Symposium review: The genomic architecture of inbreeding: How homozygosity affects health and performance

Inbreeding depression is a growing concern in livestock because it can detrimentally affect animal fitness, health, and production levels. Genomic information can be used to more effectively capture variance in Mendelian sampling, thereby enabling more accurate estimation of inbreeding, but further progress is still required. The calculation of inbreeding for herd management purposes is largely still done using pedigree information only, although inbreeding coefficients calculated in this manner have been shown to be less accurate than genomic inbreeding measures. Continuous stretches of homozygous genotypes, so called runs of homozygosity, have been shown to provide a better estimate of autozygosity at the genomic level than conventional measures based on inbreeding coefficients calculated through conventional pedigree information or even genomic relationship matrices. For improved and targeted management of genomic inbreeding at the population level, the development of methods that incorporate genomic information in mate selection programs may provide a more precise tool for reducing the detrimental effects of inbreeding in dairy herds. Additionally, a better understanding of the genomic architecture of inbreeding and incorporating that knowledge into breeding programs could significantly refine current practices. Opportunities to maintain high levels of genetic progress in traits of interest while managing homozygosity and sustaining acceptable levels of heterozygosity in highly selected dairy populations exist and should be examined more closely for continued sustainability of both the dairy cattle population as well as the dairy industry. The inclusion of precise genomic measures of inbreeding, such as runs of homozygosity, inbreeding, and mating programs, may provide a path forward. In this symposium review article, we describe traditional measures of inbreeding and the recent developments made toward more precise measures of homozygosity using genomic information. The effects of homozygosity resulting from inbreeding on phenotypes, the identification and mapping of detrimental homozygosity haplotypes, management of inbreeding with genomic data, and areas in need of further research are discussed.     

How genomic selection has increased rates of genetic gain and inbreeding in the Australian national herd,genomic information nucleus,and bulls

Genomic selection has been commonly used for selection for over a decade. In this time, the rate of genetic gain has more than doubled in some countries, while inbreeding per year has also increased. Inbreeding can result in a loss of genetic diversity, decreased long-term response to selection, reduced animal performance and ultimately, decreased farm profitability. We quantified and compared changes in genetic gain and diversity resulting from genomic selection in Australian Holstein and Jersey cattle populations. To increase the accuracy of genomic selection, Australia has had a female genomic reference population since 2013, specifically designed to be representative of commercial populations and thus including both Holstein and Jersey cows. Herds that kept excellent health and fertility data were invited to join this population and most their animals were genotyped. In both breeds, the rate of genetic gain and inbreeding was greatest in bulls, and then the female genomic reference population, and finally the wider national herd. When comparing pre- and postgenomic selection, the rates of genetic gain for the national economic index has increased by ~160% in Holstein females and ~100% in Jersey females. This has been accompanied by doubling of the rates of inbreeding in female populations, and the rate of inbreeding has increased several fold in Holstein bulls since the widespread use of genomic selection. Where cow genotype data were available to perform a more accurate genomic analysis, greater rates of pedigree and genomic inbreeding were observed, indicating actual inbreeding levels could be underestimated in the national population due to gaps in pedigrees. Based on current rates of genetic gain, the female reference population is progressing ahead of the national herd and could be used to infer and track the future inbreeding and genetic trends of the national herds.     

Comparative analysis of inbreeding parameters and runs of homozygosity islands in 2 Italian autochthonous cattle breeds mainly raised in the Parmigiano-Reggiano cheese production region

