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Egg quality is a vital factor in the poultry industry. High-quality eggs not only meet consumer expectations for appearance, taste, and nutritional value but also have high marketability, profitability, and consumer satisfaction. Accordingly, we executed our research with the purpose of determining chromosomal regions and genetic markers associated with egg quality in an F2 cross-bred chicken population under tropical conditions; we determined these through a genome-wide association study and quantitative trait locus (QTL) mapping. This population was created by cross-breeding the L2 line of Taiwan Country chickens, which is adapted to local conditions in Taiwan, with an experimental line (R-line) of Rhode Island Red layer chickens, which was developed by the French National Research Institute for Agriculture, Food and the Environment. A 60 K single nucleotide polymorphism (SNP) genotyping array for chickens was employed to execute the analysis. Our analysis revealed 40 QTLs associated with egg quality under tropical conditions, namely 20 QTLs with genome-wide statistical significance and 20 QTLs with chromosome-wide statistical significance. Furthermore, we identified 93 SNPs exerting discernible effects on egg quality, with 10 of these effects exhibiting genome-wide significance and 83 exhibiting potential significance. The majority of the detected QTL regions and SNPs agreed with those identified as having an association with egg quality or production traits in previous studies, thus supporting the interrelationships determined between the studied characteristics. The findings of this study enhance the understanding regarding the genetic regulation governing chicken egg quality, thereby serving as a valuable reference for future functional investigations., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The common cattle tick Rhipicephalus microplus causes severe limitations to livestock production. Bovine genetics could be a decisive component for the success or failure of control programs for ticks and diseases transmitted. The objective of this work was to detect chromosomal regions associated with host resistance to R. microplus through an associative mapping study using medium and high density microarrays in a population of Argentine Creole cattle. The phenotypic record of the number of ticks that completed their development on the host, after artificial infestations, was obtained during 2015 to 2020. Genomic DNA was extracted for genotyping from 192 animals using Affymetrix high (Axiom™ Bos 1) and medium density (ArBos1) microarrays. In an exploratory study, chromosomal regions containing putative quantitative trait loci (QTLs) were recognized on chromosomes 27, 11, 10, 9, 16, 13, 3, 19, 8 and 18, associated with the variation of R. microplus load. Gene ontology based on genes located on these regions revealed an enrichment of terms and pathways for the immune system, blood coagulation, tissue regeneration, endopeptidase activity and protein phosphorylation. The information obtained in this work constitutes a first report of QTLs for tick count in the Argentine Creole cattle, and contributes with the knowledge about the underlying process involved in tick resistance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

1. 'Congenital loco' is a disorder in birds expressed at hatching, and the primary symptom is dorsal backward bending of the neck. It is a recessive disease caused by a mutation in a specific genetic locus. The following study identified a novel locus associated with congenital loco in Silkie Fowl chickens.2. Normal and congenital loco-affected Silkie Fowl chicks exhibited no differences in the frequencies of markers on chromosome 12 adjacent to the congenital loco locus reported in a previous study in Rhode Island Red chickens. Sex determination of congenital loco-affected chicks revealed that they were female only.3. Bulked segregant analyses using next-generation sequencing narrowed the causative region of congenital loco to approximately 3.3 Mb between bases 9,569,012 and 12,863,792 on chromosome Z.

Random samples from generation S 41 of the Virginia high and low 8-week body weight lines formed the base population for producing a multigenerational reciprocal intercross population. Although genetic mapping from this intercross has been reported, lacking are phenotypic trends across multiple generations. Here, we provide phenotypic information for the parental base population, the F 1 reciprocal cross, and subsequent segregating recombinant generations F 2 to F 17 . Heterosis for the selected trait in the F 1 was negative for both reciprocal crosses. Phenotypic correlations for the selected trait in the recombinant generations were essentially nil for both males and females as was percent sexual dimorphism and coefficients of variation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Understanding the genetic mechanisms that underlie innate fear behavior is essential for improving the management and performance of the poultry industry. This study aimed to map QTL associated with innate fear responses in open field (OF) and tonic immobility (TI) tests, using an F2 chicken intercross population between 2 behaviorally distinct breeds: the aggressive Japanese Oh-Shamo (OSM) and the docile White Leghorn T-line (WL-T). Genome-wide QTL analysis for the OF and TI traits was conducted using 2,109 single nucleotide polymorphism (SNP) markers obtained through restriction site-associated DNA sequencing (RAD-seq). While several suggestive QTL were identified for TI and OF traits at genome-wide 20% significance threshold levels, the analysis revealed 2 significant QTL for 2 OF traits (total distance and maximum speed) at genome-wide 5% significance threshold levels. These significant QTL were located between 12.34 and 30.49 megabase (Mb) on chromosome 1 and between 40.02 and 63.38 Mb on chromosome 2, explaining 6.75 to 7.40% of the total variances. These findings provide valuable insights for the poultry industry, particularly in refining chicken management strategies and informing targeted breeding efforts., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Genetic dissection of highly polygenic traits is a challenge, in part due to the power necessary to confidently identify loci with minor effects. Experimental crosses are valuable resources for mapping such traits. Traditionally, genome-wide analyses of experimental crosses have targeted major loci using data from a single generation (often the F 2 ) with individuals from later generations being generated for replication and fine-mapping. Here, we aim to confidently identify minor-effect loci contributing to the highly polygenic basis of the long-term, bi-directional selection responses for 56-d body weight in the Virginia body weight chicken lines. To achieve this, a strategy was developed to make use of data from all generations (F 2 -F 18 ) of the advanced intercross line, developed by crossing the low and high selected lines after 40 generations of selection. A cost-efficient low-coverage sequencing based approach was used to obtain high-confidence genotypes in 1Mb bins across 99.3% of the chicken genome for >3,300 intercross individuals. In total, 12 genome-wide significant, and 30 additional suggestive QTL reaching a 10% FDR threshold, were mapped for 56-d body weight. Only 2 of these QTL reached genome-wide significance in earlier analyses of the F 2 generation. The minor-effect QTL mapped here were generally due to an overall increase in power by integrating data across generations, with contributions from increased genome-coverage and improved marker information content. The 12 significant QTL explain >37% of the difference between the parental lines, three times more than 2 previously reported significant QTL. The 42 significant and suggestive QTL together explain >80%. Making integrated use of all available samples from multiple generations in experimental crosses are economically feasible using the low-cost, sequencing-based genotyping strategies outlined here. Our empirical results illustrate the value of this strategy for mapping novel minor-effect loci contributing to complex traits to provide a more confident, comprehensive view of the individual loci that form the genetic basis of the highly polygenic, long-term selection responses for 56-d body weight in the Virginia body weight chicken lines., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Meiotic recombination is an important evolutionary mechanism that breaks up linkages between loci and creates novel haplotypes for selection to act upon. Understanding the genetic control of variation in recombination rates is therefore of great interest in both natural and domestic breeding populations. In this study, we used pedigree information and medium-density (∼50K) genotyped data in a large cattle (Bos taurus) breeding population in Norway (Norwegian Red cattle) to investigate recombination rate variation between sexes and individual animals. Sex-specific linkage mapping showed higher rates in males than in females (total genetic length of autosomes = 2,492.9 cM in males and 2,308.9 cM in females). However, distribution of recombination along the genome showed little variation between males and females compared with that in other species. The heritability of autosomal crossover count was low but significant in both sexes (h 2 = 0.04 and 0.09 in males and females, respectively). We identified 2 loci associated with variation in individual crossover counts in female, one close to the candidate gene CEP55 and one close to both MLH3 and NEK9. All 3 genes have been associated with recombination rates in other cattle breeds. Our study contributes to the understanding of how recombination rates are controlled and how they may vary between closely related breeds as well as between species., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The onset of lactation results in a sudden irreversible loss of Ca for colostrum and milk synthesis. Some cows are unable to quickly adapt to this demand and succumb to clinical hypocalcemia, whereas a larger proportion of cows develop subclinical hypocalcemia that predisposes them to other peripartum diseases. The objective of this study was to perform a comprehensive genomic analysis of blood total Ca concentration in periparturient Holstein cows. We first performed a genomic scan and a subsequent gene-set analysis to identify candidate genes, biological pathways, and molecular mechanisms affecting postpartum Ca concentration. Then, we assessed the prediction of postpartum Ca concentration using genomic information. Data consisted of 7,691 records of plasma or serum concentrations of Ca measured in the first, second, and third day after parturition of 959 primiparous and 1,615 multiparous cows that calved between December 2015 and June 2020 in 2 dairy herds. All cows were genotyped with 80k SNPs. The statistical model included lactation (1 to 5+), calf category (male, females, twins), and day as fixed effects, and season-treatment-experiment, animal, and permanent environmental as random effects. Model predictive ability was evaluated using 10-fold cross-validation. Heritability and repeatability estimates were 0.083 (standard error = 0.017) and 0.444 (standard error = 0.028). The association mapping identified 2 major regions located on Bos taurus autosome (BTA)6 and BTA16 that explained 1.2% and 0.7% of additive genetic variance of Ca concentration, respectively. Interestingly, the region on BTA6 harbors the GC gene, which encodes the vitamin D binding protein, and the region on BTA16 harbors LRRC38, which is actively involved in K transport. Other sizable peaks were identified on BTA5, BTA2, BTA7, BTA14, and BTA9. These regions harbor genes associated with Ca channels (CACNA1S, CRACR2A), K channels (KCNK9), bone remodeling (LRP6), and milk production (SOCS2). The gene-set analysis revealed terms related to vitamin transport, calcium ion transport, calcium ion binding, and calcium signaling. Genomic predictions of phenotypic and genomic estimated breeding values of Ca concentration yielded predictive correlations up to 0.50 and 0.15, respectively. Overall, the present study contributes to a better understanding of the genetic basis of postpartum blood Ca concentration in Holstein cows. In addition, the findings may contribute to the development of novel selection and management strategies for reducing periparturient hypocalcemia in dairy cattle., (© 2022, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

