Genome-wide landscape of runs of homozygosity and differentiation across Egyptian goat breeds.

Understanding the genomic features of livestock is essential for successful breeding programs and conservation. This information is scarce for local goat breeds in Egypt. In the current study, genomic regions with selection signatures were identified as well as runs of homozygosity (ROH), genomic inbreeding coefficients (FROH) and fixation index (FST) were detected in Egyptian Nubian, Damascus, Barki and Boer goat breeds. A total of 46,268 SNP markers and 337 animals were available for the genomic analyses. On average, 145.44, 42.02, 87.90 and 126.95 ROHs were detected per individual in the autosomal genome of the respective breeds. The mean accumulative ROH lengths ranged from 46.5 Mb in Damascus to 360 Mb in Egyptian Nubian. The short ROH segments (< 2 Mb) were most frequent in all breeds, while the longest ROH segments (> 16 Mb) were exclusively found in the Egyptian Nubian. The highest average FROH was observed in Egyptian Nubian (~ 0.12) followed by Boer (~ 0.11), while the lowest FROH was found in Damascus (~ 0.05) and Barki breed (~ 0.03). The estimated mean FST was 0.14 (Egyptian Nubian and Boer), 0.077 (Egyptian Nubian and Barki), 0.075 (Egyptian Nubian and Damascus), 0.071 (Barki and Boer), 0.064 (Damascus and Boer), and 0.015 (Damascus and Barki), for each pair of breeds. Interestingly, multiple SNPs that accounted for high FST values were observed on chromosome 6 in regions harboring ALPK1 and KCNIP4. Genomic regions overlapping both FST and ROH harbor genes related to immunity (IL4R, PHF23, GABARAP, GPS2, and CD68), reproduction (SPATA2L, TNFSF12, TMEM95, and RNF17), embryonic development (TCF25 and SOX15) and adaptation (MC1R, KDR, and KIT), suggesting potential genetic adaptations to local environmental conditions. Our results contribute to the understanding of the genetic architecture of different goat breeds and may provide valuable information for effective preservation and breeding programs of local goat breeds in Egypt.

Sliding window haplotype approaches overcome single SNP analysis limitations in identifying genes for meat tenderness in Nelore cattle.

BACKGROUND: Traditional single nucleotide polymorphism (SNP) genome-wide association analysis (GWAA) can be inefficient because single SNPs provide limited genetic information about genomic regions. On the other hand, using haplotypes in the statistical analysis may increase the extent of linkage disequilibrium (LD) between haplotypes and causal variants and may also potentially capture epistastic interactions between variants within a haplotyped locus, providing an increase in the power and robustness of the association studies. We performed GWAA (413,355 SNP markers) using haplotypes based on variable-sized sliding windows and compared the results to a single-SNP GWAA using Warner-Bratzler shear force measured in the longissimus thorasis muscle of 3161 Nelore bulls to ascertain the optimal window size for identifying the genomic regions that influence meat tenderness. RESULTS: The GWAA using single SNPs identified eight variants influencing meat tenderness on BTA 3, 4, 9, 10 and 11. However, thirty-three putative meat tenderness QTL were detected on BTA 1, 3, 4, 5, 8, 9, 10, 11, 15, 17, 18, 24, 25, 26 and 29 using variable-sized sliding haplotype windows. Analyses using sliding window haplotypes of 3, 5, 7, 9 and 11 SNPs identified 57, 61, 42, 39, and 21% of all thirty-three putative QTL regions, respectively; however, the analyses using the 3 and 5 SNP haplotypes, cumulatively detected 88% of the putative QTL. The genes associated with variation in meat tenderness participate in myogenesis, neurogenesis, lipid and fatty acid metabolism and skeletal muscle structure or composition processes. CONCLUSIONS: GWAA using haplotypes based on variable-sized sliding windows allowed the detection of more QTL than traditional single-SNP GWAA. Analyses using smaller haplotypes (3 and 5 SNPs) detected a higher proportion of the putative QTL.

Characterization of genomic regions escaping epigenetic reprogramming in sheep.