Reggiana and Modenese are autochthonous cattle breeds, reared in the North of Italy, that can be mainly distinguished for their standard coat color (Reggiana is red, whereas Modenese is white with some pale gray shades). Almost all milk produced by these breeds is transformed into 2 mono-breed branded Parmigiano-Reggiano cheeses, from which farmers receive the economic incomes needed for the sustainable conservation of these animal genetic resources. After the setting up of their herd books in 1960s, these breeds experienced a strong reduction in the population size that was subsequently reverted starting in the 1990s (Reggiana) or more recently (Modenese) reaching at present a total of about 2,800 and 500 registered cows, respectively. Due to the small population size of these breeds, inbreeding is a very important cause of concern for their conservation programs. Inbreeding is traditionally estimated using pedigree data, which are summarized in an inbreeding coefficient calculated at the individual level (F_PED). However, incompleteness of pedigree information and registration errors can affect the effectiveness of conservation strategies. High-throughput SNP genotyping platforms allow investigation of inbreeding using genome information that can overcome the limits of pedigree data. Several approaches have been proposed to estimate genomic inbreeding, with the use of runs of homozygosity (ROH) considered to be the more appropriate. In this study, several pedigree and genomic inbreeding parameters, calculated using the whole herd book populations or considering genotyping information (GeneSeek GGP Bovine 150K) from 1,684 Reggiana cattle and 323 Modenese cattle, were compared. Average inbreeding values per year were used to calculate effective population size. Reggiana breed had generally lower genomic inbreeding values than Modenese breed. The low correlation between pedigree-based and genomic-based parameters (ranging from 0.187 to 0.195 and 0.319 to 0.323 in the Reggiana and Modenese breeds, respectively) reflected the common problems of local populations in which pedigree records are not complete. The high proportion of short ROH over the total number of ROH indicates no major recent inbreeding events in both breeds. ROH islands spread over the genome of the 2 breeds (15 in Reggiana and 14 in Modenese) identified several signatures of selection. Some of these included genes affecting milk production traits, stature, body conformation traits (with a main ROH island in both breeds on BTA6 containing the ABCG2, NCAPG, and LCORL genes) and coat color (on BTA13 in Modenese containing the ASIP gene). In conclusion, this work provides an extensive comparative analysis of pedigree and genomic inbreeding parameters and relevant genomic information that will be useful in the conservation strategies of these 2 iconic local cattle breeds.     

Inbreeding and effective population size in French dairy sheep: Comparison between genomic and pedigree estimates

Before availability of dense SNP data, genetic diversity was characterized and managed with pedigree-based information. Besides this classical approach, 2 methodologies have been proposed in recent years to characterize and manage diversity from dense SNP data: the SNP-by-SNP approach and the alternative based on runs of homozygosity (ROH). The establishment of criteria to identify ROH is a current constraint in the literature dealing with ROH. The objective of this study was, using a medium-density SNP chip, to quantify by 3 methods (pedigree, SNP-by-SNP, and ROH) the genetic diversity on 5 selected French dairy sheep subpopulations and breeds and to assess the effect of the definition of ROH on these estimates. The data set available included individuals from the breeds Basco-Béarnaise, Manech Tête Noire, Manech Tête Rousse, and 2 subpopulations of Lacaune: Lacaune Confederation and Lacaune Ovitest. Animals were genotyped with the Illumina OvineSNP50 BeadChip (Illumina Inc., San Diego, CA). After filtering, the genomic data included 38,287 autosomal SNP and 8,700 individuals, which comprised 72,803 animals in the pedigree. The results indicated that no significant differences were observed in effective population size estimates obtained from pedigree or genomic (SNP-by-SNP or ROH) information. In general, estimates of effective population size were above 200 in Lacaune Confederation and Lacaune Ovitest subpopulations and below 200 in Basco-Béarnaise, Manech Tête Noire, and Manech Tête Rousse breeds. The minimum length that constituted a ROH, the minimum number of SNP that constituted a ROH, as well as the minimum density and the maximum distance allowed between 2 homozygous SNP are ROH-defining factors with important implications in the estimation of the rate of inbreeding. The ROH-based rates of inbreeding in concordance with those obtained from pedigree information require a specific set of values. This particular set of values is different from that identified to obtain ROH-based rates of inbreeding similar to those obtained on a SNP-by-SNP basis. Factors to define ROH do not change the results much unless extreme values are considered, although further research on ROH-based inbreeding is still required.     

Inbreeding trends and application of optimized selection in the UK Holstein population

Important increases in the rates of inbreeding have recently been observed in dairy cattle populations, and methods have been proposed to address these increases. The aims of this study were to estimate the current level and rates of inbreeding in the UK Holstein population and to investigate the potential of applying optimized selection to manage the rates of inbreeding. Inbreeding coefficients were calculated for the entire UK Holstein population using 1940 as the base year. Rates of inbreeding were obtained for 3 time periods by regressing mean inbreeding coefficients on the year of birth of the animals. The expected average pedigree index and expected inbreeding of offspring using optimized contributions for a given set of selection candidates was compared to the expected pedigree index and inbreeding of offspring for the same set of selection candidates using observed contributions. The rate of inbreeding in the UK Holstein population has increased substantially since 1990 when compared to previous time periods. This increase is most likely due to the large influence of a few related sires on the breed in the mid- to late 1980s. The introduction of the individual animal model in the early 1990s may also have contributed to increased inbreeding. Optimized selection appears to represent a promising selection tool, not only to manage rates of inbreeding, but also to increase genetic gain at the same rate of inbreeding.     

