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Proteomic signatures of mitochondrial dysfunction associated with atrial fibrillation in goats.

Atrial fibrillation (AF) increases energy demand in atrial myocytes, yet the mitochondrial mechanisms underlying this stress remain poorly defined. Using previously published proteomic data from left atrial tissue of AF and sham-operated goats, we performed organelle-specific bioinformatic analyses of the mitochondrial fraction. Over-representation and consensus pathway analyses consistently highlighted enrichment of oxidative phosphorylation (OXPHOS) subunits. Gene set enrichment and network analyses implicated Heat Shock Protein Family A Member 9 (HSPA9) as a potentially central regulatory hub coordinating the dysregulation of Complex I and III subunits, with 69% of regulatory relationships showing pathway concordance. These results indicate a coordinated, system-wide mitochondrial adaptation in AF, integrating energy production, proteostasis, and respiratory chain regulation.

Animals

Genomic signatures of dairy adaptation in Saccharomyces cerevisiae from traditional Yaghnob goat-cheese fermentation.

The growing interest in studying Saccharomyces cerevisiae strains from previously unexplored niches is greatly expanding our understanding of this yeast's ecology and evolution. While strains involved in alcoholic fermentation are the most studied, S. cerevisiae has also been isolated from milk fermentations and their products, suggesting a potential evolutionary specialization for dairy environments. These fermentations are characterized by the predominant presence of lactose, a carbon source that S. cerevisiae cannot metabolize directly but can exploit through the enzymatic activity of co-occurring microorganisms that convert lactose into fermentable substrates, such as glucose and galactose. In this study, we analyzed S. cerevisiae strains isolated from an unexplored and remote niche: traditional goat fermented milk produced by the Yaghnob people, an ethnically and geographically partly isolated population living in the Upper Zarafshan area of the Republic of Tajikistan. Comparative analyses with published S. cerevisiae genomes positioned the Yaghnob strains at the base of the phylogenetic dairy clade. These strains revealed distinctive coding sequences and strain-specific single-nucleotide variants present in all Yaghnob strains but absent from the other 1,053 strains analyzed. Further investigation of variants in key genes involved in galactose metabolism provided insights into the genomic and protein-level evolution of Yaghnob strains, uncovering unique genomic signatures of adaptation to the dairy environment.

Saccharomyces cerevisiae

Metagenomics reveals cryptic circulation of zoonotic viruses in Nigeria.

Zoonotic spillover events pose an ongoing threat to global health, with historic and recent viral diseases of international concern emerging from animal reservoirs 1-6. In Nigeria, limited surveillance of animal hosts at the human and animal interface continues to hinder our understanding of viruses that are cryptically circulating in animals near human dwellings with potential for consequential spillover events. We performed unbiased metagenomic next-generation sequencing (mNGS) on tissue and swab samples collected from 240 individual animals across 11 taxa (rodents, shrews, bats, goats, sheep, pigs, dogs, cats, chickens, cattle egrets, and lizards) in two Lassa-affected Nigerian states (Ondo and Ebonyi). Host-depleted sequencing reads were assembled into contigs, taxonomically classified, and subjected to phylogenetic analyses to characterize viral diversity, host associations, and evidence of cross-species transmission. Across all samples, we identified 214 distinct viral taxa spanning 33 families, of which 41% (n = 83) represent novel species by ICTV criteria. Positive-sense RNA viruses dominated (Coronaviridae, Picornaviridae, Astroviridae), followed by negative-sense RNA, single- and double-stranded DNA, and double-stranded RNA viruses. Notably, human-associated enteroviruses-including Hepatitis A virus (genotype 1b), echoviruses, coxsackieviruses, and noroviruses-were detected in goats, pigs, dogs, and chickens, indicating cryptic circulation of human pathogens in peridomestic and domesticated animals. Phylogenetic reconstructions revealed multiple cross-species viral sharing events, particularly among rodents, goats, sheep, and pigs, and extensive recombination within Nigerian Betacoronavirus 1 lineages. Interestingly we found a putative novel avian like coronavirus in rodents, goats and sheep. Ecological modelling demonstrated that host species identity, sample type, and sampling effort were primary drivers of viral richness and abundance, and that higher overall viral diversity strongly predicted cross-species transmission potential. Our integrated mNGS approach uncovered a rich and dynamic virome within animals inhabiting human-dominated environments in Nigeria, including undetected circulation of human enteric viruses. These findings underscore the importance of broad-taxonomic, real-time surveillance at human-animal interfaces to inform early-warning systems and pandemic preparedness, particularly in low-resource settings.

