Animal genetics最新文献

This study investigates autosome evolution between river buffalo (Bubablus bubalis, BBU) and cattle (Bos taurus, BTA), two closely related species within the Bovidae family. Despite differences in chromosome numbers (2n = 60 in cattle and 2n = 50 in river buffalo), previous cytogenetic studies have shown high autosome similarity. However, standard banding techniques have limitations in detecting small-scale genomic rearrangements. Using molecular comparisons, this study identifies two previously undetected chromosomal inversions: a 30-Mb inversion on BBU7 (compared to BTA6) and a 4-Mb inversion on BBU14 (compared to BTA13). These findings were validated through bioinformatics analyses (genomic alignments and BLAST searches) and confirmed via fluorescence in situ hybridization technique. In addition, it has been shown that several river buffalo chromosomes are shown inverted in the genome assembly considered in this study (NDDB_SH_1). The study highlights that autosome evolution in Bovidae involves not only centric fusions but also cryptic intra-chromosomal rearrangements. These results contribute to a deeper understanding of genome evolution in closely related species and demonstrate the importance of high-resolution molecular techniques in uncovering hidden genomic changes.

We recently described several major-effect recessive loci impacting anatomical and lactation traits in dairy cattle. Two of these loci in particular presented multiple candidate causative variants, comprising tightly linked coding variants that could not be easily differentiated on a statistical or functional basis. Here, we re-examine the candidacy of these variants by leveraging a dataset of 1 million genotyped animals. Assessing lactation and bodyweight effects in conjunction with rare, recombined genotypes for the IL4R, KIAA0556, ITGAL, DPF2, and MUS81 candidates, we highlight ITGAL and MUS81 as the most likely causative genes for the two QTL. Recombinant homozygotes for these genes present larger, more significant effects than other candidates at the same loci, with both representing premature stop mutations anticipated to inactivate ITGAL and MUS81. We further examined homozygotes for the ITGAL mutation to better understand the range of phenotypes impacted. While outwardly normal, ITGAL mutants showed significant differences in the number and composition of circulating leukocytes, consistent with the role of ITGAL as a key mediator of leukocyte signalling, adhesion, and migration. These results demonstrate how near-perfectly linked candidate mutations can be differentiated given population-scale data, and highlight the ITGAL and MUS81 mutations as diagnostic targets to help manage the frequency of these variants.

Atherosclerosis, a chronic inflammatory vascular disease driven by the accumulation of low-density lipoprotein-derived cholesterol on arterial walls, is the leading cause of mortality in humans worldwide but is rare in animals. We recently identified spontaneous atherosclerosis in the Korat cat breed, characterized by severe hypercholesterolemia and clinical signs of congestive heart failure, ultimately leading to death. Histopathological examination revealed lesions similar to those observed in human atherosclerosis. Given the close genetic relationship among affected cats, we hypothesized a genetic basis for the condition. We employed whole genome sequencing of a trio (one case and its parents) to identify genetic variants associated with the condition. We identified a homozygous XM_003981898.6:c.2406G>A variant specific to the cases in the LDLR gene. This variant is predicted to result in a premature stop codon, XP_003981947.3:p.(Trp758*), leading to a truncated LDLR protein that lacks the last 108 amino acids, including the transmembrane and intracellular C-terminal domains. Genotyping this LDLR variant in a cohort of 309 Korat cats confirmed its segregation and revealed new homozygous cats for clinical follow-up. In silico analyses demonstrated that the identified variant appears optimal for gene-editing-based therapeutics. In conclusion, we have described cats with a truncating LDLR defect. Given that PCSK9, another known hypercholesterolemia gene, has been lost in cats during evolution, our study is likely to provide an exciting double knockout model for human atherosclerosis research and therapeutics.

Testicular disorders of sex development (DSD) in cats with XX sex chromosomes and the absence of the SRY gene are rare congenital abnormalities. A Maine Coon tomcat with a normal penis, gonads in the scrotum, low serum testosterone concentration, and an elevated level of anti-Müllerian hormone (AMH) was subjected to genetic analyses due to an unusual tortoiseshell coat color for males. Primary studies revealed the presence of XX sex chromosomes, the lack of SRY and the presence of two copies of the candidate SOX9. The DSD tomcat and its parents were analyzed using whole genome sequencing. Candidate SNPs in AMH, ORC1, DOCK8, PRKAR1A, and TMEM186 genes, as well as a known intronic 5-kb deletion in X-linked ARHGAP36 gene, which is responsible for orange coat, were identified. Potentially pathogenic homozygous genotypes were observed in all candidate genes; however, only in AMH and ORC1 were these genotypes rare in a control cohort. Further studies were focused on two SNPs located in the 5′-and 3′-untranslated regions (UTRs) of AMH. It has been experimentally demonstrated that only a short AMH transcript is present in feline testes. In silico analysis revealed that the SNP located in the 3′UTR of AMH occurs within a sequence that partially matches the canonical binding site for human miR-5571-5p. This microRNA is expressed in mammalian testes, which we confirmed in feline testicular tissue. We concluded that SNP in the 3′UTR of AMH is associated with elevated expression of the encoded hormone; however, it is not the cause of the testicular DSD phenotype in the studied Maine Coon tomcat.