Inbreeding coefficients and runs of homozygosity islands in Brazilian water buffalo

Characterization of autozygosity is relevant to monitor genetic diversity and manage inbreeding levels in breeding programs. Identification of autozygosity hotspots can unravel genomic regions targeted by selection for economically important traits and can help identify candidate genes for selection. In this study, we estimated the inbreeding levels of a Brazilian population of Murrah buffalo undergoing selection for milk production traits, particularly milk yield. We also studied the distribution of runs of homozygosity (ROH) islands and identified putative genes and quantitative trait loci (QTL) under selection. We genotyped 422 Murrah buffalo for 51,611 SNP; 350 of these had ROH longer than 10 Mb, indicating the occurrence of inbreeding in the last 5 generations. The mean length of the ROH per animal was 4.28 ± 1.85 Mb. Inbreeding coefficients were calculated from the genomic relationship matrix, the pedigree, and the ROH, with estimates varying between 0.242 and 0.035. Inbreeding estimates from the pedigree had a low correlation with the genomic estimates, and estimates from the genomic relationship matrix were much higher than those from the pedigree or the ROH. Signatures of selection were identified in 6 genomic regions, located on chromosomes 1, 2, 3, 5, 16, and 18, encompassing a total of 190 genes and 174 QTL. Many of the genes (e.g., APRT and ACSF3) and QTL identified are related to milk production traits, such as milk yield, milk fat yield and percentage, and milk protein yield and percentage. Other genes are associated with reproduction and immune response traits as well as morphological aspects of the buffalo species. Inbreeding levels in this population are still low but are increasing due to selection and should be managed to avoid future losses due to inbreeding depression. The proximity of genes linked to milk production traits with genes associated with reproduction and immune system traits suggests the need to include these latter genes in the breeding program to avoid negatively affecting them due to selection for production traits.     

Controlling Inbreeding in Modern Breeding Programs

Modern livestock breeding programs feature accurate breeding value estimation and advanced reproductive technology. Such programs lead to rapid genetic progress, but they also lead to the accumulation of inbreeding via heavy impact of a few selected individuals or families. Inbreeding rates are accelerating in most species, and economic losses due to inbreeding depression in production, growth, health, and fertility are a serious concern. Most research has focused on preservation of rare breeds or maintenance of genetic diversity within closed nucleus breeding schemes. However, the apparently large population size of many livestock breeds is misleading, because inbreeding is primarily a function of selection intensity. Strategies for maintaining variation by restricting relationships between selected animals or by artificially increasing the emphasis on within-family information when estimating breeding values have been suggested, and some approaches seem to provide greater long-term responses than BLUP selection. Corrective mating programs are widely used in some species, and these can be modified to consider selection for economic merit adjusted for inbreeding depression. Selection of parents of AI bulls based on optimal genetic contributions to future generations, which are a function of estimated breeding values and genetic relationships between selected individuals, appears most promising. Rapid implementation of such procedures is necessary to avoid further reductions in effective population size. Missing pedigree information is a problem in practice, and the low net present value of future genetic gains makes it difficult for breeding companies to sacrifice short-term economic gains in favor of long-term diversity issues.     