Journal Article

Validation of caprine H11 and the Rosa26 platform for transgene integration via CRISPR-based system: investigations on stable transgene expression and genetic biosafety.

CRISPR/Cas9 technology is an efficient tool for site-specific livestock gene editing. However, to minimize potential disruption of host genome function, exogenous genes should be integrated into well-characterized genomic loci, such as H11 or Rosa26, which have been empirically validated for stable transgene expression. This study established a multi-dimensional assessment system to evaluate the biological applicability of the H11 locus and the widely used Rosa26 targeting platform as sites for targeted integration of exogenous genes in goats. Donor cells carrying the enhanced green fluorescent protein (EGFP) reporter gene at the H11 and Rosa26 loci were generated via CRISPR/Cas9-mediated homology-directed repair; this was followed by somatic cell nuclear transfer to produce transgenic cloned embryos and healthy offspring. Multi-dimensional analyses revealed the following. At the cellular level, there was stable and efficient EGFP expression at integration sites, with donor cells maintaining normal cell cycle progression, proliferation capacity, and apoptosis levels, and with no alterations in the transcriptional integrity of adjacent genes. At the embryonic level, there was sustained EGFP expression across pre-implantation embryonic stages, with developmental metrics statistically indistinguishable from wild-type embryos. Finally, at the individual level, cloned offspring exhibited growth phenotypes consistent with wild-type counterparts, and EGFP showed broad-spectrum expression in eight tissues. This study establishes the first CRISPR/Cas9-based crossscale (cellular-embryonic-individual) validation in goats, demonstrating that the H11 and Rosa26 loci support efficient and stable transgene integration in goats. These results provide a precise and predictable technical framework for livestock genetic improvement.

Animals

Hemotropic mono- and coinfections in Colombian ruminants: descriptive occurrence and host-related factors associated with coinfection in cattle.

Hemotropic pathogens such as Anaplasma, Babesia, Mycoplasma, and Trypanosoma are endemic to cattle and can cause coinfections, complicating disease dynamics and control. However, the host-related factors influencing these infections under tropical conditions remain poorly understood. This study aimed to investigate the occurrence of hemotropic monoinfections and coinfections in ruminants tested for hemotropic pathogens and to identify host-related factors associated with coinfection in cattle under field conditions in Colombia. A total of 104 animals were included: 91 cattle, 10 buffaloes, and 3 goats. Among the cattle, 34 (37.4%) exhibited monoinfections, 47 (51.6%) had coinfections, and 10 tested negative. In buffaloes, seven (70%) presented monoinfections, and two (20%) presented coinfections; in goats, one had a monoinfection, and one had a coinfection, most frequently involving Mycoplasma spp. The predominant coinfection patterns were Anaplasma&#x2009;+&#x2009;Mycoplasma and Mycoplasma&#x2009;+&#x2009;Trypanosoma, particularly in Bos indicus cattle. Bivariate and multivariable analyses revealed that breed was the strongest predictor of coinfection, with animals of less common breeds showing 93% lower odds (aOR&#x2009;=&#x2009;0.07; 95% CI: 0.02-0.30; p&#x2009;<&#x2009;0.001). Bos taurus individuals also tended toward lower odds of coinfection in the multivariable model, although this trend did not reach statistical significance. Our findings demonstrate a high frequency of hemotropic coinfections in cattle, particularly those involving Mycoplasma spp., and highlight the influence of host-related factors on infection dynamics. These results underscore the importance of integrating demographic and genetic information into surveillance and prevention strategies to improve the management of hemotropic infections in tropical livestock systems.

Animals

Near-Whole-Genome Sequencing of Peste Des Petits Ruminants Virus Lineage IV From the Savannah District, Northern C&#xf4;te d'Ivoire in 2023.