While understanding the genetic basis of heat tolerance is crucial in the context of global warming's effect on humans, livestock, and wildlife, the specific genetic variants and biological features that confer thermotolerance in animals are still not well characterized. We used dairy cows as a model to study heat tolerance because they are lactating, and therefore often prone to thermal stress. The data comprised almost 0.5 million milk records (milk, fat, and proteins) of 29,107 Australian Holsteins, each having around 15 million imputed sequence variants. Dairy animals often reduce their milk production when temperature and humidity rise; thus, the phenotypes used to measure an individual's heat tolerance were defined as the rate of milk production decline (slope traits) with a rising temperature-humidity index. With these slope traits, we performed a genome-wide association study (GWAS) using different approaches, including conditional analyses, to correct for the relationship between heat tolerance and level of milk production. The results revealed multiple novel loci for heat tolerance, including 61 potential functional variants at sites highly conserved across 100 vertebrate species. Moreover, it was interesting that specific candidate variants and genes are related to the neuronal system (ITPR1, ITPR2, and GRIA4) and neuroactive ligand-receptor interaction functions for heat tolerance (NPFFR2, CALCR, and GHR), providing a novel insight that can help to develop genetic and management approaches to combat heat stress., (© 2021. The Author(s).)

Meat from Korean native chickens (KNCs) has high consumer demand; however, slow growth performance and high variation in body weight (BW) of KNCs remain an issue. Genome-wide association study (GWAS) is a powerful method to identify quantitative trait-associated genomic loci. A GWAS, based on a large-scale KNC population, is needed to identify underlying genetic mechanisms related to its growth traits. To identify BW-associated genomic regions, we performed a GWAS using the chicken 60K single nucleotide polymorphism (SNP) panel for 1328 KNCs. BW was measured at 8 weeks of age, from 2018 to 2020. Twelve SNPs were associated with BW at the suggestive significance level ( p < 2.95 × 10 -5 ) and located near or within 11 candidate genes, including WDR37 , KCNIP4 , SLIT2 , PPARGC1A , MYOCD and ADGRA3 . Gene set enrichment analysis based on the GWAS results at p < 0.05 (1680 SNPs) showed that 32 Gene Ontology terms and two Kyoto Encyclopedia of Genes and Genomes pathways, including regulation of transcription, motor activity, the mitogen-activated protein kinase signaling pathway, and tight junction, were significantly enriched ( p < 0.05) for BW-associated genes. These pathways are involved in cell growth and development, related to BW gain. The identified SNPs are potential biomarkers in KNC breeding.

Chinese perch, Siniperca chuatsi (Basilewsky), is one of the most commercially important cultured fishes in China. In the present study, a high-density genetic linkage map of Chinese perch was constructed by genotyping-by-sequencing technique with an F1 mapping panel containing 190 progenies. A total of 2328 SNPs were assigned to 24 linkage groups (LGs), agreeing with the chromosome haploid number in this species (n = 24). The sex-averaged map covered 97.9% of the Chinese perch genome, with the length of 1694.3 cM and a marker density of 0.7 cM/locus. The number of markers per LG ranged from 57 to 222, with a mean of 97. The length of LGs varied from 43.2 to 108.2 cM, with a mean size of 70.6 cM. The recombination rate of females was 1.5:1, which was higher than that of males. To better understand the distribution pattern of segregation distortion between the two sexes of Chinese perch, the skewed markers were retained and used to reconstruct the sex-specific maps. The 16 segregation distortion regions were identified on 10 LGs of the female map, while 12 segregation distortion regions on eight LGs of the male map. Among these LGs, six LGs matched between the sex-specific maps. This high-density linkage map could provide a solid basis for identifying QTL associated with economically important traits, and for implementing marker-assisted selection breeding of Chinese perch., (© 2021 Stichting International Foundation for Animal Genetics.)

A large F2 cross with 920 Japanese quail was used to map QTL for phosphorus utilization, calcium utilization, feed per gain and body weight gain. In addition, four bone ash traits were included, because it is known that they are genetically correlated with the focal trait of phosphorus utilization. Trait recording was done at the juvenile stage of the birds. The individuals were genotyped genome-wide for about 4k SNPs and a linkage map constructed, which agreed well with the reference genome. QTL linkage mapping was performed using multimarker regression analysis in a line cross model. Single marker association mapping was done within the mapped QTL regions. The results revealed several genome-wide significant QTL. For the focal trait phosphorus utilization, a QTL on chromosome CJA3 could be detected by linkage mapping, which was substantiated by the results of the SNP association mapping. Four candidate genes were identified for this QTL, which should be investigated in future functional studies. Some overlap of QTL regions for different traits was detected, which is in agreement with the corresponding genetic correlations. It seems that all traits investigated are polygenic in nature with some significant QTL and probably many other small-effect QTL that were not detectable in this study., (© 2020 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.)

