Characterization of runs of homozygosity, heterozygosity-enriched regions, and population structure in cattle populations selected for different breeding goals.

BACKGROUND: A decline in the level of genetic diversity in livestock can result in reduced response to selection, greater incidence of genetic defects, and inbreeding depression. In this context, various metrics have been proposed to assess the level of genetic diversity in selected populations. Therefore, the main goals of this study were to: 1) investigate the population structure of 16 cattle populations from 15 different pure breeds or composite populations, which have been selected for different breeds goals; and, 2) identify and compare runs of homozygosity (ROH) and heterozygosity-enriched regions (HER) based on different single nucleotide polymorphism (SNP) panels and whole-genome sequence data (WGS), followed by functional genomic analyses. RESULTS: A total of 24,187 ROH were found across all cattle populations, with 55% classified in the 2-4 Mb size group. Fourteen homozygosity islands were found in five populations, where four ROH islands located on BTA1, BTA5, BTA16, and BTA19 overlapped between the Brahman (BRM) and Gyr (GIR) breeds. A functional analysis of the genes found in these islands revealed candidate genes known to play a role in the melanogenesis, prolactin signaling, and calcium signaling pathways. The correlations between inbreeding metrics ranged from 0.02 to 0.95, where the methods based on homozygous genotypes (FHOM), uniting of gametes (FUNI), and genotype additive variance (FGRM) showed strong correlations among them. All methods yielded low to moderate correlations with the inbreeding coefficients based on runs of homozygosity (FROH). For the HER, 3576 runs and 26 islands, distributed across all autosomal chromosomes, were found in regions containing genes mainly related to the immune system, indicating potential balancing selection. Although the analyses with WGS did not enable detection of the same island patterns, it unraveled novel regions not captured when using SNP panel data. CONCLUSIONS: The cattle populations that showed the largest amount of ROH and HER were Senepol (SEN) and Montana (MON), respectively. Overlapping ROH islands were identified between GIR and BRM breeds, indicating a possible historical connection between the populations. The distribution and pattern of ROH and HER are population specific, indicating that different breeds have experienced divergent selection processes or different genetic processes.

A Systematic Review of Genomic Regions and Candidate Genes Underlying Behavioral Traits in Farmed Mammals and Their Link with Human Disorders.

The main objectives of this study were to perform a systematic review of genomic regions associated with various behavioral traits in the main farmed mammals and identify key candidate genes and potential causal mutations by contrasting the frequency of polymorphisms in cattle breeds with divergent behavioral traits (based on a subjective clustering approach). A total of 687 (cattle), 1391 (pigs), and 148 (sheep) genomic regions associated with 37 (cattle), 55 (pigs), and 22 (sheep) behavioral traits were identified in the literature. In total, 383, 317, and 15 genes overlap with genomic regions identified for cattle, pigs, and sheep, respectively. Six common genes (e.g., NR3C2, PITPNM3, RERG, SPNS3, U6, and ZFAT) were found for cattle and pigs. A combined gene-set of 634 human genes was produced through identified homologous genes. A total of 313 out of 634 genes have previously been associated with behavioral, mental, and neurologic disorders (e.g., anxiety and schizophrenia) in humans. Additionally, a total of 491 candidate genes had at least one statistically significant polymorphism (p-value < 0.05). Out of those, 110 genes were defined as having polymorphic regions differing in greater than 50% of exon regions. Therefore, conserved genomic regions controlling behavior were found across farmed mammal species and humans.

Genetic Parameters and Genome-Wide Association Studies for Anti-Müllerian Hormone Levels and Antral Follicle Populations Measured After Estrus Synchronization in Nellore Cattle.

Reproductive efficiency plays a major role in the long-term sustainability of livestock industries and can be improved through genetic and genomic selection. This study aimed to estimate genetic parameters (heritability and genetic correlation) and identify genomic regions and candidate genes associated with anti-Müllerian hormone levels (AMH) and antral follicle populations measured after estrous synchronization (AFP) in Nellore cattle. The datasets included phenotypic records for 1099 and 289 Nellore females for AFP and AMH, respectively, high-density single nucleotide polymorphism (SNP) genotypes for 944 animals, and 4129 individuals in the pedigree. The heritability estimates for AMH and AFP were 0.28 ± 0.07 and 0.30 ± 0.09, and the traits were highly and positively genetically correlated (rG = 0.81 ± 0.02). These findings indicated that these traits can be improved through selective breeding, and substantial indirect genetic gains are expected by selecting for only one of the two traits. A total of 31 genomic regions were shown to be associated with AMH or AFP, and two genomic regions located on BTA1 (64.9-65.0 Mb and 109.1-109.2 Mb) overlapped between the traits. Various candidate genes were identified to be potentially linked to important biological processes such as ovulation, tissue remodeling, and the immune system. Our findings support the use of AMH and AFP as indicator traits to genetically improve fertility rates in Nellore cattle and identify better oocyte donors.