The mammalian genome undergoes two global epigenetic reprogramming events during the establishment of primordial germ cells and in the pre-implantation embryo after fertilization. These events involve the erasure and re-establishment of DNA methylation marks. However, imprinted genes and transposable elements (TEs) maintain their DNA methylation signatures to ensure normal embryonic development and genome stability. Despite extensive research in mice and humans, there is limited knowledge regarding environmentally induced epigenetic marks that escape epigenetic reprogramming in other species. Therefore, the objective of this study was to examine the characteristics and locations of genomic regions that evade epigenetic reprogramming in sheep, as well as to explore the biological functions of the genes within these regions. In a previous study, we identified 107 transgenerationally inherited differentially methylated cytosines (DMCs) in the F1 and F2 generations in response to a paternal methionine-supplemented diet. These DMCs were found in TEs, non-repetitive regions, and imprinted and non-imprinted genes. Our findings suggest that genomic regions, rather than TEs and imprinted genes, have the propensity to escape reprogramming and serve as potential candidates for transgenerational epigenetic inheritance. Notably, 34 transgenerational methylated genes influenced by paternal nutrition escaped reprogramming, impacting growth, development, male fertility, cardiac disorders, and neurodevelopment. Intriguingly, among these genes, 21 have been associated with neural development and brain disorders, such as autism, schizophrenia, bipolar disease, and intellectual disability. This suggests a potential genetic overlap between brain and infertility disorders. Overall, our study supports the concept of transgenerational epigenetic inheritance of environmentally induced marks in mammals.

Effects of paternal methionine supplementation on sperm DNA methylation and embryo transcriptome in sheep.

Environmental effects on gene expression and offspring development can be mediated by epigenetic modifications. It is well established that maternal diet influences DNA methylation patterns and phenotypes in the offspring; however, the epigenetic effects of paternal diet on developing offspring warrants further investigation. Here, we examined how a prepubertal methionine-enriched paternal diet affected sperm DNA methylation and its subsequent effects on embryo gene expression. Three treatment and three control rams were bred to seven ewes, and blastocysts were flushed for RNA extraction. Semen was collected from all rams and submitted for reduced representation bisulfite sequencing analysis. In total, 166 differentially methylated cytosines were identified in the sperm from treatment versus control rams. Nine genes were found to be differentially expressed in embryos produced from treatment versus control rams, and seven differentially methylated cytosines in the sperm were found to be highly correlated with gene expression in the embryos. Our results demonstrate that sperm methylation differences induced by diet may influence fetal programming.

Paternal diet induces transgenerational epigenetic inheritance of DNA methylation signatures and phenotypes in sheep model.

Transgenerational epigenetic inheritance (TEI) requires transmission of environmentally induced epigenetic changes and associated phenotypes to subsequent generations without continued exposure to the environmental factor that originated the change. TEI is well-established in plants and Caenorhabditis elegans; however, occurrence in mammals is debated and poorly understood. Here, we examined whether paternal diet from weaning to puberty-induced changes in sperm DNA methylation that were transmitted to subsequent generations. Over 100 methylated cytosines, environmentally altered in the F0 generation, were inherited by the F1 and F2 generations. Furthermore, the F0 paternal diet was associated with growth and male fertility phenotypes in subsequent generations. Differentially methylated cytosines were correlated with gene expression. Our results demonstrate that some sperm methylation sites may escape DNA methylation erasure and are transmitted to subsequent generations despite the 2 waves of epigenetic programming: in primordial germ cells and in embryos after fertilization. These results advance our understanding of the complex relationships between nature and nurture.

Genome-wide association analyses identify genotype-by-environment interactions of growth traits in Simmental cattle.

Understanding genotype-by-environment interactions (G × E) is crucial to understand environmental adaptation in mammals and improve the sustainability of agricultural production. Here, we present an extensive study investigating the interaction of genome-wide SNP markers with a vast assortment of environmental variables and searching for SNPs controlling phenotypic variance (vQTL) using a large beef cattle dataset. We showed that G × E contribute 10.1%, 3.8%, and 2.8% of the phenotypic variance of birth weight, weaning weight, and yearling weight, respectively. G × E genome-wide association analysis (GWAA) detected a large number of G × E loci affecting growth traits, which the traditional GWAA did not detect, showing that functional loci may have non-additive genetic effects regardless of differences in genotypic means. Further, variance-heterogeneity GWAA detected loci enriched with G × E effects without requiring prior knowledge of the interacting environmental factors. Functional annotation and pathway analysis of G × E genes revealed biological mechanisms by which cattle respond to changes in their environment, such as neurotransmitter activity, hypoxia-induced processes, keratinization, hormone, thermogenic and immune pathways. We unraveled the relevance and complexity of the genetic basis of G × E underlying growth traits, providing new insights into how different environmental conditions interact with specific genes influencing adaptation and productivity in beef cattle and potentially across mammals.