A mating advice system in dairy cattle incorporating genomic information

This study investigated the effects of alternative mating programs that incorporate genomic information on expected progeny herd performance and inbreeding, as well as methods to include un-genotyped animals in such mating programs. A total of 54,535 Holstein-Friesian cattle with imputed high-density genotypes (547,650 SNP after edits) were available. First, to quantify the accuracy of imputing un-genotyped animals (often an issue in populations), a sub-population of 729 genotyped animals had their genotypes masked, and their allele dosages were imputed, using linear regression exploiting information on genotyped relatives. The reference population for imputation included all genotyped animals, excluding the 729 selected animals and their sires, dams, and grandsires, and had either (1) their sires' genotypes, (2) their dams' genotypes (3) both their sires' and their dams' genotypes, or (4) both their sires' and maternal grandsires' genotypes introduced into the reference population. The correlations between true genotypes and the imputed allele dosages ranged from 0.58 (sire only) to 0.68 (both sire and dam). A herd of 100 cows was then simulated (1,000 replicates) from the sub-population of 729 imputed animals. The top 10 bulls from the genotyped population, based on their total genetic merit index (TMI) were selected to be used as sires. Three mating allotment methods were investigated: (1) random mating, (2) sequential mating based on maximizing only the expected TMI of the progeny, and (3) linear programming to maximize a generated index constructed to maximize genetic merit and minimize expected progeny inbreeding as well as intra- and inter-progeny variability in genetic merit. Relationships among candidate parents were calculated using either the pedigree relationship matrix or the genomic relationship matrix; the latter was constructed using either the true genotypes of both parents or the true genotypes of the sire plus the imputed allele dosages of the dam. Using the genomic co-ancestry estimates resulted in lower average herd expected genomic inbreeding levels compared with using the pedigree-based co-ancestry estimates. Additionally, if the dams were not genotyped, using their imputed allele dosages also resulted in lower average herd expected inbreeding levels compared with using the pedigree co-ancestry estimates. The inter-progeny coefficient of variation for selected traits, milk and fertility, estimated breeding values were reduced by 12 to 65% using the linear programing method compared with sequential mating.     

Use of female information in dairy cattle genomic breeding programs

Genomic selection has the potential to increase the accuracy of selection and, therefore, genetic gain, as well as reducing the rate of inbreeding, yet few studies have evaluated the potential benefit of the contribution of females in genomic selection programs. The objective of this study was to determine the effect on genetic gain, accuracy of selection, generation interval, and inbreeding, of including female genotypes in a genomic selection breeding program. A population of approximately 3,500 females and 500 males born annually was simulated and split into an elite and commercial tier representation of the Irish national herd. Several alternative breeding schemes were evaluated to quantify the potential benefit of female genomic information within dairy breeding schemes. Results showed that the inclusion of female phenotypic and genomic information can lead to a 3-fold increase in the rate of genetic gain compared with a traditional BLUP breeding program and decrease the generation interval of the males by 3.8 yr, while maintaining a reasonable rate of inbreeding. The accuracy of the selected males was increased by 73% in the final 3 yr of the genomic schemes compared with the traditional BLUP scheme. The results of this study have several implications for national breeding schemes. Although an investment in genotyping a large population of animals is required, these costs can be offset by the greater genetic gain achievable through the increased accuracy of selection and decreased generation intervals associated with genomic selection.     

Inbreeding in Danish dairy cattle breeds

The purpose of this study was to monitor current and predict future rates of inbreeding in the Danish dairy breeds. Calves born from 1999 until 2003 and registered as Danish Holstein (1,883,983), Danish Jersey (336,966), or Danish Red (261,047) were reference populations. Average complete generation equivalent was approximately 7. For calves born in 2003, average inbreeding was 3.9, 3.4, and 1.4% for Holstein, Jersey, and Danish Red, respectively. In recent years, effective population sizes were 49, 53, and 47, respectively. Based on coancestry statistics, future effective population sizes will be 43, 42, and 51, respectively. The effective number of founders, effective number of ancestors, and effective number of founder genomes were calculated. These measures of genetic diversity were all low for Holstein and Jersey and somewhat larger for Danish Red. The most important ancestors of Danish Holstein were Elevation (13.8%), Chief (10.9%), and Bell (8.5%). The most important ancestor of Danish Red was Momentum (9.4%), a Red Holstein-Friesian. The most important ancestor for Danish Jersey was FYN Lemvig (12.1%) with a large number of progeny in the reference population. The results of this study indicate the necessity for active management of the rate of inbreeding in the future.     