Peste des petits ruminants (PPR) is a highly contagious viral disease affecting sheep and goats, causing substantial economic losses in endemic countries. In the Savannah district of C&#xf4;te d'Ivoire, knowledge of the genetic diversity and molecular epidemiology of the PPR virus (PPRV) remains limited. This study investigated the genetic diversity and phylogenetic relationships of PPRV circulating in this region using whole-genome sequencing (WGS). A cross-sectional survey was conducted between September and December 2023. Nasal swabs collected from sheep and goats were screened for PPRV ribonucleic acid (RNA) using real-time reverse transcription polymerase chain reaction (RT-qPCR). Samples with low quantification cycle (Cq) values of less than 35 and successful multiplex PCR amplification profiles were selected for sequencing using the Oxford Nanopore MinION platform. Near-complete consensus genomes were generated through reference-based assembly and analysed alongside representative strains from all recognised PPRV lineages. Of the 355 samples analysed, 25 (7.0%) tested positive for PPRV RNA, with positive detections in all three surveyed regions (Poro, Tchologo and Bagou&#xe9;). The four samples with the lowest Cq values, originating from all three administrative regions, were successfully sequenced, generating genomes that covered 82.0%-86.2% of the reference genome at a depth of &#x2265; 10 &#xd7;. The missing regions were mainly located at the 5' and 3' genomic termini, as well as in limited internal regions associated with amplicon dropout. Phylogenetic analysis revealed that all four sequences belonged to lineage IV and exhibited high nucleotide similarity (98.1%-99.9%). The Ivorian strains clustered with recent lineage IV viruses from West, North and Central Africa, whereas historical Ivorian lineages I and II formed distinct clades. These findings confirm the predominance of lineage IV in northern C&#xf4;te d'Ivoire and provide baseline genomic data to support molecular epidemiological surveillance in the region.

PPRV

Mapping articular cartilage maturation across postnatal development by proteomics.

OBJECTIVE: Articular cartilage has a specialised extracellular matrix that provides tensile strength and resistance to compression, but repair capacity is limited. Matrix remodelling during growth is essential for long-term tissue function, yet the underlying protein-level adaptations remain poorly characterised in large-animal models relevant to human joint biology. DESIGN: Using non-targeted, label-free mass spectrometry-based proteomics, we profiled full-thickness articular cartilage from goats across seven postnatal ages from neonatal to adult (n = 3 per age). Cartilage proteins were extracted using guanidine-based solubilisation and analysed by mass spectrometry. Selected proteins were further examined by immunohistochemistry. RESULTS: We identified 799 proteins across the seven ages, of which 157 matrisome components grouped into six categories. Development was associated with increased abundance of proteins involved in matrix organisation and stabilisation, including COL6A1, LOX, TIMP3 and CILP. Enrichment analysis revealed a shift from collagen biosynthesis and fibrillogenesis in early postnatal cartilage to elastic fibre organisation, integrin-matrix interactions and glycosaminoglycan metabolism in mature tissue, consistent with transition from matrix assembly to maintenance. Lysozyme increased with age, suggesting a structural role that warrants further study. Several proteins enriched in mature cartilage, including CILP, HTRA1, FN1 and SPP1, have also been implicated in osteoarthritis, suggesting that some molecular features of mature ECM maintenance are shared with diseased tissue. Immunohistochemistry confirmed stable COL2 localisation, loss of deep-zone COL10 staining with maturation and emergence of superficial PRG4 expression in adult cartilage. CONCLUSIONS: Our findings define the proteomic trajectory of cartilage maturation and provide a molecular reference for joint development and matrix ageing.

Animals

Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.

The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, total scaffolds = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identifying key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control.

Animals

Pan-genomics and multi-omics for deciphering genetic variation and accelerating genetic improvement in ruminant livestock.