The enhanced availability of sequence data in livestock provides an opportunity for more accurate predictions in routine genomic evaluations. Such evaluations would therefore no longer rely only on the linkage disequilibrium between a chip marker and the causal mutation. The objective of this study was to assess the usefulness of sequence data in Saanen goats (n = 33) to better capture a quantitative trait locus (QTL) on chromosome 19 (CHI19) and improve the accuracy of predictions for 3 milk production traits, 5 type traits, and somatic cell scores. All 1,207 50K genotypes were imputed to the sequence level. Four scenarios, each using a subset of CHI19 imputed variants, were then tested. Sequence-derived information included all CHI19 variants (529,576), all variants in the QTL region (22,269), 178 variants selected in the QTL region and added to an updated chip, or 178 randomly selected variants on CHI19. Two genomic evaluation models were applied: single-step genomic BLUP and weighted single-step genomic BLUP. All scenarios were compared with single-step genomic BLUP using 50K genotypes. Best overall results were obtained using single-step genomic BLUP on 50K genotypes completed with all variants in the QTL region of chromosome 19 (6.2% average increase in accuracy for 9 traits) with the highest accuracy gain for fat yield (17.9%), significant increases for milk (13.7%) and protein yields (12.5%), and type traits associated with CHI19. Despite its association with the QTL region of chromosome 19, the somatic cell score showed decreased accuracy in every alternative scenario. Using all CHI19 variants led to an overall decrease of 4.8% in prediction accuracy. The updated chip was efficient and improved genomic evaluations by 3.1 to 6.4% on average, depending on the scenario. Indeed, information from only a few carefully selected variants increased accuracies for traits of interest when used in a single-step genomic BLUP model. In conclusion, using QTL region variants imputed from sequence data in single-step genomic evaluations represents a promising perspective for such evaluations in dairy goats. Furthermore, using only a limited number of selected variants in QTL regions, as available on SNP chip updates, significantly increases the accuracy for QTL-associated traits without deteriorating the evaluation accuracy for other traits. The latter approach is interesting, as it avoids time-consuming imputation and data formatting processes and provides reliable genotypes., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Sow fertility traits, such as litter size and the number of lifetime parities produced (reproductive longevity), are economically important. Selection for these traits is difficult because they are lowly heritable and expressed late in life. Age at puberty (AP) is an early indicator of reproductive longevity. Here, we utilized a custom Affymetrix single-nucleotide polymorphisms (SNPs) array (SowPro90) enriched with positional candidate genetic variants for AP and a haplotype-based genome-wide association study to fine map the genetic sources associated with AP and other fertility traits in research (University of Nebraska-Lincoln [UNL]) and commercial sow populations. Five major quantitative trait loci (QTL) located on four Sus scrofa chromosomes (SSC2, SSC7, SSC14, and SSC18) were discovered for AP in the UNL population. Negative correlations (r = -0.96 to -0.10; P < 0.0001) were observed at each QTL between genomic estimated breeding values for AP and reproductive longevity measured as lifetime number of parities (LTNP). Some of the SNPs discovered in the major QTL regions for AP were located in candidate genes with fertility-associated gene ontologies (e.g., P2RX3, NR2F2, OAS1, and PTPN11). These SNPs showed significant (P < 0.05) or suggestive (P < 0.15) associations with AP, reproductive longevity, and litter size traits in the UNL population and litter size traits in the commercial sows. For example, in the UNL population, when the number of favorable alleles of an SNP located in the 3' untranslated region of PTPN11 (SSC14) increased, AP decreased (P < 0.0001), while LTNP increased (P < 0.10). Additionally, a suggestive difference in the observed NR2F2 isoforms usage was hypothesized to be the source of the QTL for puberty onset mapped on SSC7. It will be beneficial to further characterize these candidate SNPs and genes to understand their impact on protein sequence and function, gene expression, splicing process, and how these changes affect the phenotypic variation of fertility traits., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Marek's disease (MD) represents a significant global economic and animal welfare issue. Marek's disease virus (MDV) is a highly contagious oncogenic and highly immune-suppressive α-herpes virus, which infects chickens, causing neurological effects and tumour formation. Though partially controlled by vaccination, MD continues to have a profound impact on animal health and on the poultry industry. Genetic selection provides an alternative and complementary method to vaccination. However, even after years of study, the genetic mechanisms underlying resistance to MDV remain poorly understood. The Major Histocompatability Complex (MHC) is known to play a role in disease resistance, along with a handful of other non-MHC genes. In this study, one of the largest to date, we used a multi-facetted approach to identify QTL regions (QTLR) influencing resistance to MDV, including an F 6 population from a full-sib advanced intercross line (FSIL) between two elite commercial layer lines differing in resistance to MDV, RNA-seq information from virus challenged chicks, and genome wide association study (GWAS) from multiple commercial lines. Candidate genomic elements residing in the QTLR were further tested for association with offspring mortality in the face of MDV challenge in eight pure lines of elite egg-layer birds. Thirty-eight QTLR were found on 19 chicken chromosomes. Candidate genes, miRNAs, lncRNAs and potentially functional mutations were identified in these regions. Association tests were carried out in 26 of the QTLR, using eight pure lines of elite egg-layer birds. Numerous candidate genomic elements were strongly associated with MD resistance. Genomic regions significantly associated with resistance to MDV were mapped and candidate genes identified. Various QTLR elements were shown to have a strong genetic association with resistance. These results provide a large number of significant targets for mitigating the effects of MDV infection on both poultry health and the economy, whether by means of selective breeding, improved vaccine design, or gene-editing technologies.

Background: Single nucleotide polymorphisms (SNPs) which capture a significant impact on a trait can be identified with genome-wide association studies. High linkage disequilibrium (LD) among SNPs makes it difficult to identify causative variants correctly. Thus, often target regions instead of single SNPs are reported. Sample size has not only a crucial impact on the precision of parameter estimates, it also ensures that a desired level of statistical power can be reached. We study the design of experiments for fine-mapping of signals of a quantitative trait locus in such a target region., Methods: A multi-locus model allows to identify causative variants simultaneously, to state their positions more precisely and to account for existing dependencies. Based on the commonly applied SNP-BLUP approach, we determine the z-score statistic for locally testing non-zero SNP effects and investigate its distribution under the alternative hypothesis. This quantity employs the theoretical instead of observed dependence between SNPs; it can be set up as a function of paternal and maternal LD for any given population structure., Results: We simulated multiple paternal half-sib families and considered a target region of 1 Mbp. A bimodal distribution of estimated sample size was observed, particularly if more than two causative variants were assumed. The median of estimates constituted the final proposal of optimal sample size; it was consistently less than sample size estimated from single-SNP investigation which was used as a baseline approach. The second mode pointed to inflated sample sizes and could be explained by blocks of varying linkage phases leading to negative correlations between SNPs. Optimal sample size increased almost linearly with number of signals to be identified but depended much stronger on the assumption on heritability. For instance, three times as many samples were required if heritability was 0.1 compared to 0.3. An R package is provided that comprises all required tools., Conclusions: Our approach incorporates information about the population structure into the design of experiments. Compared to a conventional method, this leads to a reduced estimate of sample size enabling the resource-saving design of future experiments for fine-mapping of candidate variants.

In order to map quantitative trait loci (QTLs) for allometries of body compositions and metabolic traits in chicken, we phenotypically characterize the allometric growths of multiple body components and metabolic traits relative to BWs using joint allometric scaling models and then establish random regression models (RRMs) to fit genetic effects of markers and minor polygenes derived from the pedigree on the allometric scalings. Prior to statistically inferring the QTLs for the allometric scalings by solving the RRMs, the LASSO technique is adopted to rapidly shrink most of marker genetic effects to zero. Computer simulation analysis confirms the reliability and adaptability of the so-called LASSO-RRM mapping method. In the F2 population constructed by multiple families, we formulate two joint allometric scaling models of body compositions and metabolic traits, in which six of nine body compositions are tested as significant, while six of eight metabolic traits are as significant. For body compositions, a total of 14 QTLs, of which 9 dominant, were detected to be associated with the allometric scalings of drumstick, fat, heart, shank, liver and spleen to BWs; while for metabolic traits, a total of 19 QTLs also including 9 dominant be responsible for the allometries of T4, IGFI, IGFII, GLC, INS, IGR to BWs. The detectable QTLs or highly linked markers can be used to regulate relative growths of the body components and metabolic traits to BWs in marker-assisted breeding of chickens.