Selection signatures in candidate genes and QTL for reproductive traits in Nellore heifers.

The identification of selection signature genes may help to detect genomic regions that underwent artificial selection and contributed to phenotypic diversity. The aim of this study, therefore, was to detect selection signatures in candidate genes and quantitative trait locus (QTL) for reproductive traits in a Nellore population being selected for sexual precocity. A total of 2035 Nellore heifers, sourced from breeding programs focused on sexual precocity, were used. Candidate genes and some specific QTL related to reproductive traits were chosen based on published literature and Animal QTL databases, respectively, for investigation whether these regions were affected by selection. Selection signature DNA sequences were detected in the selected regions using the extended haplotype homozygosity (EHH) and relative extended haplotype homozygosity (REHH) methods. From 22,241 single nucleotide polymorphisms (SNPs) located in the candidate genes and QTL, 17,312 SNPs generated 2756 haplotype blocks. A total of 7518 EHH tests were analyzed using haplotypes with a frequency of more than 25%, for which there were 39 tests that were significant for REHH (P<0.01). Selection signature DNA sequences were detected that contained several QTLs for important reproductive traits in cattle, suggesting that reproductive traits may have been affected by selection for sexual precocity in this population. Forty-six genes were located in the selection signature regions, whereas 24 genes participated in important biological processes or pathways that may underlie sexual precocity. These results indicate there are possible molecular mechanisms related to sexual precocity in the Nellore breed.

Genetic analysis of carcass and meat quality traits in Nelore cattle1.

The objective of this study was to estimate genetic parameters for carcass and meat quality traits, as well as their genetic correlations using pedigree and genomic information. A total of 3,716; 3,702; 3,439; 3,705; and 3,714 records of 12th-13th rib LM area (LMA), backfat thickness (BF), HCW, marbling score (MARB), and Warner-Bratzler peak shear force (WBSF), respectively, were used. Animals were genotyped with BovineHD BeadChip and GeneSeek Genomic Profiler Indicus HD - GGP75Ki panel. The (co)variance components were estimated by Bayesian inference using a multitrait ssGBLUP analysis. The animal model included fixed effects of contemporary group (defined by the combination of farm and year of birth, and management group at yearling) and age of animal at slaughtering as a covariate (linear). Direct additive genetic and residual effects were fitted as random. The posterior means and SD of heritabilities for LMA, BF, HCW, MARB, and WBSF were 0.28 (0.03), 0.21 (0.04), 0.21 (0.04), 0.12 (0.04), and 0.11 (0.03), respectively. The posterior means for genetic correlations between LMA and meat quality were positive and moderate with MARB (0.38 ± 0.12) and negative with WBSF (-0.47 ± 0.12). Low genetic correlations were estimated between BF and WBSF (-0.03 ± 0.16) and between HCW and MARB (-0.04 ± 0.14), indicating that these traits are not controlled by the same set or linked genes. Carcass traits (LMA, BF, and HCW) presented moderate heritability providing quick response to the selection purpose. The estimates of heritability for meat quality traits (MARB and WBSF) were low and indicate that the rate of genetic improvement for these traits would be slow. Genetic correlations indicated that selection for carcass traits would not be strongly antagonistic for improving meat quality.

Association of ADIPOQ, OLR1 and PPARGC1A gene polymorphisms with growth and carcass traits in Nelore cattle.

In beef cattle farming, growth and carcass traits are important for genetic breeding programs. Molecular markers can be used to assist selection and increase genetic gain. The ADIPOQ, OLR1 and PPARGC1A genes are involved in lipid synthesis and fat accumulation in adipose tissue. The objective of this study was to identify polymorphisms in these genes and to assess the association with growth and carcass traits in Nelore cattle. A total of 639 animals were genotyped by PCR-RFLP for rs208549452, rs109019599 and rs109163366 in ADIPOQ, OLR1 and PPARGC1A gene, respectively. We analyzed the association of SNPs identified with birth weight, weaning weight, female yearling weight, female hip height, male yearling weight, male hip height, loin eye area, rump fat thickness, and backfat thickness. The OLR1 marker was associated with rump fat thickness and weaning weight (P < 0.05) and the PPARGC1 marker was associated with female yearling weight.