Runs of homozygosity: current knowledge and applications in livestock.

This review presents a broader approach to the implementation and study of runs of homozygosity (ROH) in animal populations, focusing on identifying and characterizing ROH and their practical implications. ROH are continuous homozygous segments that are common in individuals and populations. The ability of these homozygous segments to give insight into a population's genetic events makes them a useful tool that can provide information about the demographic evolution of a population over time. Furthermore, ROH provide useful information about the genetic relatedness among individuals, helping to minimize the inbreeding rate and also helping to expose deleterious variants in the genome. The frequency, size and distribution of ROH in the genome are influenced by factors such as natural and artificial selection, recombination, linkage disequilibrium, population structure, mutation rate and inbreeding level. Calculating the inbreeding coefficient from molecular information from ROH (FROH ) is more accurate for estimating autozygosity and for detecting both past and more recent inbreeding effects than are estimates from pedigree data (FPED ). The better results of FROH suggest that FROH can be used to infer information about the history and inbreeding levels of a population in the absence of genealogical information. The selection of superior animals has produced large phenotypic changes and has reshaped the ROH patterns in various regions of the genome. Additionally, selection increases homozygosity around the target locus, and deleterious variants are seen to occur more frequently in ROH regions. Studies involving ROH are increasingly common and provide valuable information about how the genome's architecture can disclose a population's genetic background. By revealing the molecular changes in populations over time, genome-wide information is crucial to understanding antecedent genome architecture and, therefore, to maintaining diversity and fitness in endangered livestock breeds.

[1]  H. Schwarzenbacher,et al.  zanardi: an open-source pipeline for multiple-species genomic analysis of SNP array data. , 2017, Animal genetics.

[2]  Lusheng Huang,et al.  Population structure and genome characterization of local pig breeds in Russia, Belorussia, Kazakhstan and Ukraine , 2016, Genetics Selection Evolution.

[3]  M. Rothschild,et al.  Multiple genomic signatures of selection in goats and sheep indigenous to a hot arid environment , 2015, Heredity.

[4]  J. Williams,et al.  Inbreeding and purging at the genomic Level: the Chillingham cattle reveal extensive, non-random SNP heterozygosity. , 2016, Animal genetics.

[5]  A. Stella,et al.  Using runs of homozygosity to detect genomic regions associated with susceptibility to infectious and metabolic diseases in dairy cows under intensive farming conditions , 2016, 1601.07062.

[6]  José Fernando Garcia,et al.  Development and implementation of genomic predictions in beef cattle , 2016 .

[7]  J. Woolliams,et al.  The use of genomic coancestry matrices in the optimisation of contributions to maintain genetic diversity at specific regions of the genome , 2016, Genetics Selection Evolution.

[8]  T. Marquès-Bonet,et al.  Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs , 2015, Proceedings of the National Academy of Sciences.

[9]  C. Gondro,et al.  Genome-wide linkage disequilibrium and genetic diversity in five populations of Australian domestic sheep , 2015, Genetics Selection Evolution.

[10]  M. Gut,et al.  Runs of homozygosity reveal signatures of positive selection for reproduction traits in breed and non-breed horses , 2015, BMC Genomics.

[11]  J. Sölkner,et al.  GENOMIC BACKGROUND OF ENTROPION IN FLECKVIEH CATTLE , 2015 .

[12]  G. Wiggans,et al.  The Relationship between Runs of Homozygosity and Inbreeding in Jersey Cattle under Selection , 2015, PloS one.

[13]  M. D. de Cara,et al.  Using genome-wide measures of coancestry to maintain diversity and fitness in endangered and domestic pig populations , 2015, Genome research.

[14]  J. Kijas,et al.  Population structure and history of the Welsh sheep breeds determined by whole genome genotyping , 2015, BMC Genetics.

[15]  H. Neves,et al.  Preliminary study to determine extent of linkage disequilibrium and estimates of autozygosity in Brazilian Gyr dairy cattle , 2015 .

[16]  A. Stella,et al.  M´ as all´ a del GWAS: alternativas para localizar QTLs , 2015, 1504.03802.

[17]  P. Zandi,et al.  Whole-genome CNV analysis: advances in computational approaches , 2015, Front. Genet..

[18]  P. Ajmone-Marsan,et al.  Analysis of runs of homozygosity and their relationship with inbreeding in five cattle breeds farmed in Italy. , 2015, Animal genetics.

