Animal genetics最新文献

Camels possess exceptional adaptability, allowing them to withstand extreme temperatures in desert environments. They conserve water by reducing their metabolic rate and regulating body temperature. The heart of the camel plays a crucial role in this adaptation, with specific genes expressed in cardiac tissue that are essential for mammalian adaptation, regulating cardiac function and responding to environmental stressors. One such gene, nebulin-related-anchoring protein (NRAP), is involved in the assembly of myofibrils and the transmission of force within the heart. In our study of the NRAP gene across various livestock species, including three camel species, we identified a camel-specific exon region in the NRAP transcripts. This additional exon (exon 4) contains an open reading frame predicted in camels. To investigate its function, we generated knock-in mice expressing camel NRAP exon 4. These 'camelized mice' exhibited normal phenotypic characteristics compared with wild-type mice but showed elevated body temperatures under cold stress. Transcriptome analyses of the hearts from camelized mice under cold stress revealed differentially expressed inflammatory cytokine genes, known to influence cardiac function by modulating the contractility of cardiac muscle cells. We propose further investigations utilizing these camelized mice to explore these findings in greater depth.

Sheep have naturally pigmented wool which interferes with dyeing. Selection has been carried out over many years to remove pigment, with substantial success, but most wool still contains some pigment. As an alternative to selection, it has been proposed to take a naturally occurring mutation found in black Suffolk sheep, that blocks wool pigmentation, and introgress it into other breeds. However, the nature of the mutation has not been identified, prompting us to characterise it. The Suffolk white-fleece phenotype is associated with a novel 3-bp deletion in the gene SLC45A2, which encodes a membrane bound transporter that mediates melanin synthesis. The deletion results in the removal of one amino acid from the protein. The assignment of this deletion as the likely causative mutation is supported by it: being homozygous in the genome of nine animals with a white fleece and not homozygous in the genomes of eight animals with a black fleece; having a high level of conservation of the encoded amino acid sequence in the region surrounding the deleted amino acid across Mammalia; and the same deletion (but in a compound heterozygous state) being found in human SLC45A2 in a person with albinism.

The intramuscular oleic-to-stearic fatty acid ratio (C18:1n-9/C18:0) is an important indicator of the biosynthesis and desaturation of fatty acids in muscle. By using an RNA-Seq approach in muscle samples from 32 BC1_DU (25% Iberian and 75% Duroc) pigs with divergent values (high: H and low: L) of C18:1n-9/C18:0 fatty acids ratio, a total of 81 differentially expressed genes (DEGs) were identified. Functional analyses of DEGs indicate that mainly peroxisome proliferator-activated receptor signaling pathway (associated genes: PPARG, SCD, PLIN1, and FABP3) was overrepresented. Notably, SCD is directly involved in the conversion of C18:0 to C18:1n-9, and PPARG is a transcription factor regulating lipid metabolism genes, including SCD. However, other DEGs (e.g., ACADVL, FADS3, EPHB2, HGFAC, NGFR, NR0B2, MDH1, MMAA, PPP1R1B, SFRP5, RAB30, and TRARG1) are plausible candidate genes to explain the phenotypic differences of the C18:1n-9/C18:0 ratio. Interestingly, seven genetic variants within the SCD (including the well-known AY487830:g.2228T>C SNP and other novel genotyped polymorphisms) are associated with two haplotypes. Although the haplotypes are segregating at different frequencies in the H and L groups, they do not fully explain the desaturation ratios or the SCD expression levels. A more complex model, including polyunsaturated fatty acids such as C18:2n-6, C20:4n-6, and C18:3n-3, is suggested to explain the regulation of the C18:1n-9/C18:0 desaturation ratio in porcine muscle.