Teat number is an economically important trait in pigs because it is relevant to reproduction efficiency and thus production profitability. In this study, a genome-wide association study (GWAS) was performed with genotyping by genome resequencing, which identified six significant SNPs (single nucleotide polymorphisms) on Sus scrofa chromosome 2 (SSC2) and SSC7 for total teat number using 888 Large White × Tongcheng crossbred pigs. The Bayesian fine-mapping further defined two QTL (quantitative trait loci) with locations of 18.32–19.08 and 21.18–22.11 Mb on SSC2, and one QTL spanned an interval of 97.14–97.91 Mb on SSC7, respectively. The first SSC2 QTL region harbors four candidate genes TTC17, API5, miR-129-2 and HSD17B12. The SSC7 QTL region include two reported candidate genes, VRTN and ABCD4. The average teat numbers are 12.42 ± 1.38, 13.52 ± 1.10 and 13.87 ± 1.03 for TT, TA and AA genotypes of rs340400902 on SSC2, respectively. The T allele of rs340400902 on SSC2 in Large White × Tongcheng crossbred pigs was found to originate from Tongcheng pigs. These findings provides SNPs and candidate genes for the genetic improvement of teat number in pigs.

There are significant differences in fat deposition capacity in muscle among different pig breeds, and such differences may be affected by the regulation of gene expression. Comparison of gene expression differences in intramuscular fat (IMF) content in the longissimus dorsi muscle of different pig breeds by RNA sequencing can reveal important genes and pathways related to IMF content and provide theoretical support for meat quality improvement and genetic breeding. In this study, 11 863 expressed genes were identified in six different pig breeds in total, and 2774 differentially expressed genes were identified between high-IMF and low-IMF groups, of which ADAMTS8 was significantly differentially expressed across all six breeds. Based on these data, an enrichment analysis was performed, and the Kyoto Encyclopedia of Genes and Genomes pathways closely related to IMF content were found to be PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, and extracellular matrix–receptor interaction; the PI3K-Akt signaling pathway is especially closely related to muscle development and fat deposition. Analysis of differentially expressed genes in the PI3K-Akt signaling pathway by protein–protein interaction network showed that EGFR, EGF, ITGB3, IGF1, FGF2, and PDGFA are the key genes related to IMF content. These findings can not only contribute to understanding of the genetic regulation of IMF, but also provide scientific basis for future pork quality improvement and breeding strategies.

Brown bears (Ursus arctos) and black bears (Ursus thibetanus) are important species on the Qinghai-Xizang Plateau. However, limited studies have been conducted on these species due to sampling constraints. This study, using 16S rRNA amplicon sequencing and untargeted metabolomics, analyzed fecal samples from six wild brown bears and six wild black bears. The results revealed distinct gut microbiota profiles, with brown bears showing higher microbial richness, particularly in Proteobacteria, Bacteroidota, and Actinobacteriota, while black bears were mainly enriched in Firmicutes. Lipid metabolism emerged as the primary metabolic pathway for both species, probably aiding adaptation to the plateau environment. Notably, we found positive correlations between differential metabolites and specific microbiota; in addition, traces of pesticides suggested contamination in the region. Our study provides valuable insights into the gut microbial diversity and metabolomic features of wild brown bears and black bears from the Qinghai-Xizang Plateau, contributing to our understanding of wildlife ecology in this unique environment.

Early genetic studies have suggested that body size in rabbits can be considered a quantitative trait. Several rabbit breeds can be distinguished based on body size, including a few dwarf breeds differentiated by other morphological characteristics. While a large deletion in the HMGA2 gene is a major locus associated with dwarfism in Netherland Dwarf rabbits, it may not fully explain the reduced body size in this breed or other dwarf breeds. In this study, we compared the genomes of two dwarf rabbit breeds (Dwarf Lop and Netherland Dwarf) with those of non-dwarf rabbits by analysing whole-genome sequencing data obtained using a DNA-pool sequencing approach. We applied the fixation index (F_ST) and pooled heterozygosity (H_P) statistics to identify signatures of selection related to small body size by contrasting dwarf with non-dwarf breeds and comparing dwarf breeds. We identified several genomic regions that contain genes previously linked to body dimensions in various species, including LCORL-NCAPG, COL2A1, GHRHR and CENPE. Functional enrichment analysis of genes within the top differentiated regions revealed biological terms related to skeletal development, further supporting the biological relevance of these loci. Additionally, the use of the latest version of the reference rabbit genome enabled the identification of a genomic region containing FGFR3, a gene linked to achondroplasia. Some genomic regions showed differentiation between the two dwarf breeds, suggesting that their small body size may, in part, arise through different genetic mechanisms. Overall, these findings support a polygenic architecture underlying small size in rabbits, influenced by a few major loci.

Fragile foal syndrome (FFS) is a disease caused by a recessive lethal missense mutation in the PLOD1 gene located on ECA2. Despite its harmful effect, a relatively high frequency of FFS carriers was observed in Warmblood breeds spanning from 7.4% in a random sample of Swedish Warmblood breed to 17% in the Hanoverian and Danish Warmblood, indicating potential heterozygous advantage. Balancing selection can be further studied based on haplotype blocks and via detection of heterozygosity-rich region (ROHet) around the target of selection. In this study we evaluated the presence of haplotype blocks and ROHet on ECA2 in 380 Swedish Warmblood horses. We compared the results of ROHet with the rest of the genome. On average, 11.7 heterozygosity rich regions were identified per horse on ECA2, with no significant difference in numbers and length compared to what was found in other chromosomes. A unique haplotype block containing 28 markers was found in the FFS haplotype, while there were several haplotype blocks in the non-carrier haplotype. This unique haplotype block mostly spanned the region upstream of the PLOD1 gene and included the MFN2 gene. The presence of this extended haplotype, shared by multiple individuals and including both the FFS variant and the MFN2 gene, suggests that this region may be under selection. While we did not find a clear heterozygosity-rich region around the FFS variant, the extended haplotype may reflect either a signature of balancing selection or linkage disequilibrium with a positively selected variant in MFN2, PLOD1, or nearby loci.