[19]  A. Stella,et al.  Challenges and opportunities in genetic improvement of local livestock breeds , 2015, Front. Genet..

[20]  A. Stella,et al.  Predicting haplotype carriers from SNP genotypes in Bos taurus through linear discriminant analysis , 2015, Genetics Selection Evolution.

[21]  C. V. Van Tassell,et al.  Assessment of autozygosity in Nellore cows (Bos indicus) through high-density SNP genotypes , 2015, Front. Genet..

[22]  M. D. de Cara,et al.  Detecting inbreeding depression for reproductive traits in Iberian pigs using genome-wide data , 2015, Genetics Selection Evolution.

[23]  B. Guldbrandtsen,et al.  Runs of homozygosity and distribution of functional variants in the cattle genome , 2014, BMC Genomics.

[24]  C. Ponting,et al.  RBFOX and PTBP1 proteins regulate the alternative splicing of micro-exons in human brain transcripts , 2015, Genome research.

[25]  Leif Andersson,et al.  Prehistoric genomes reveal the genetic foundation and cost of horse domestication , 2014, Proceedings of the National Academy of Sciences.

[26]  M. Goddard,et al.  Identification of genomic regions associated with inbreeding depression in Holstein and Jersey dairy cattle , 2014, Genetics Selection Evolution.

[27]  Genomic prediction based on runs of homozygosity , 2014, Genetics Selection Evolution.

[28]  A. Stella,et al.  Applying Runs of Homozygosity to the Detection of Associations between Genotype and Phenotype in Farm Animals , 2014 .

[29]  Yi Zhang.  Inbreeding by pedigree and genomic markers in selection lines of pigs , 2014 .

[30]  J. Sölkner,et al.  Inbreeding and runs of homozygosity: A possible solution to an old problem , 2014 .

[31]  M. Rothschild,et al.  Applications of genomics to improve livestock in the developing world , 2014 .

[32]  A. Magi,et al.  Detection of Runs of Homozygosity from Whole Exome Sequencing Data: State of the Art and Perspectives for Clinical, Population and Epidemiological Studies , 2014, Human Heredity.

[33]  C. V. Van Tassell,et al.  Genome-wide association study and ancestral origins of the slick-hair coat in tropically adapted cattle , 2014, Front. Genet..

[34]  C. Gaskins,et al.  Estimation of inbreeding and effective population size of full-blood Wagyu cattle registered with the American Wagyu Cattle Association. , 2014, Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie.

[35]  S. Abegaz,et al.  Design of community based breeding programs for two indigenous goat breeds of Ethiopia , 2014 .

[36]  J. Pérez-Ortín,et al.  Cytoplasmic 5′-3′ exonuclease Xrn1p is also a genome-wide transcription factor in yeast , 2013, Front. Genet..

[37]  María Ángeles Rodríguez Cara,et al.  Using genomic tools to maintain diversity and fitness in conservation programmes , 2013, Molecular ecology.

[38]  G. Wiggans,et al.  Effect of Artificial Selection on Runs of Homozygosity in U.S. Holstein Cattle , 2013, PloS one.

[39]  M. Groenen,et al.  Conservation genomic analysis of domestic and wild pig populations from the Iberian Peninsula , 2013, BMC Genetics.

[40]  Johann Sölkner,et al.  Estimating autozygosity from high-throughput information: effects of SNP density and genotyping errors , 2013, Genetics Selection Evolution.

[41]  C. Óvilo,et al.  Measuring inbreeding and inbreeding depression on pig growth from pedigree or SNP-derived metrics. , 2013, Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie.

[42]  J. Sölkner,et al.  Estimates of autozygosity derived from runs of homozygosity: empirical evidence from selected cattle populations. , 2013, Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie.

[43]  Zachary A. Szpiech,et al.  Long runs of homozygosity are enriched for deleterious variation. , 2013, American journal of human genetics.

[44]  M. Goddard,et al.  Inferring Demography from Runs of Homozygosity in Whole-Genome Sequence, with Correction for Sequence Errors , 2013, Molecular biology and evolution.

[45]  Anas M. Khanshour.  Genetic Diversity and Population Structure of the Arabian Horse Populations from Syria and other Countries , 2013 .

[46]  K. Weigel,et al.  Evaluation of inbreeding depression in Holstein cattle using whole-genome SNP markers and alternative measures of genomic inbreeding. , 2013, Journal of dairy science.