Genetic Architecture of Carcass and Meat Quality Traits in Montana Tropical® Composite Beef Cattle.

The Montana Tropical® Composite is a recently developed beef cattle population that is rapidly expanding in Brazil and other tropical countries. This is mainly due to its improved meat quality and adaptation to tropical climate conditions compared to Zebu and Taurine cattle breeds, respectively. This study aimed to investigate the genetic architecture of ultrasound-based carcass and meat quality traits in Montana Tropical® Composite beef cattle. Therefore, we estimated variance components and genetic parameters and performed genome-wide association studies using the weighted single-step Genomic Best Linear Unbiased Prediction (GBLUP) approach. A pedigree dataset containing 28,480 animals was used, in which 1,436 were genotyped using a moderate-density Single Nucleotide Polymorphism panel (30K; 30,105 SNPs). A total of 9,358, 5,768, 7,996, and 1,972 phenotypic records for the traits Longissimus muscle area (LMA), backfat thickness (BFT), rump fat thickness (RFT), and for marbling score (MARB), respectively, were used for the analyses. Moderate to high heritability estimates were obtained and ranged from 0.16 ± 0.03 (RFT) to 0.33 ± 0.05 (MARB). A high genetic correlation was observed between BFT and RFT (0.97 ± 0.02), suggesting that a similar set of genes affects both traits. The most relevant genomic regions associated with LMA, BFT, RFT, and MARB were found on BTA10 (5.4-5.8 Mb), BTA27 (25.2-25.5 Mb), BTA18 (60.6-61.0 Mb), and BTA21 (14.8-15.4 Mb). Two overlapping genomic regions were identified for RFT and MARB (BTA13:47.9-48.1 Mb) and for BFT and RFT (BTA13:61.5-62.3 Mb). Candidate genes identified in this study, including PLAG1, LYN, WWOX, and PLAGL2, were previously reported to be associated with growth, stature, skeletal muscle growth, fat thickness, and fatty acid composition. Our results indicate that ultrasound-based carcass and meat quality traits in the Montana Tropical® Composite beef cattle are heritable, and therefore, can be improved through selective breeding. In addition, various novel and already known genomic regions related to these traits were identified, which contribute to a better understanding of the underlying genetic background of LMA, BFT, RFT, and MARB in the Montana Tropical Composite population.

Genome-wide scan for runs of homozygosity in the composite Montana Tropical® beef cattle.

The aim of this study was to assess the distribution of runs of homozygosity (ROH) and autozygosity islands in the composite Montana Tropical® beef cattle to explore hotspot regions which could better characterize the different biological types within the composite breed. Montana animals (n = 1,436) were genotyped with the GGP-LD BeadChip (~30,000 markers). ROH was identified in every individual using the plink v1.90 software. Medium and long ROH prevailed in the genome, which accounted for approximately 74% of all ROH detected. On an average, 2.0% of the genome was within ROH, agreeing with the pedigree-based inbreeding coefficient. The Montana cattle with a higher proportion of productive breed types showed the highest number of autozygosity islands (n = 17), followed by those with a higher proportion of breeds adapted to tropical environments (n = 15). Enriched terms (p < .05) associated with the immune and inflammatory response, homeostasis, reproduction, mineral absorption, and lipid metabolism were described within the autozygosity islands. In this regard, over-represented GO terms and KEGG pathways described in this population may play a key role in providing information to explore the genetic and biological mechanisms together with the genomic regions underlying each biological type that favoured their optimal performance ability in tropical and subtropical regions.