Genomic inbreeding and relationships among Holsteins, Jerseys, and Brown Swiss

Genomic measures of relationship and inbreeding within and across breeds were compared with pedigree measures using genotypes for 43,385 loci of 25,219 Holsteins, 3,068 Jerseys, and 872 Brown Swiss. Adjustment factors allow genomic and pedigree relationships to match more closely within breeds and in multibreed populations and were estimated using means and regressions of genomic on pedigree relationships and allele frequencies in base populations. Correlations of genomic relationships with pedigree inbreeding were higher within each breed when an allele frequency of 0.5, rather than base population frequencies, was used, whereas correlations of average genomic relationships with average pedigree relationships and also reliabilities of genomic evaluations were higher using base population frequencies. Allele frequencies differed in the 3 breeds and were correlated by 0.65 to 0.67 when estimated from genotyped animals compared with 0.72 to 0.74 when estimated from breed base populations. The largest difference in allele frequency was between Holstein and the other breeds on chromosome Bos taurus autosome 4 near a gene affecting appearance of white skin patches (vitiligo) in humans. Each animal's breed composition was predicted very accurately with a standard deviation of <3% using regressions on genotypes at all loci or less accurately with a standard deviation of <6% using subsets of loci. Genomic future inbreeding (half an animal's mean genomic relationship to current animals of the same breed) was correlated by 0.75 to 0.94 with expected future inbreeding (half the average pedigree relationship). Correlations of both were slightly higher with parent averages than with genomic evaluations for net merit of young Holstein bulls. Thus, rates of increase in genomic and pedigree inbreeding per generation should be slightly reduced with genomic selection, in agreement with previous simulations. Genomic inbreeding and future inbreeding have been provided with individual genomic predictions since 2008. New methods to adjust pedigree and genomic relationship matrices so that they match may provide an improved basis for multibreed genomic evaluation. Positive definite matrices can be obtained by adjusting pedigree relationships for covariances among base animals within breed, whereas adjusting genomic relationships to match pedigree relationships can introduce negative eigenvalues. Pedigree relationship matrices ignore common ancestry shared by base animals within breed and may not approximate genomic relationships well in multibreed populations.     

Optimal Genetic Improvement for the High Producing Cow

Many 40,000-lb (18,144 kg) cows exist in today's dairy population, but herds capable of 40,000-lb averages for all cows remain to be developed. Traditional genetic improvement practices, based on consistent use of current high-ranking AI bulls selected to improve economically important traits, will remain important tools to develop high producing cows. Future breeding strategies will likely include attention to how high production is achieved and may include direct selection for increased appetite or some measure of energy balance to support high production, reproduction, and immune function. Direct selection for improved fertility, perhaps involving traits not presently used in herd management, may prove to be necessary as yields increase. Roles for evolving technologies such as marker-assisted selection, manipulation of the bovine genome, and cloning remain unclear, but will likely be incorporated into traditional progeny testing schemes. Equipment to routinely monitor physiological functions may encourage the establishment of large progeny test herds with expanded data recording capability. The expense could lead to proprietary genetic lines and private genetic evaluation systems such as exist in poultry and swine. Pedigree information will become more important in commercial herds to manage inbreeding. The dairy industry can expect to benefit from current research efforts in human genetics. However, current funding of dairy breeding research in the United States will limit the number of individuals trained in methods to implement those results in dairy cattle.     

Inbreeding depression for global and partial economic indexes, production, type, and functional traits

The objective of this research was to examine the effects of inbreeding in the population of Holstein cattle in the Walloon region of Belgium. The effects of inbreeding on the global economic index and its components were studied by using data from the genetic evaluations of February 2004 for production, somatic cell score (SCS), computed from somatic cell counts and type. Inbreeding coefficients for 956,516 animals were computed using a method that allows assigning an inbreeding coefficient to individuals without known parents. These coefficients were equal to the mean inbreeding coefficient of contemporary individuals with known parents. The significance of inbreeding effects on the different evaluated traits and on the different indexes were tested using a t-test comparing estimated standard errors and effects. The inbreeding effect was significantly different from zero for the vast majority of evaluated traits and for all of the indexes. Inbreeding had the greatest deleterious effects on production traits. Inbreeding decreased yield of milk, fat, and protein during a lactation by 19.68, 0.96, and 0.69 kg, respectively, per each 1% increase in inbreeding. The regression coefficient of SCS per 1% increase in inbreeding was +0.005 SCS units. The inbreeding depression was thus relatively low for SCS, but inbred animals had higher SCS than non-inbred animals, indicating that inbred animals would be slightly more sensitive to mastitis than non-inbred animals. Estimates of inbreeding effects on evaluated type traits per 1% increase were small. The most strongly affected type traits were chest width, rear leg, and overall development on a standardized scale. For several type traits, particularly traits linked to the udder, the estimates suggested a favorable effect of inbreeding. The global economic index was depressed by around 6.13 € of lifetime profit per 1% increase in inbreeding for the Holstein animals in the Walloon region of Belgium.     

