 4: 1159–1161. https://doi.org/10.1093/bioinformatics/btab732.
Solé, M., A.-S. Gori, P. Faux, et al. 2017. “Age-Based Partitioning of Individual Genomic Inbreeding Levels in Belgian Blue Cattle.” Genetics, Selection, Evolution: GSE 49, no. 1: 92. https://doi.org/10.1186/s12711-017-0370-x.
Stoffel, M. A., S. E. Johnston, J. G. Pilkington, and J. M. Pemberton. 2021. “Mutation Load Decreases With Haplotype Age in Wild Soay Sheep.” Evolution Letters 5, no. 3: 187–195. https://doi.org/10.1002/evl3.229.
Szpiech, Z. A., J. Xu, T. J. Pemberton, et al. 2013. “Long Runs of Homozygosity Are Enriched for Deleterious Variation.” American Journal of Human Genetics 93, no. 1: 90–102. https://doi.org/10.1016/j.ajhg.2013.05.003.
Teixeira, J. C., and C. D. Huber. 2021. “The Inflated Significance of Neutral Genetic Diversity in Conservation Genetics.” Proceedings of the National Academy of Sciences of the United States of America 118, no. 10: e2015096118. https://doi.org/10.1073/pnas.2015096118.
Thompson, E. A. 2008. “The IBD Process Along Four Chromosomes.” Theoretical Population Biology 73, no. 3: 369–373. https://doi.org/10.1016/j.tpb.2007.11.011.
Thompson, E. A. 2009. “Inferring Coancestry of Genome Segments in Populations. Invited Proceedings of the 57th Session of the International Statistical Institute, IPM13, Paper 0325. Durban, South Africa.” http://faculty.washington.edu/eathomp/Anonftp/Papers/ipm13_thompson.pdf.
VanRaden, P. M. 2008. “Efficient Methods to Compute Genomic Predictions.” Journal of Dairy Science 91, no. 11: 4414–4423. https://doi.org/10.3168/jds.2007-0980.
Vieira, F. G., A. Albrechtsen, and R. Nielsen. 2016. “Estimating IBD Tracts From Low Coverage NGS Data.” Bioinformatics (Oxford, England) 32, no. 14: 2096–2102. https://doi.org/10.1093/bioinformatics/btw212.
Wang, J. 2016. “Pedigrees or Markers: Which Are Better in Estimating Relatedness and Inbreeding Coefficient?” Theoretical Population Biology 107: 4–13. https://doi.org/10.1016/j.tpb.2015.08.006.
Woolliams, J. A., and T. H. E. Meuwissen. 2022. “Genetic Management Meets Genomics.” In Proceedings of the 12th World Congress of Genetics Applied to Livestock Production. Netherlands: Rotterdam. https://www.wageningenacademic.com/pb-assets/wagen/WCGALP2022/61_015.pdf.
Wright, S. 1922. “Coefficients of Inbreeding and Relationship.” American Naturalist 56, no. 645: 330–338. https://doi.org/10.1086/279872.
Yang, J., B. Benyamin, B. P. McEvoy, et al. 2010. “Common SNPs Explain a Large Proportion of the Heritability for Human Height.” Nature Genetics 42, no. 7: 565–569. https://doi.org/10.1038/ng.608.
Zhou, Y., S. R. Browning, and B. L. Browning. 2020. “A Fast and Simple Method for Detecting Identity-By-Descent Segments in Large-Scale Data.” American Journal of Human Genetics 106, no. 4: 426–437. https://doi.org/10.1016/j.ajhg.2020.02.010.