[47]  E. G. Cothran,et al.  Microsatellite analysis of genetic diversity and population structure of Arabian horse populations. , 2013, The Journal of heredity.

[48]  Ye Zhao,et al.  cgaTOH: Extended Approach for Identifying Tracts of Homozygosity , 2013, PloS one.

[49]  Lusheng Huang,et al.  Genetic Diversity, Linkage Disequilibrium and Selection Signatures in Chinese and Western Pigs Revealed by Genome-Wide SNP Markers , 2013, PloS one.

[50]  M. Groenen,et al.  Regions of Homozygosity in the Porcine Genome: Consequence of Demography and the Recombination Landscape , 2012, PLoS genetics.

[51]  Bronwen L. Aken,et al.  Analyses of pig genomes provide insight into porcine demography and evolution , 2012, Nature.

[52]  D. Bradley,et al.  Runs of homozygosity and population history in cattle , 2012, BMC Genetics.

[53]  Richard M Myers,et al.  Genomic patterns of homozygosity in worldwide human populations. , 2012, American journal of human genetics.

[54]  Ismo Strandén,et al.  A Comparison of Approaches to Estimate the Inbreeding Coefficient and Pairwise Relatedness Using Genomic and Pedigree Data in a Sheep Population , 2011, PloS one.

[55]  Matthew C Keller,et al.  Detecting autozygosity through runs of homozygosity: A comparison of three autozygosity detection algorithms , 2011, BMC Genomics.

[56]  P. Visscher,et al.  Quantification of Inbreeding Due to Distant Ancestors and Its Detection Using Dense Single Nucleotide Polymorphism Data , 2011, Genetics.

[57]  M. Tapio,et al.  Extent of linkage disequilibrium and effective population size in Finnish Landrace and Finnish Yorkshire pig breeds. , 2011, Journal of animal science.

[58]  Harry Campbell,et al.  Genomic Runs of Homozygosity Record Population History and Consanguinity , 2010, PloS one.

[59]  J. Woolliams,et al.  Linkage disequilibrium and historical effective population size in the Thoroughbred horse. , 2010, Animal genetics.

[60]  L. Varona,et al.  A note on mate allocation for dominance handling in genomic selection , 2010, Genetics Selection Evolution.

[61]  M. Krawczak,et al.  Genomic and geographic distribution of SNP-defined runs of homozygosity in Europeans. , 2010, Human molecular genetics.

[62]  Brian L. Browning,et al.  High-resolution detection of identity by descent in unrelated individuals. , 2010, American journal of human genetics.

[63]  N. J. Ouborg,et al.  Conservation genetics in transition to conservation genomics. , 2010, Trends in genetics : TIG.

[64]  J. Sölkner,et al.  Genomic metrics of individual autozygosity, applied to a cattle population , 2010 .

[65]  J. Woolliams,et al.  Maximising genetic gain whilst controlling rates of genomic inbreeding using genomicoptimum contribution selection , 2010 .

[66]  Y. Pawitan,et al.  Regions of homozygosity and their impact on complex diseases and traits , 2010, Human Genetics.

[67]  I. Rudan,et al.  Comparative assessment of methods for estimating individual genome-wide homozygosity-by-descent from human genomic data , 2010, BMC Genomics.

[68]  Hans H. Cheng,et al.  Comparison of linkage disequilibrium and haplotype diversity on macro- and microchromosomes in chicken , 2009, BMC Genetics.

[69]  D. Charlesworth,et al.  The genetics of inbreeding depression , 2009, Nature Reviews Genetics.

[70]  Stéphanie Leocard.  Selective sweep and the size of the hitchhiking set , 2009, Advances in Applied Probability.

[71]  Peter J. Bradbury,et al.  The Last Glacial Maximum , 2009, Science.

[72]  P. Sklar,et al.  No evidence for excess runs of homozygosity in bipolar disorder , 2009, Psychiatric genetics.

[73]  C. Fonseca,et al.  Genetic structure of the wild boar population in Portugal: Evidence of a recent bottleneck , 2009 .

[74]  N. Orr,et al.  A Genome Scan for Positive Selection in Thoroughbred Horses , 2009, PloS one.

[75]  Peter Nürnberg,et al.  HomozygosityMapper—an interactive approach to homozygosity mapping , 2009, Nucleic Acids Res..

[76]  M. Nalls,et al.  Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer’s disease , 2009, neurogenetics.

[77]  Alexander Gusev,et al.  Whole population, genome-wide mapping of hidden relatedness. , 2009, Genome research.