The pulmonary hypoplasia and anasarca syndrome (PHA) is a congenital lethal disorder, which until now has been reported in cattle and sheep. PHA is characterized by extensive subcutaneous fetal edema combined with hypoplasia or aplasia of the lungs and dysplasia of the lymphatic system. PHA is assumed to be of genetic etiology. This study presents the occurrence of PHA in two different cattle breeds and their genetic causation. Two PHA cases from one sire were observed in Slovenian Cika cattle. Under the assumption of monogenic inheritance, genome-wide homozygosity mapping scaled down the critical regions to 3% of the bovine genome including a 43.6 Mb-sized segment on chromosome 6. Whole-genome sequencing of one case, variant filtering against controls and genotyping of a larger cohort of Cika cattle led to the detection of a likely pathogenic protein-changing variant perfectly associated with the disease: a missense variant on chromosome 6 in ADAMTS3 (NM&#95;001192797.1: c.1222C>T), which affects an evolutionary conserved residue (NP&#95;001179726.1: p.(His408Tyr)). A single PHA case was found in Danish Holstein cattle and was whole-genome sequenced along with its parents. However, as there was no plausible private protein-changing variant, mining for structural variation revealed a likely pathogenic trisomy of the entire chromosome 20. The identified ADAMTS3 associated missense variant and the trisomy 20 are two different genetic causes, which shows a compelling genetic heterogeneity for bovine PHA., (© 2020 Stichting International Foundation for Animal Genetics.)

The rhesus macaque is an abundant species of Old World monkeys and a valuable model organism for biomedical research due to its close phylogenetic relationship to humans. Copy number variation is one of the main sources of genomic diversity within and between species and a widely recognized cause of inter-individual differences in disease risk. However, copy number differences among rhesus macaques and between the human and macaque genomes, as well as the relevance of this diversity to research involving this nonhuman primate, remain understudied. Here we present a high-resolution map of sequence copy number for the rhesus macaque genome constructed from a dataset of 198 individuals. Our results show that about one-eighth of the rhesus macaque reference genome is composed of recently duplicated regions, either copy number variable regions or fixed duplications. Comparison with human genomic copy number maps based on previously published data shows that, despite overall similarities in the genome-wide distribution of these regions, there are specific differences at the chromosome level. Some of these create differences in the copy number profile between human disease genes and their rhesus macaque orthologs. Our results highlight the importance of addressing the number of copies of target genes in the design of experiments and cautions against human-centered assumptions in research conducted with model organisms. Overall, we present a genome-wide copy number map from a large sample of rhesus macaque individuals representing an important novel contribution concerning the evolution of copy number in primate genomes., Competing Interests: The authors have declared that no competing interests exist.

Alpaca is a camelid species of broad economic, biological and biomedical interest, and an essential part of the cultural and historical heritage of Peru. Recently, efforts have been made to improve knowledge of the alpaca genome, and its genetics and cytogenetics, to develop molecular tools for selection and breeding. Here, we report cytogenetic mapping of 35 new markers to 19 alpaca autosomes and the X chromosome. Twenty-eight markers represent alpaca SNPs, of which 17 are located inside or near protein-coding genes, two are in ncRNA genes and nine are intergenic. The remaining seven markers correspond to candidate genes for fiber characteristics ( BMP4, COL1A2, GLI1, SFRP4) , coat color ( TYR ) and development ( CHD7, PAX7 ). The results take the tally of cytogenetically mapped markers in alpaca to 281, covering all 36 autosomes and the sex chromosomes. The new map assignments overall agree with human-camelid conserved synteny data, except for mapping BMP4 to VPA3, suggesting a hitherto unknown homology with HSA14. The findings validate, refine and correct the current alpaca assembly VicPac3.1 by anchoring unassigned sequence scaffolds, and ordering and orienting assigned scaffolds. The study contributes to the improvement in the alpaca reference genome and advances camelid molecular cytogenetics.

Background: More teats are necessary for sows to nurse larger litters to provide immunity and nutrient for piglets prior to weaning. Previous studies have reported the strong effect of an insertion mutation in the Vertebrae Development Associated (VRTN) gene on Sus scrofa chromosome 7 (SSC7) that increased the number of thoracic vertebrae and teat number in pigs. We used genome-wide association studies (GWAS) to map genetic markers and genes associated with teat number in two Duroc pig populations with different genetic backgrounds. A single marker method and several multi-locus methods were utilized. A meta-analysis that combined the effects and P-values of 34,681 single nucleotide polymorphisms (SNPs) that were common in the results of single marker GWAS of American and Canadian Duroc pigs was conducted. We also performed association tests between the VRTN insertion and teat number in the same populations., Results: A total of 97 SNPs were found to be associated with teat number. Among these, six, eight and seven SNPs were consistently detected with two, three and four multi-locus methods, respectively. Seven SNPs were concordantly identified between single marker and multi-locus methods. Moreover, 26 SNPs were newly found by multi-locus methods to be associated with teat number. Notably, we detected one consistent quantitative trait locus (QTL) on SSC7 for teat number using single-locus and meta-analysis of GWAS and the top SNP (rs692640845) explained 8.68% phenotypic variance of teat number in the Canadian Duroc pigs. The associations between the VRTN insertion and teat number in two Duroc pig populations were substantially weaker. Further analysis revealed that the effect of VRTN on teat number may be mediated by its LD with the true causal mutation., Conclusions: Our study suggested that VRTN insertion may not be a strong or the only candidate causal mutation for the QTL on SSC7 for teat number in the analyzed Duroc pig populations. The combination of single-locus and multi-locus GWAS detected additional SNPs that were absent using only one model. The identified SNPs will be useful for the genetic improvement of teat number in pigs by assigning higher weights to associated SNPs in genomic selection.

Background: Achieving rapid genetic progress while maintaining adequate genetic diversity is one of the main challenges facing the dairy industry. The increase in inbreeding can be used to monitor the loss of genetic diversity. Inbreeding tends to increase the proportion of homozygous loci, some of which cause homozygosity of recessive alleles that results in reduced performance. This phenomenon is known as inbreeding depression and tends to be most prominent on fitness-related traits, such as male fertility. Traditionally, inbreeding has been monitored using pedigree information, or more recently, genomic data. Alternatively, it can be quantified using runs of homozygosity (ROH), i.e., contiguous lengths of homozygous genotypes observed in an individual's chromosome., Results: The objective of this study was to evaluate the association between ROH and sire conception rate. ROH were evaluated using 268 k genetic markers in 11,790 US Holstein bulls. Interestingly, either the sum, mean, or maximum length of ROH were negatively associated with bull fertility. The association analysis between ROH and sire fertility was performed comparing 300 high-fertility vs. 300 low-fertility bulls. Both the average and sum of ROH length were higher in the low-fertility group. The enrichment of ROH regions in bulls with low fertility was assessed using a Fisher's exact test. Nine regions were significantly enriched in low-fertility compared to high-fertility bulls. Notably, these regions harbor genes that are closely related to sperm biology and male fertility, including genes exclusively or highly expressed in testis., Conclusions: The results of this study can help not only to manage inbreeding in genomic selection programs by designing custom mating schemes, but also to better understand the mechanisms underlying male fertility in dairy cattle.