Intra-articular concentration of gentamicin administered by intravenous regional limb perfusion in healthy horses / Concentração intra-articular de gentamicina administrada por perfusão regional intravenosa em membros de equinos sadios

ABSTRACT: Intravenous regional limb perfusion (IRLP) is an efficient method to treat horses with synovial infections. However, information on the dose, volume, and intervals of administration is lacking. The aim of this study was to evaluate the intra-articular concentration of gentamicin administered by IRLP in horses over 24 h post-administration and evaluate the influence of the total perfused volume. Twenty horses were assigned to two treatment groups. Gentamicin 60 group (G60, n=10) and Gentamicin 250 group (G250, n=10) received IRLP of 6.6 mg/kg of gentamicin diluted in Ringer's lactate for a total volume of 60 ml (G60) and 250 ml (G250), respectively. Synovial fluid harvests were performed in the metacarpophalangeal joint before (0) and 4, 8, 12, 16, 20, and 24 hours after IRLP. Agar diffusion was the assay for measuring gentamicin concentrations. Four hours after IRLP, the intra-articular concentration of gentamicin was 47.58±49.21 μg/ml in G60 and 10.92±6.11 μg/ml in G250. During the 24 h of harvest, the intra-articular concentration of gentamicin remained above the minimum inhibitory concentration for horses (MIC; 2 μg/ml) in both experimental groups. In G60, the concentration of gentamicin in synovial fluid reached the maximal concentration and remained 8 to 10-fold higher than the MIC (Cmax: 16 to 20 μg/ml) during 12 h after IRLP. These findings support that IRLP with 6.6 mg/kg of gentamicin diluted to a volume of 60 ml promotes intra-articular concentrations higher than 250 ml, remaining above the MIC for 24 h and at the maximum concentration for 12 h.

RESUMO: A perfusão regional intravenosa (PRI) em membros de equinos é um método comprovadamente eficiente para o tratamento de infecções sinoviais, porém ainda existem lacunas quanto à dose, volume e intervalos de administração a serem utilizados. Neste estudo, objetivou-se avaliar a concentração intra-articular da gentamicina administrada por PRI em equinos, ao longo de 24 horas pós-administração, bem como avaliar a influência do volume total perfundido. Vinte equinos foram distribuídos em dois grupos experimentais, Grupo Gentamicina 60 (G60) e Grupo Gentamicina 250 (G250), representados por 10 equinos em cada grupo que receberam, por PRI, 6,6 mg/kg de gentamicina diluída em Ringer lactato para um total de 60 ml (G60) ou 250 ml (G250). As colheitas de líquido sinovial foram realizadas, na articulação metacarpo-falangeana, antes do início do experimento e após 4, 8, 12, 16, 20, e 24 horas. Difusão em ágar foi o método para doseamento das concentrações de gentamicina. Quatro horas após a PRI, a concentração intra-articular da gentamicina era de 47,58±49,21 µg/ml no G60 e 10,92±6,11 µg/ml no G250. Durante as 24 horas de colheita, a concentração intra-articular de gentamicina permaneceu acima da concentração inibitória mínima (CIM) (2 μg/ml) em ambos os grupos experimentais. No G60, as concentrações de gentamicina no líquido sinovial atingiram a concentração máxima e mantiveram-se 8 a 10 vezes mais elevadas que a CIM (Cmáx: 16 a 20 μg/ml) durante 12 horas após a PRI. Conclui-se que a PRI em membros, com 6,6 mg/kg de gentamicina diluída para o volume de 60 ml, promove concentrações intra-articulares mais elevadas que o volume de 250 ml, permanecendo acima da CIM durante 24 horas e em concentração máxima durante 12 horas.

Genomic regions and enrichment analyses associated with carcass composition indicator traits in Nellore cattle.

The aim of this study was to estimate genetic parameters and identify genomic regions associated with carcass traits obtained by ultrasound and visual scores in Nellore cattle. Data from ~66,000 animals from the National Association of Breeders and Researchers (ANCP) were used. The variance components for backfat thickness, rump fat thickness and Longissimus muscle area (LMA) were estimated considering a linear model whereas a threshold model for body structure (BS), finishing precocity (FP) and musculature (MS) traits. The SNP solutions were estimated using the ssGBLUP approach by considering windows of 10 consecutive SNPs. Regions that accounted for more than 1.0% of the additive genetic variance were used. Genes identified within the significant windows, such as FOXA3, AP2S1, FKRP, NPASI and ATP6V1G1, were found to be related with MS, while OMA1 and FFGY with BS and FP traits. The PLTP, TNNC2 and GPAT2 genes were found in the regions associated with LMA, as well as TKT, FNDC5 and CHRND can strongly be related with fat deposition. Gene enrichment analysis revealed processes that might be directly influenced the organism growth and development. These results should help to better understand the genetic and physiological mechanisms regulating growth and body composition, muscle tissue development and subcutaneous fat expression, and this information might be useful for future genomic studies in Nellore cattle.