Congenital malformations in cattle pose a diagnostic challenge with limited treatment options and are often associated with a guarded prognosis. The aim of this study was to characterize the clinicopathological phenotype of a viable calf with complex congenital heart defects and carpus valgus, and to identify a possible genetic cause using a whole genome sequencing trio approach. A 3-month-old female Holstein calf was referred for respiratory distress and congenital carpal deviation. Clinicopathologic findings included ventricular septal defect, ventricular dilatation, atrioventricular valve dysplasia, an overriding aorta, and unilateral carpus valgus. Genetic analysis revealed a private heterozygous missense variant in BRI3BP affecting an evolutionarily conserved residue (c.478G>A; p.Val160Ile). The variant was predicted to be deleterious and was present only in the affected calf and was absent in more than 5100 sequenced bovine genomes, including both parents, indicating a de novo origin. This study implicates an important role for the uncharacterized BRI3 binding protein in cardiac and possibly also bone development. By presenting the first BRI3BP-related disease model, this study demonstrates the potential to gain new insights into the function of individual genes by using phenotypically well-studied spontaneous mutants in large animals, and it provides a novel candidate gene for similar conditions in humans.

Domesticated sheep have adapted to contrasting and extreme environments and continue to play important roles in local community-based economies throughout Africa. Here we review the Neolithic migrations of thin-tailed sheep and the later introductions of fat-tailed sheep into eastern Africa. According to contemporary pictorial evidence, the latter occurred in Egypt not before the Ptolemaic period (305-25 BCE). We further describe the more recent history of sheep in Egypt, the Maghreb, west and central Africa, central-east Africa, and southern Africa. We also present a comprehensive molecular survey based on the analysis of 50 K SNP genotypes for 59 African breeds contributed by several laboratories. We propose that gene flow and import of fat-tailed sheep have partially overwritten the diversity profile created by the initial migration. We found a genetic contrast between sheep north and south of the Sahara and a west-east contrast of thin- and fat-tailed sheep. There is no close relationship between African and central and east Asian fat-tailed breeds, whereas we observe within Africa only a modest effect of tail types on breed relationships.

Feed efficiency (FE) in pigs is an important factor in the profitability of pig farming operations. It refers to the ability of a pig to convert the feed it consumes into body weight. We used two metrics to measure FE: feed conversion ratio and average daily residual feed intake. A previous genome-wide association study and transcriptome study in crossbred pigs identified two QTL regions on SSC9 associated with residual feed intake and pointed out two candidate genes of interest: (a) the gene encoding the Aryl Hydrocarbon Receptor gene (AHR) transcription factor; and (b) the Dynein, Axonemal, Heavy Polypeptide 11 gene (DNAH11). The previous study identified missense mutations in both genes leading to a conservative substitution of glycine to cysteine in AHR (AHR_rs339939442) and two non-conservative substitutions in DNAH11, where arginine is replaced by threonine (DNAH11_rs325475644) and alanine is replaced by threonine (DNAH11_rs346074031). We have now genotyped the missense mutations in independent cohorts of 107 Duroc, 155 Landrace and 160 Yorkshire pigs to substantiate further if these variants directly impact FE-related phenotypes. We verified that allele T of AHR_rs339939442 in AHR improves FE in Yorkshire pigs. Genotype GG of AHR_rs339939442 was fixed in Duroc pigs. We also confirmed that the variants rs325475644 and rs346074031 in DNAH11 did not affect FE. The findings contribute valuable insights into the genetic mechanisms governing FE in pigs, potentially offering contributions for future enhancements of FE.

Hypospadias occurs sporadically in male livestock and is characterized by a non-fused urethra during fetal development. In this study, perineal hypospadias, a bifid scrotum, penile hypoplasia, and bilateral abdominal cryptorchidism were diagnosed in a neonatal Holstein male calf. Septicemia was also suspected due to hypothermia, blurred conjunctivae, and loss of sucking and swallowing reflexes. Gross pathology revealed that both testicles were located intraabdominally caudally to the kidneys. Histopathological examination of the hypospadias showed a urothelium-lined mucosal fold and parts of the corpus cavernosum penis and prepuce in the subcutis. Whole genome sequencing was performed on the affected calf. Analysis of short-read coverage depth along the chromosomes identified an entire extra copy of chromosome 26. Based on the comparison of available variant calling data from the sire, the identified trisomy 26 is due to non-disjunction of homologous chromosomes during the generation of paternal gametes. We have shown for the first time an association between bovine hypospadias and trisomy 26, which adds to the understanding of variation in fetal male sexual development.