Uterine capacity (UC), defined as the total number of kits from unilaterally ovariectomized does at birth, has a high genetic correlation with litter size. The aim of our research was to identify genomic regions associated with litter size traits through a genomewide association study using rabbits from a divergent selection experiment for UC. A high-density SNP array (200K) was used to genotype 181 does from a control population, high and low UC lines. Traits included total number born (TNB), number born alive (NBA), number born dead, ovulation rate (OR), implanted embryos (IE) and embryo, foetal and prenatal survivals at second parity. We implemented the Bayes B method and the associations were tested by Bayes factors and the percentage of genomic variance (GV) explained by windows. Different genomic regions associated with TNB, NBA, IE and OR were found. These regions explained 7.36%, 1.27%, 15.87% and 3.95% of GV, respectively. Two consecutive windows on chromosome 17 were associated with TNB, NBA and IE. This genomic region accounted for 6.32% of GV of TNB. In this region, we found the BMP4, PTDGR, PTGER2, STYX and CDKN3 candidate genes which presented functional annotations linked to some reproductive processes. Our findings suggest that a genomic region on chromosome 17 has an important effect on litter size traits. However, further analyses are needed to validate this region in other maternal rabbit lines., (© 2019 Blackwell Verlag GmbH.)

Copy number variation (CNV) is an important source of genetic variability in human or animal genomes and play key roles in phenotypic diversity and disease susceptibility. In the present study, we performed a genome-wide analysis for CNV detection using SNP genotyping data of 857 Large White pigs. A total of 312 CNV regions (CNVRs) were detected with the PennCNV algorithm, which covered 57.76 Mb of the pig genome and correspond to 2.36% of the genome sequence. The length of the CNVRs on autosomes ranged from 1.77 Kb to 1.76 Mb with an average of 185.11 Kb. Of these, 220 completely or partially overlapped with 1,092 annotated genes, which enriched a wide variety of biological processes. Comparisons with previously reported pig CNVR revealed 92 (29.49%) novel CNVRs. Experimentally, 80% of CNVRs selected randomly were validated by quantitative PCR (qPCR). We also performed an association analysis between some of the CNVRs and reproductive traits, with results demonstrating the potential importance of CNVR61 and CNVR283 associated with litter sizes. Notably, the GPER1 gene located in CNVR61 plays a key role in reproduction. Our study is an important complement to the CNV map in the pig genome and provides valuable information for investigating the association between genomic variation and economic traits., (© 2019 Blackwell Verlag GmbH.)

Equine insect bite hypersensitivity (IBH) is a pruritic skin allergy caused primarily by biting midges, Culicoides spp. IBH susceptibility has polygenic inheritance and occurs at high frequencies in several horse breeds worldwide, causing increased costs and reduced welfare of affected horses. The aim of this study was to identify and validate single nucleotide polymorphisms (SNPs) associated with equine IBH susceptibility. After quality control, 33,523 SNPs were included in a Bayesian genome-wide association study on 177 affected and 178 unaffected Icelandic horses. We report associated regions in E. caballus (ECA) 1, 3, 15 and 18, overlapping with known IBH QTLs in horses, and novel regions containing several genes, together explaining 11.46% of the total genetic variance. For validation, three SNPs on ECA 1 and ECA X (explaining the largest percentage of genetic variance) within 1-mb genomic windows for IBH were genotyped in an independent population of 280 Exmoor ponies. The associated genomic region (152-153 mb) on ECA 1 was confirmed in Exmoor ponies and contains the AQR gene involved in splicing processes and a long non-coding RNA. This study confirms the polygenic nature of IBH susceptibility and suggests a role of transcriptional regulatory mechanisms (e.g., alternative splicing) for IBH predisposition in these horse breeds., (© 2019 Blackwell Verlag GmbH.)

Selection for bulls that would reach puberty early reduces the generation interval and increases fertility and herd productivity. Despite its economic importance, there are few QTL associated with age at puberty described in the literature. In this study, a weighted single-step genome-wide association study was performed to detect genomic regions and putative candidate genes related to age at puberty in young Nelore bulls. Several protein-coding genes related to spermatogenesis functions were identified within the genomic regions that explain more than 0.5% of the additive genetic variance for age at puberty in Nelore bulls, such as ADAM11, BRCA1, CSNK2A, CREBBP, MEIOC, NDRG2, NECTIN3, PARP2, PARP9, PRSS21, RAD51C, RNASE4, SLX4, SPA17, TEX14, TIMP2 and TRIP13 gene. Enrichment analysis by DAVID also revealed several GO terms related to spermatogenesis such as DNA replication (GO:0006260), male meiosis I (GO:0007141), double-strand break repair (GO:0006302), base excision repair (GO:0006284), apoptotic process (GO:0006915), cell-cell adhesion (GO: 0098609) and focal adhesion (GO:0005925). The heritability for age at puberty shows that this trait can be improved based on traditional EBV selection. Adding genomic information to the system helps to elucidate genes and molecular mechanisms controlling the sexual precocity and could help to predict sexual precocity in Nelore bulls with greater accuracy at younger age, which would speed up the breeding programme for this breed., (© 2019 Blackwell Verlag GmbH.)

This research communication describes a genome-wide association study for Italian buffalo mammary gland morphology. Three single nucleotide polymorphisms (AX-85117983, AX-8509475 and AX-85117518) were identified to be significantly associated with buffalo anterior teat length, posterior teat length and distance between anterior and posterior teat, respectively. Two significant signals for buffalo mammary gland morphology were observed in two genomic regions on the chromosome 10, and chromosome 20. One of the regions located on the chromosome 10 has the most likely candidate genes ACTC1 and GJD2, both of which have putative roles in the regulation of mammary gland development. This study provides new insights into the genetic variants of buffalo mammary gland morphology and may be beneficial for understanding of the genetic regulation of mammary growth.

Actinobacillus (A.) pleuropneumoniae is one of the most important respiratory pathogens in global pig production. Antimicrobial treatment and vaccination provide only limited protection, but genetic disease resistance is a very promising alternative for sustainable prophylaxis. Previous studies have discovered multiple QTL that may explain up to 30% of phenotypic variance. Based on these findings, the aim of the present study was to use genomic sequencing to identify genetic markers for resistance to pleuropneumonia in a segregating commercial German Landrace line. 163 pigs were infected with A. pleuropneumoniae Serotype 7 through a standardized aerosol infection method. Phenotypes were accurately defined on a clinical, pathological and microbiological basis. The 58 pigs with the most extreme phenotypes were genotyped by sequencing (next-generation sequencing). SNPs were used in a genome-wide association study. The study identified genome-wide associated SNPs on three chromosomes, two of which were chromosomes of QTL which had been mapped in a recent experiment. Each variant explained up to 20% of the total phenotypic variance. Combined, the three variants explained 52.8% of the variance. The SNPs are located in genes involved in the pathomechanism of pleuropneumonia. This study confirms the genetic background for the host's resistance to pleuropneumonia and indicates a potential role of three candidates on SSC2, SSC12 and SSC15. Favorable gene variants are segregating in commercial populations. Further work is needed to verify the results in a controlled study and to identify the functional QTN.

Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 ( GPIHBP1 ) is among the many candidate genes for regulating milk production traits in dairy cattle that have been identified via quantitative trait locus (QTL) mapping and genome-wide association studies (GWAS). Our previous studies confirmed that a G-to-A mutation at chr14:2553998 is the main cause of GPIHBP1 -related effects on milk fat content. In this study, we discovered that GPIHBP1 may be a strong candidate gene for the regulation of milk protein traits. We performed overexpression and RNAi experiments to assess GPIHBP1 in bovine primary mammary epithelial cells (BMECs) and identified mRNA expression patterns of several important milk protein-related genes using real-time quantitative PCR. After the transient transfection of BMECs with GPIHBP1 , the transcription levels of casein genes ( CSN1S1 , CSN1S2 , CSN2, and CSN3 ) and lactoferrin ( LTF ) decreased, whereas beta-lactoglobulin ( LGB ) expression increased. The GPIHBP1 RNAi experiment produced changes in gene expression that were completely opposite to those observed in the GPIHBP1 overexpression experiment. Furthermore, among the assessed genes, CSN3, LTF, and LGB exhibited significant changes in mRNA expression ( p  < 0.05). The findings of this study show that bovine GPIHBP1 is involved in the process of milk protein biosynthesis and may be considered as a functional gene for the milk protein yield trait.

Background: Genome-wide association studies (GWAS) are extensively used to identify single nucleotide polymorphisms (SNP) underlying the genetic variation of complex traits. However, much uncertainly often still exists about the causal variants and genes at quantitative trait loci (QTL). The aim of this study was to identify QTL associated with residual feed intake (RFI) and genes in these regions whose expression is also associated with this trait. Angus cattle (2190 steers) with RFI records were genotyped and imputed to high density arrays (770 K) and used for a GWAS approach to identify QTL associated with RFI. RNA sequences from 126 Angus divergently selected for RFI were analyzed to identify the genes whose expression was significantly associated this trait with special attention to those genes residing in the QTL regions., Results: The heritability for RFI estimated for this Angus population was 0.3. In a GWAS, we identified 78 SNPs associated with RFI on six QTL (on BTA1, BTA6, BTA14, BTA17, BTA20 and BTA26). The most significant SNP was found on chromosome BTA20 (rs42662073) and explained 4% of the genetic variance. The minor allele frequencies of significant SNPs ranged from 0.05 to 0.49. All regions, except on BTA17, showed a significant dominance effect. In 1 Mb windows surrounding the six significant QTL, we found 149 genes from which OAS2, STC2, SHOX, XKR4, and SGMS1 were the closest to the most significant QTL on BTA17, BTA20, BTA1, BTA14, and BTA26, respectively. In a 2 Mb windows around the six significant QTL, we identified 15 genes whose expression was significantly associated with RFI: BTA20) NEURL1B and CPEB4; BTA17) RITA1, CCDC42B, OAS2, RPL6, and ERP29; BTA26) A1CF, SGMS1, PAPSS2, and PTEN; BTA1) MFSD1 and RARRES1; BTA14) ATP6V1H and MRPL15., Conclusions: Our results showed six QTL regions associated with RFI in a beef Angus population where five of these QTL contained genes that have expression associated with this trait. Therefore, here we show that integrating information from gene expression and GWAS studies can help to better understand the genetic mechanisms that determine variation in complex traits.

High-density genetic map and quantitative trait loci (QTL) mapping are powerful tools for identifying genomic regions that may be responsible for such polygenic trait as growth. A high-density genetic linkage map was constructed by sequencing 198 individuals in a F 1 family of silver carp (Hypophthalmichthys molitrix) in this study. This genetic map spans a length of 2,721.07 cM with 3,134 SNPs distributed on 24 linkage groups (LGs). Comparative genomic mapping presented a high level of syntenic relationship between silver carp and zebrafish. We detected one major and nineteen suggestive QTL for 4 growth-related traits (body length, body height, head length and body weight) at 6, 12 and 18 months post hatch (mph), explaining 10.2~19.5% of phenotypic variation. All six QTL for growth traits of 12 mph generally overlapped with QTL for 6 mph, while the majority of QTL for 18 mph were identified on two additional LGs, which may reveal a different genetic modulation during early and late muscle growth stages. Four potential candidate genes were identified from the QTL regions by homology searching of marker sequences against zebrafish genome. Hepcidin, a potential candidate gene identified from a QTL interval on LG16, was significantly associated with growth traits in the analyses of both phenotype-SNP association and mRNA expression between small-size and large-size groups of silver carp. These results provide a basis for elucidating the genetic mechanisms for growth and body formation in silver carp, a world aquaculture fish.

Background: Climate change is expected to have a negative impact on food availability. While most efforts have been directed to reducing greenhouse gas emissions, complementary strategies are necessary to control the detrimental effects of climate change on farm animal performance. The objective of this study was to develop novel animal resilience phenotypes using reaction norm slopes, and examine their genetic and genomic parameters. A closely monitored dairy goat population was used for this purpose., Results: Individual animals differed in their response to changing atmospheric temperature and a temperature-humidity index. Significant genetic variance and heritability estimates were derived for these animal resilience phenotypes. Furthermore, some resilience traits had a significant unfavourable genetic correlation with animal performance. Genome-wide association analyses identified several candidate genes related to animal resilience to environment change., Conclusions: Heritable variation exists among dairy goats in their production response to fluctuating weather variables. Results may inform future breeding programmes aimed to ensure efficient animal performance under changing climatic conditions.

Background: Salmonella infection is a serious concern in poultry farming because of its impact on both economic loss and human health. Chicks aged 20 days or less are extremely vulnerable to Salmonella pullorum (SP), which causes high mortality. Furthermore, an outbreak of SP infection can result in a considerable number of carriers that become potential transmitters, thus, threatening fellow chickens and offspring. In this study, we conducted a genome-wide association study (GWAS) to detect potential genomic loci and candidate genes associated with two disease-related traits: death and carrier state., Methods: In total, 818 birds were phenotyped for death and carrier state traits through a SP challenge experiment, and genotyped by using a 600 K high-density single nucleotide polymorphism (SNP) array. A GWAS using a single-marker linear mixed model was performed with the GEMMA software. RNA-sequencing on spleen samples was carried out for further identification of candidate genes., Results: We detected a region that was located between 33.48 and 34.03 Mb on chicken chromosome 4 and was significantly associated with death, with the most significant SNP (rs314483802) accounting for 11.73% of the phenotypic variation. Two candidate genes, FBXW7 and LRBA, were identified as the most promising genes involved in resistance to SP. The expression levels of FBXW7 and LRBA were significantly downregulated after SP infection, which suggests that they may have a role in controlling SP infections. Two other significant loci and related genes (TRAF3 and gga-mir-489) were associated with carrier state, which indicates a different polygenic determinism compared with that of death. In addition, genomic inbreeding coefficients showed no correlation with resistance to SP within each breed in our study., Conclusions: The results of this GWAS with a carefully organized Salmonella challenge experiment represent an important milestone in understanding the genetics of infectious disease resistance, offer a theoretical basis for breeding SP-resistant chicken lines using marker-assisted selection, and provide new information for salmonellosis research in humans and other animals.