[78]  Hans H. Cheng,et al.  Genome-wide assessment of worldwide chicken SNP genetic diversity indicates significant absence of rare alleles in commercial breeds , 2008, Proceedings of the National Academy of Sciences.

[79]  Igor Rudan,et al.  Runs of homozygosity in European populations. , 2008, American journal of human genetics.

[80]  M. Goddard,et al.  Linkage Disequilibrium and Persistence of Phase in Holstein–Friesian, Jersey and Angus Cattle , 2008, Genetics.

[81]  D. Gottschling,et al.  A Genetic Screen for Increased Loss of Heterozygosity in Saccharomyces cerevisiae , 2008, Genetics.

[82]  Todd Lencz,et al.  Runs of homozygosity reveal highly penetrant recessive loci in schizophrenia , 2007, Proceedings of the National Academy of Sciences.

[83]  E. López de Maturana,et al.  Inbreeding depression on female fertility and calving ease in Spanish dairy cattle. , 2007, Journal of dairy science.

[84]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[85]  J. Weber,et al.  Estimating Human Inbreeding Coefficients: Comparison of Genealogical and Marker Heterozygosity Approaches , 2006, Annals of human genetics.

[86]  N. Morton,et al.  Extended tracts of homozygosity in outbred human populations. , 2006, Human molecular genetics.

[87]  Manuel A. R. Ferreira,et al.  Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings , 2006, PLoS genetics.

[88]  J. Foulley,et al.  Aggregate diversity: New approach combining within- and between-breed genetic diversity , 2005 .

[89]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[90]  C. Drögemüller,et al.  Genetic diversity in German draught horse breeds compared with a group of primitive, riding and wild horses by means of microsatellite DNA markers. , 2004, Animal genetics.

[91]  Jin-Tang Dong.  Chromosomal Deletions and Tumor Suppressor Genes in Prostate Cancer , 2004, Cancer and Metastasis Reviews.

[92]  L. Keller,et al.  Inbreeding effects in wild populations. , 2002 .

[93]  J. Sölkner,et al.  Effects of models with finite loci, selection, dominance, epistasis and linkage on inbreeding coefficients based on pedigree and genotypic information , 2002 .

[94]  K. Anyane-Yeboa,et al.  Homozygosity for multiple contiguous single-nucleotide polymorphisms as an indicator of large heterozygous deletions: identification of a novel heterozygous 8-kb intragenic deletion (IVS7-19 to IVS15-17) in a patient with glycogen storage disease type II. , 2002, American journal of human genetics.

[95]  C. Bendixen,et al.  Complex Vertebral Malformation in Holstein Calves , 2001, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[96]  J. Weber,et al.  Long homozygous chromosomal segments in reference families from the centre d'Etude du polymorphisme humain. , 1999, American journal of human genetics.

[97]  Richard Frankham,et al.  Conservation biology: Inbreeding leads to extinction , 1998, Nature.

[98]  P. Brakefield,et al.  SEVERE INBREEDING DEPRESSION AND RAPID FITNESS REBOUND IN THE BUTTERFLY BICYCLUS ANYNANA (SATYRIDAE) , 1996, Evolution; international journal of organic evolution.

[99]  J. Weller,et al.  Misidentification rate in the Israeli dairy cattle population and its implications for genetic improvement. , 1996, Journal of dairy science.

[100]  S. Hall,et al.  Inbreeding and population dynamics of the Chillingham cattle (Bos taurus) , 1988 .

[101]  E. Randi,et al.  The systematics of the wild boar (Sus scrofa L.) in Italy , 1988 .

[102]  M Terada,et al.  Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[103]  E S Lander,et al.  Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. , 1987, Science.

[104]  F. Allendorf.  Genetic drift and the loss of alleles versus heterozygosity , 1986 .

[105]  N. Copeland,et al.  Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism , 1985, Nature.

[106]  E. Engel,et al.  A new genetic concept: uniparental disomy and its potential effect, isodisomy. , 1980, American journal of medical genetics.

[107]  A. Garrod.  The Incidence of Alkaptonuria: A study in Chemical Individuality , 1996, Nutrition reviews.

[108]  J. Lush,et al.  A GENETIC HISTORY OF THE BROWN SWISS CATTLE IN THE UNITED STATES , 1937 .

[109]  Sewall Wright,et al.  Coefficients of Inbreeding and Relationship , 1922, The American Naturalist.