Uncontrolled Inbreeding

The main objective of this review is provide a general overview of the current inbreeding status in major livestock types and to remind all animal breeders that increasing accuracy and intensity of selection are not the only considerations in a genetic improvement program. A second objective is to set the stage for detailed reviews of the situations in some individual species in this symposium. Intense selection in livestock without careful mating and large effective population size has led to uncontrolled inbreeding in many species. Modern and likely future genetic techniques will probably increase this trend unless steps to alleviate it are taken. Without control of inbreeding, deterioration in lowly heritable but economically important traits such as reproductive efficiency and survival is likely. All breeds and breeders in all species should take steps to reduce uncontrolled inbreeding to maintain genetic variation and improve competitiveness with other food protein sources.     

Ex situ conservation of Holstein-Friesian cattle: comparing the Dutch, French, and US germplasm collections

Holstein-Friesian (HF) gene bank collections were established in France, the Netherlands, and the United States to conserve genetic diversity for this breed. Genetic diversity of HF collections within and between countries was assessed and compared with active male HF populations in each country by using pedigree data. Measures of genetic diversity such as probability of gene origin inbreeding and kinship were calculated. The cryobanks have captured substantial amounts of genetic diversity for the HF compared with the current populations. A substantial part of the US, French, and Dutch collections seems to be genetically similar. On the other hand, the US collection in particular represents an interesting reservoir of HF genes of the past. Gene banks can play an important role in conserving genetic diversity within livestock breeds over time, and may support industry in the future when needed.     

A comparison of dairy cattle breeding designs that use genomic selection

Different dairy cattle breeding schemes were compared using stochastic simulations, in which the accuracy of the genomic breeding values was dependent on the structure of the breeding scheme, through the availability of new genotyped animals with phenotypic information. Most studies that predict the gain by implementing genomic selection apply a deterministic approach that requires assumptions about the accuracy of the genomic breeding values. The achieved genetic gain, when genomic selection was the only selection method to directly identify elite sires for widespread use and progeny testing was omitted, was compared with using genomic selection for preselection of young bulls for progeny testing and to a conventional progeny test scheme. The rate of inbreeding could be reduced by selecting more sires every year. Selecting 20 sires directly on their genomic breeding values gave a higher genetic gain than any progeny testing scheme, with the same rate of inbreeding as the schemes that used genomic selection for preselection of bulls before progeny testing. The genomic selection breeding schemes could reduce the rate of inbreeding and still increase genetic gain, compared with the conventional breeding scheme. Since progeny testing is expensive, the breeding scheme omitting the progeny test will be the cheapest one. Keeping the progeny test and use of genomic selection for preselection still has some advantages. It gives higher accuracy of breeding values and does not require a complete restructuring of the breeding program. Comparing at the same rate of inbreeding, using genomic selection for elite sire selection only gives a 13% increase in genetic gain, compared with using genomic selection for preselection. One way to reduce the costs of the scheme where genomic selection was used for preselection is to reduce the number of progeny tested bulls. This was here achieved without getting lower genetic gain or a higher rate of inbreeding.     

Genome-wide mapping and estimation of inbreeding depression of semen quality traits in a cattle population

Inbreeding depression is known to affect quantitative traits such as male fertility and sperm quality, but the genetic basis for these associations is poorly understood. Most studies have been limited to examining how pedigree- or marker-derived genome-wide autozygosity is associated with quantitative phenotypes. In this study, we analyzed possible associations of genetic features of inbreeding depression with percentage of live spermatozoa and total number of spermatozoa in 19,720 ejaculates obtained from 554 Austrian Fleckvieh bulls during routine artificial insemination programs. Genome-wide inbreeding depression was estimated and genomic regions contributing to inbreeding depression were mapped. Inbreeding depression did affect total number of spermatozoa, and such depression was predicted by pedigree-based inbreeding levels and genome-wide inbreeding levels based on runs of homozygosity (ROH). Genome-wide inbreeding depression did not seem to affect percentage of live spermatozoa. A model incorporating genetic effects of the bull, environmental factors, and additive genetic and ROH status effects of individual single-nucleotide polymorphisms revealed genomic regions significantly associated with ROH status for total number of spermatozoa (4 regions) or percentage of live spermatozoa (5 regions). All but one region contains genes related to spermatogenesis and sperm morphology. These genomic regions contain genes affecting sperm morphogenesis and efficacy. The results highlight that next-generation sequencing may help explain some of the genetic factors contributing to inbreeding depression of sperm quality traits in Fleckvieh bulls.     