Background: This study aimed at identifying genomic regions that underlie genetic variation of worm egg count, as an indicator trait for parasite resistance in a large population of Australian sheep, which was genotyped with the high-density 600 K Ovine single nucleotide polymorphism array. This study included 7539 sheep from different locations across Australia that underwent a field challenge with mixed gastrointestinal parasite species. Faecal samples were collected and worm egg counts for three strongyle species, i.e. Teladorsagia circumcincta, Haemonchus contortus and Trichostrongylus colubriformis were determined. Data were analysed using genome-wide association studies (GWAS) and regional heritability mapping (RHM)., Results: Both RHM and GWAS detected a region on Ovis aries (OAR) chromosome 2 that was highly significantly associated with parasite resistance at a genome-wise false discovery rate of 5%. RHM revealed additional significant regions on OAR6, 18, and 24. Pathway analysis revealed 13 genes within these significant regions (SH3RF1, HERC2, MAP3K, CYFIP1, PTPN1, BIN1, HERC3, HERC5, HERC6, IBSP, SPP1, ISG20, and DET1), which have various roles in innate and acquired immune response mechanisms, as well as cytokine signalling. Other genes involved in haemostasis regulation and mucosal defence were also detected, which are important for protection of sheep against invading parasites., Conclusions: This study identified significant genomic regions on OAR2, 6, 18, and 24 that are associated with parasite resistance in sheep. RHM was more powerful in detecting regions that affect parasite resistance than GWAS. Our results support the hypothesis that parasite resistance is a complex trait and is determined by a large number of genes with small effects, rather than by a few major genes with large effects.

The aim of this study was to investigate microRNA (miRNA) differential expression in the two most common equine skin tumours, equine sarcoid (ES) and squamous cell carcinoma (SCC), and its potential influence on the tumour microenvironment at post-transcriptional level. We investigated miRNA fingerprints in four subgroups: mild (ESM) and aggressive (ESA) ES and ocular SCC (oSCC) and genital SCC (gSCC). Three tumours and three control samples were included in each of the four subgroups. Following next generation sequencing, miRNA differential expression analysis using DESeq2 was carried out. Pathways associated with the human mature homologues of identified dysregulated miRNAs were predicted using DIANA- miRPath v3.0. When comparing tumour vs control tissue, 57 miRNAs in ESM, six in ESA, 47 in oSCC and zero in gSCC were found to be differentially expressed and may thus serve as potential diagnostic tissue biomarkers. Whereas, ES lesions in general were associated with downregulation of the miR-200 family, which may trigger epithelial-mesenchymal transition, ESM lesions were associated with upregulation of the proposed tumour-suppressive miRNA cluster on equine chromosome 24. In contrast, the oSCC tumours showed downregulation of this cluster as well as downregulation of the miR-34 family, which may favour oSCC tumour cell metabolism. To further validate the proposed diagnostic miRNA fingerprints and their suggested biological effects, further miRNA studies need to be carried out in larger study cohorts., (© 2019 John Wiley & Sons Ltd.)

Haematological and clinical-biochemical parameters are considered indicators of the physiological/health status of animals and might serve as intermediate phenotypes to link physiological aspects to production and disease resistance traits. The dissection of the genetic variability affecting these phenotypes might be useful to describe the resilience of the animals and to support the usefulness of the pig as animal model. Here, we analysed 15 haematological and 15 clinical-biochemical traits in 843 Italian Large White pigs, via three genome-wide association scan approaches (single-trait, multi-trait and Bayesian). We identified 52 quantitative trait loci (QTLs) associated with 29 out of 30 analysed blood parameters, with the most significant QTL identified on porcine chromosome 14 for basophil count. Some QTL regions harbour genes that may be the obvious candidates: QTLs for cholesterol parameters identified genes (ADCY8, APOB, ATG5, CDKAL1, PCSK5, PRL and SOX6) that are directly involved in cholesterol metabolism; other QTLs highlighted genes encoding the enzymes being measured [ALT (known also as GPT) and AST (known also as GOT)]. Moreover, the multivariate approach strengthened the association results for several candidate genes. The obtained results can contribute to define new measurable phenotypes that could be applied in breeding programs as proxies for more complex traits.

I abandoned my original career choice of high school teaching to pursue dentistry and soon abandoned that path for genetics. The latter decision was due to a challenge by a professor that led to me reading Nobel speeches by pioneer geneticists before I had formal exposure to the subject. Even then, I was 15 years into my career before my interest in rodent genomes gave way to mapping cattle genes. Events behind these twists and turns in my career path comprise the first part of this review. The remainder is a review of the development of the field of bovine genomics from my personal perspective. I have had the pleasure of working with outstanding graduate students, postdocs, and colleagues to contribute my small part to a discipline that has evolved from a few individuals mapping an orphan genome to a discipline underlying a revolution in animal breeding.

Human milk contains abundant oligosaccharides (OS) which are believed to have strong health benefits for neonates. OS are a minor component of bovine milk and little is known about how the production of OS is regulated in the bovine mammary gland. We have measured the abundance of 12 major OS in milk of 360 cows, which had high density SNP marker genotypes. Most of the OS were found to be highly heritable (h 2 between 50 and 84%). A genome-wide association study allowed us to fine-map several QTL and identify candidate genes with major effects on five OS. Among them, a putative causal mutation close to the ABO gene on Chromosome 11 accounted for approximately 80% of genetic variance for two OS, N-acetylgalactosaminyllactose and lacto-N-neotetraose. This mutation lies very close to a variant associated with the expression levels of ABO. A third QTL mapped close to ST3GAL6 on Chromosome 1 explaining 33% of genetic variation of an abundant OS, 3'-sialyllactose. The presence of major gene effects suggests that targeted marker-assisted selection would lead to a significant increase in the level of these OS in milk. This is the first attempt to map candidate genes and causal mutations for bovine milk OS.

Selection for rapid growth in chickens has always been accompanied by increased fat deposition and excessive fat deposition, especially abdominal fat, cannot only decrease feed efficiency but also cause many diseases. Finding the candidate genes associated with abdominal fat deposition is essential for breeding. To identify these candidate genes, we applied linkage disequilibrium and selection signature analysis using chicken 60 k single nucleotide polymorphism (SNP) chips in two broiler lines divergently selected for abdominal fat content for 11 generations. After quality control, 46,033 SNPs were left for analysis. Using these SNPs, we found that r2 was 0.06 to 0.14 in the lean line and 0.07 to 0.13 in the fat line for all 28 chromosomes (except GGA16). Pairwise SNP distances <25 kb showed a mean r2 = 0.33 in the lean line and r2 = 0.32 in the fat line. The fixation index (FST) analysis was carried out and 46 SNPs with the top 0.1% of the FST value was detected as the loci with selection signatures. Besides FST, hapFLK was also used to detect selection signatures for abdominal fat content. A total of 11 genes, including transient receptor potential cation channel subfamily C member 4, estrogen related receptor gamma, fibroblast growth factor 13, G-protein-signaling modulator 2, RAR related orphan receptor A, phospholipase A2 group X, mitochondrial ribosomal protein L28, metadherin, calcitonin receptor like receptor, serine/threonine kinase 39, and nuclear factor I A, were detected as the important candidate genes for abdominal fat deposition based on their basic functions. The results of the present study may benefit the understanding of genetic mechanism of abdominal fat deposition in chicken., (© 2018 Poultry Science Association Inc.)