The reproductive characteristics of Hanwoo play a significant role in farm profitability by decreasing the generation interval. This study analyzed 1015 primiparous and 916 multiparous cows using a genome-wide association study with both single-locus (GEMMA, GCTA) and multi-locus models (FarmCPU, BLINK). A significant marker for age at first service was identified across all methods. For age at first conception, GEMMA identified two markers, while FarmCPU and BLINK identified 14 and two markers, respectively. Regarding age at first calving, GEMMA identified two markers, and FarmCPU and BLINK found 15 and two markers, respectively. In multiparous cows, except for days open, one marker for gestation length and two markers for calving interval were identified in the multi-locus models (FarmCPU and BLINK). Additionally, one marker for the number of services per conception was identified using GEMMA. Key candidate genes included PLCB1 (maintaining pregnancy), MUC1 (fetal development), and ADCY5 (associated with fetal birth), while TXNL1 regulates embryo implantation timing. Gene ontology functions associated with embryo implantation and placental regulation were also confirmed (GO:0046875). Although the multi-locus models identified a greater number of markers and candidate genes, there was no overlap with the results from the single-locus models. The multi-locus models showed enhanced detection power, but slight inflation in test statistics (λ values) necessitates cautious interpretation to avoid false positives. Thus, a combination of both models is recommended to improve reproductive efficiency in cows, providing valuable insights into the genetic aspects of reproductive traits.

Short tandem repeats (STRs) are abundant and have high mutation rates across cattle genomes; however, comprehensive exploration of cattle STRs is needed. Here, we constructed a comprehensive map of 467 553 polymorphic STRs (pSTRs) constructed from 423 cattle genomes representing 59 breeds worldwide. We observed that pSTRs in coding sequences and 5′UTRs (Untranslated Regions) were under strong selective constraints and exhibited a relatively low level of diversity. Furthermore, we found that these pSTRs underwent more contraction than expansion. Population analysis showed a strong positive correlation (R = 1) between pSTR diversity and single nucleotide polymorphic heterozygosity. We also investigated STR differences between taurine and indicine cattle and detected 2301 highly divergent STRs, which might relate to immune, endocrine and neurodevelopmental pathways. In summary, our large-scale study characterizes the spectrum of STRs in cattle, expands the scale of known cattle STR variation and provides novel insights into differences among various cattle subspecies.

North Africa counts several sheep breeds that can be categorized as fat- and thin-tailed. The former are well adapted to dryland environments. In this study, we used 50K genome-wide single nucleotide polymorphism profiles from 462 animals representing nine fat-tailed and 13 thin-tailed sheep breeds across North Africa to localize genomic regions putatively under differential selective pressures between the two types of breeds. We observed genetic clines from east to west and from north to south. The east–west cline separates the fat- and thin-tailed breeds, with the exception of the fat-tailed Algerian Barbarine, which is closely related to a genetically homogeneous cluster of Moroccan and Algerian thin-tailed breeds. Using a combination of three extended haplotype homozygosity tests, we detected seven candidate regions under divergent selection between fat- and thin-tailed sheep. The strongest selection signals reside on chromosomes 1 and 13, with the latter spanning the BMP2 gene, known to be associated with the fat-tail phenotype. Overall, the candidate regions under selection in fat-tailed sheep overlap with genes associated with adaptation to desert-like environments including adipogenesis, as well as heat and drought tolerance. Our results confirm previously reported candidate genes known to be a target of fat-tail selection in sheep but also reveal novel candidate genes specifically under selection in North African populations.