Effects of genomic selection on genetic improvement, inbreeding, and merit of young versus proven bulls

Genomic selection has the potential to revolutionize dairy cattle breeding because young animals can be accurately selected as parents, leading to a much shorter generation interval and higher rates of genetic gain. The aims of this study were to assess the effects of genomic selection and reduction of the generation interval on the rate of genetic gain and rate of inbreeding. Furthermore, the merit of proven bulls relative to young bulls was studied. This is important for breeding organizations as it determines the relative importance of progeny testing. A closed nucleus breeding scheme was simulated in which 1,000 males and 1,000 females were born annually, 200 bulls were progeny tested, and 20 sires and 200 dams were selected to produce the next generation. In the “proven” (PROV) scenario, only cows with own performance records and progeny-tested bulls were selected as parents. The proportion of the genetic variance that was explained by simulated marker information (M) was varied from 0 to 100%. When M increased from 0 to 100%, the rate of genetic gain increased from 0.238 to 0.309 genetic standard deviations (σ) per year (+30%), whereas the rate of inbreeding reduced from 1.00 to 0.42% per generation. Alternatively, when young cows and bulls were selected as parents (YNG scenario), the rate of genetic gain for M = 0% was 0.292 σ/yr but the corresponding rate of inbreeding increased substantially to 3.15% per generation. A realistic genomic selection scheme (YNG with M = 40%) gave 108% higher rate of genetic gain (0.495 σ/yr) and approximately the same rate of inbreeding per generation as the conventional system without genomic selection (PROV with M = 0%). The rate of inbreeding per year, however, increased from 0.18 to 0.52% because the generation interval in the YNG scheme was much shorter. Progeny-testing fewer bulls reduced the rate of genetic gain and increased the rate of inbreeding for PROV, but had negligible effects for YNG because almost all sires were young bulls. In scenario YNG with M = 40%, the best young bulls were superior to the best proven bulls by 1.27 σ difference in genomic estimated breeding value. This superiority increased even further when fewer bulls were progeny tested. This stochastic simulation study shows that genomic selection in combination with a severe reduction in the generation interval can double the rate of genetic gain at the same rate of inbreeding per generation, but with a higher rate of inbreeding per year. The number of progeny-tested bulls can be greatly reduced, although this will slightly affect the quality of the proven bull team. Therefore, it is important for breeding organizations to predict the future demand for proven bull semen in light of the increasing superiority of young bulls.     

Novel strategies to minimize progeny inbreeding while maximizing genetic gain using genomic information

In this study, 3 strategies for controlling progeny inbreeding in mating plans were compared. The strategies used information from pedigree inbreeding coefficients, genomic relationships, or shared runs of homozygosity. The strategies were compared for the reduction in genetic gain and progeny inbreeding that would be expected from selected matings, and for the decrease of homozygosity of deleterious recessive alleles. Using real pedigree, genotype [43,115 single nucleotide polymorphism (SNP) markers], and estimated breeding value data from Holstein cattle, mating plans were derived for herds of 300 cows with 20 sires available for mating, replicated 50 times. Each of the 300 individuals allocated as dams were matched to 1 of 20 sires to maximize genetic merit minus the penalty for estimated progeny inbreeding, and given the restriction that the sire could not be mated to more than 10% of the cows. The strategy that used a genomic relationship matrix (GRM) was the most effective in reducing average progeny inbreeding; this strategy also resulted in fewer homozygous SNP out of 1,000 low-frequency SNP compared with the strategy using pedigree information. In the future, large numbers of cattle may be genotyped for low-density SNP panels. A GRM constructed using 3,123 SNP produced results similar to a GRM constructed using the full 43,115 SNP. These results demonstrate that using GRM information, a 1% reduction in progeny inbreeding (valued at around $5 per cow) can be made with very little compromise in the overall breeding objective. These results and the availability of low-cost, low-density genotyping make it attractive to apply mating plans that use genomic information in commercial dairy herds.