In cattle breeding, the development of genomic selection strategies based on single nucleotide polymorphism (SNP) interrogation has led to improved rates of genetic gain. Additionally, the application of genomic selection to in-vitro produced (IVP) embryos is expected to bring further benefits thanks to the ability to test a greater number of individuals before establishing a pregnancy and to ensure only carriers of desirable traits are born. However, aneuploidy, a leading cause of developmental arrest, is known to be common in IVP embryos. Karyomapping is a comprehensive screening test based on SNP typing that can be used for simultaneous genomic selection and aneuploidy detection, offering the potential to maximize pregnancy rates. Moreover, Karyomapping can be used to characterize the frequency and parental origin of aneuploidy in bovine IVP embryos, which have remained underexplored to date. Here, we report the use of Karyomapping to characterize the frequency and parental origin of aneuploidy in IVP bovine embryos in order to establish an estimate of total aneuploidy rates in each parental germline. We report an estimate of genome wide recombination rate in cattle and demonstrate, for the first time, a proof of principle for the application of Karyomapping to cattle breeding, with the birth of five calves after screening. This combined genomic selection and aneuploidy screening approach was highly reliable, with calves showing 98% concordance with their respective embryo biopsies for SNP typing and 100% concordance with their respective biopsies for aneuploidy screening. This approach has the potential to simultaneously improve pregnancy rates following embryo transfer and the rate of genetic gain in cattle breeding, and is applicable to basic research to investigate meiosis and aneuploidy., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The first and only published version of the rat reference genome sequence was RGSC3.1, accomplished by the Rat Genome Sequencing Project Consortium. Here we present the history of the community effort in the correction of sequence errors and filling missing gaps in the process of refining and providing researchers with a high-quality rat reference sequence. The genome assembly improvements, addition of different evidence resources over time, such as RNA-Seq data, and software development methodologies had a positive impact on the gene model annotations. Over the years we observed a great increase in the numbers of genes, protein coding sequences, predicted transcripts and transcript features. Before the sequencing of the rat genome was possible, first biochemical and next genomic markers like RAPD, AFLP, RFLP, and SSLP were fundamental in research studies involving cross-breeding between different rat strains, in finding the level of polymorphism, linkage mapping, and phylogeny. Linkage maps provide information on recombination rates, give insight into intra- and interspecies gene rearrangements, and help to identify Mendelian loci and Quantitative Trait Loci (QTL). In the 1990s many reports were published on the construction of rat linkage maps that incorporated increasing numbers of markers and facilitated the localization of disease loci. Current genetic monitoring and linkage mapping relies on single nucleotide polymorphisms (SNPs). The Rat Genome Database collects information on genetic variation from the worldwide community of rat researchers and provides tools for searching and retrieving these data. As of today we show details about almost 605 million variants coming from many studies in our Variant Visualizer tool.

For nearly a century, the rat has served as a key model for studying the pathophysiology and genetic risk modifiers of breast cancer. Rat mammary tumors that initiate after exposure to carcinogens or estrogens closely resemble the etiological, histopathological, and genomic features of human breast cancer. Recent developments in genome-editing techniques in the rat have also enabled the development of sophisticated models for identifying the genetic modifiers of the nonmalignant tumor microenvironment that contribute to the formation, progression, and outcome of breast cancer. In this protocol review, we discuss the current methodologies for the three genetic mapping techniques in the rat that are widely used for identifying and testing the heritable genetic modifiers of breast cancer.

Our knowledge of Testudines evolution is limited by the lack of modern cytogenetic data. Compared to other reptiles, there is little information even on chromosome banding, let alone molecular cytogenetic data. Here, we provide detailed information on the karyotype of the European pond turtle Emys orbicularis, a model Emydidae, employing both chromosome banding and molecular cytogenetics. We provide a high-resolution G-banded karyotype and a map of rDNA genes and telomeric sequences using fluorescence in situ hybridization. We test hypotheses of sex-determining mechanisms in Emys by comparative genomic hybridization to determine if Emys has a cryptic sex-specific region. Our results provide valuable data to guide future efforts on genome sequencing and anchoring in Emydidae and for understanding karyotype evolution in Testudines., (© 2019 S. Karger AG, Basel.)

In this chapter we will review both the rationale and experimental design for using Heterogeneous Stock (HS) populations for fine-mapping of complex traits in mice and rats. We define an HS as an outbred population derived from an intercross between two or more inbred strains. HS have been used to perform genome-wide association studies (GWAS) for multiple behavioral, physiological, and gene expression traits. GWAS using HS require four key steps, which we review: selection of an appropriate HS population, phenotyping, genotyping, and statistical analysis. We provide advice on the selection of an HS, comment on key issues related to phenotyping, discuss genotyping methods relevant to these populations, and describe statistical genetic analyses that are applicable to genetic analyses that use HS.

The karyotypes of the family Parodontidae consist of 2n = 54 chromosomes. The main chromosomal evolutionary changes of its species are attributed to chromosome rearrangements in repetitive DNA regions in their genomes. Physical mapping of the H1 and H4 histones was performed in 7 Parodontidae species to analyze the chromosome rearrangements involved in karyotype diversification in the group. In parallel, the observation of a partial sequence of an endogenous retrovirus (ERV) retrotransposon in the H1 histone sequence was evaluated to verify molecular co-option of the transposable elements (TEs) and to assess paralogous sequence dispersion in the karyotypes. Six of the studied species had an interstitial histone gene cluster in the short arm of the autosomal pair 13. Besides this interstitial cluster, in Apareiodon davisi, a probable further site was detected in the terminal region of the long arm in the same chromosome pair. The H1/H4 clusters in Parodon cf. pongoensis were located in the smallest chromosomes (pair 20). In addition, scattered H1 signals were observed on the chromosomes in all species. The H1 sequence showed an ERV in the open reading frame (ORF), and the scattered H1 signals on the chromosomes were attributed to the ERV's location. The H4 sequence had no similarity to the TEs and displayed no dispersed signals. Furthermore, the degeneration of the inner ERV in the H1 sequence (which overlapped a stretch of the H1 ORF) was discussed regarding the likelihood of molecular co-option of this retroelement in histone gene function in Parodontidae., (© 2019 S. Karger AG, Basel.)

A high-density genetic linkage map is essential for the studies of comparative genomics and gene mapping, and can facilitate assembly of reference genome. Herein, we constructed a high-density genetic linkage map with 8,094 SNPs selected from 113 sequenced fish of a F1 family. Ultimately, the consensus map spanned 3818.24 cM and covered nearly the whole genome (99.4%) with a resolution of 0.47 cM. 1,457 scaffolds spanning 435.15 Mb were anchored onto 24 linkage groups, accounting for 80.7% of the draft genome assembly of the yellow drum. Comparative genomic analyses with medaka and zebrafish genomes showed superb chromosome-scale synteny between yellow drum and medaka. QTL mapping and association analysis congruously revealed 22 QTLs for growth-related traits and 13 QTLs for sex dimorphism. Some important candidate genes such as PLA2G4A, BRINP3 and P2RY1 were identified from these growth-related QTL regions. A gene family including DMRT1, DMRT2 and DMRT3 was identified from these sex-related QTL regions on the linkage group LG9. We demonstrate that this linkage map can facilitate the ongoing marker-assisted selection and genomic and genetic studies for yellow drum.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development.

To obtain a better understanding of the mitochondrial genome in Perlodidae and the phylogeny of Perloidea, we sequenced two perlodid mitochondrial genomes and present comparative analyses in the family Perlodidae. Our results show that genome organization, base composition, codon usage and non-coding and overlapping regions, the sequences of mitochondrial transcription termination factor (DmTTF) and structural elements in control region were conserved in Perlodidae. The unique non-coding regions in COI-trnL2 and trnL2-COII were present in Perlodidae but were incomplete or absent from other stoneflies, and we also discuss the conservative property of the sequences between trnE and trnF, trnS1 and ND1. The secondary structure of tRNAs showed that the trnK, trnP, trnS1 and trnW were identical and the trnS1 could not be folded into typical secondary structure due to its absence of DHU arm. Phylogenetic implications supported that Chloroperlidae is a sister group to Perlodidae and the Perlidae is a sister group to the clade Chloroperlidae + Perlodidae. This study contributes to understanding the comparative mitogenomic analysis of Perlodidae and phylogenetic relationships within the Perloidea., (Copyright © 2018 Elsevier B.V. All rights reserved.)