Livestock reference genomes have transformed the discovery of variants associated with production, reproduction, health, and environmental adaptation. Nevertheless, a single linear reference represents only one mosaic haplotype and incompletely captures sequence diversity within a species, particularly structural variants, copy-number changes, repeat-rich regions, and breed-specific sequences. Pangenomes address this limitation by integrating multiple high-quality assemblies or population-scale variants into a unified sequence or graph representation. Concurrently, multi-omics approaches connect genomic variation with transcriptomic, epigenomic, manuscriptproteomic, metabolomic, and microbiome responses, thereby improving biological interpretation of genotype-phenotype relationships. This review synthesizes recent progress in livestock pangenomics and multi-omics, with emphasis on cattle, goats, sheep, water buffalo, and chickens. It describes advances in long-read and haplotype-resolved sequencing, graph construction, structural-variant discovery and genotyping, functional annotation, and integrative analysis. Recent pangenome studies have uncovered substantial non-reference sequence, reduced reference bias, identified breed- and population-specific structural variants, and resolved candidate variants underlying pigmentation, body size, tail morphology, cashmere production, altitude adaptation, and other economically relevant traits. However, translation into routine breeding remains constrained by uneven population representation, inconsistent structural-variant definitions, limited functional annotation, computational demands, and insufficient validation across environments. Future progress will depend on diverse near-complete assemblies, graph-aware imputation and genomic prediction, long-read transcriptomics, single-cell and spatial omics, rigorous causal validation, and open, interoperable resources. Together, these developments can support more accurate, resilient, and biologically informed livestock improvement. Importantly, current dairy-cattle evidence indicates that pangenome-derived structural variants can substantially improve variant discovery and functional interpretation while yielding only marginal average gains in routine genomic prediction, favoring targeted augmentation rather than wholesale replacement of established SNP-based evaluations.

Animals

Phylogeographic analysis of Staphylococcus nepalensis reveals global occurrence of antimicrobial-resistant lineages carrying the sal(E) resistance gene.

BACKGROUND: Staphylococcus nepalensis is an emerging species first described in 2003 from the respiratory tract of goats in Nepal. We report the identification of S. nepalensis of a hypersaline lagoon in Brazil, along with in-depth phylogeographical and resistome analysis of publicly available genomes. METHODS AND RESULTS: During a local survey from hypersaline aquatic environments in Rio de Janeiro, Brazil, two staphylococcal strains were recovered, designated as COLB and AM1. These isolates were subjected to antimicrobial susceptibility testing, genomic sequencing, and comprehensive phylogenomic analyses. Genomic analysis confirmed the taxonomic identity of COLB and AM1 as S. nepalensis. Both isolates harbored the sal(E) conferring resistance to pleuromutilins and streptogramin A, whereas tet(K) conferring to tetracyclines. Additionally, AM1 carried lnu(A), consistent with the reduced susceptibility to clindamycin (MIC&#x2009;=&#x2009;2&#xa0;&#xb5;g/mL) relative to COLB. Genes associated with arsenic and copper tolerance, and the replicons rep7a and rep19c, were confirmed. Phylogenomic analysis indicated that COLB and AM1 were clonally related (1 cgSNP-difference) but distinct from global isolates. Phylogeographic analysis revealed wide geographic occurrence, with some lineages carrying blaZ and mecA associated with beta-lactamase production and methicillin resistance, respectively. Strikingly, sal(E) is conserved across all S. nepalensis genomes. CONCLUSIONS: The findings confirm the presence of S. nepalensis in South America as early as 2016 and documented among available genomes from environmental, human, and animal-associated sources. Furthermore, reveal the circulation of some lineages carrying clinically relevant antimicrobial genes, underscoring the importance of accurate species identification and continuous genomic surveillance and potential One Health relevance.

Phylogeography

A homogeneous immunoassay based on AlphaLICA technology for detecting florfenicol residues in animal-derived foods.

Florfenicol (FF), a broad-spectrum amide antibiotic widely used in livestock, poultry, and aquaculture, poses potential threats to food safety and public health due to its residual accumulation. In this study, a novel homogeneous immunoassay based on Amplified Luminescent Proximity Homogeneous Assay (AlphaLICA) technology was developed for the first time for rapid screening of FF residues in milk and egg matrices. By covalently immobilizing the FF-BSA conjugate and goat anti-mouse IgG onto luminescent and photosensitive microspheres, respectively, the method achieved wash-free, homogeneous quantitative detection through a competitive immunoreaction. Under optimized conditions, the assay exhibited a linear range of 0.2-16.2 ng mL-1, with a limit of detection of 9.7 pg mL-1 and a limit of quantification of 183 pg mL-1. The intra- and inter-batch coefficients of variation ranged from 3.08% to 5.70% and 2.44% to 7.09%, respectively. Spike recovery rates in milk and egg matrices ranged from 93.18% to 107.17% (RSD &#x2264; 5.57%). Cross-reactivity with 11 other common antibiotics, including chloramphenicol and thiamphenicol, was below 0.1%, demonstrating excellent specificity. Comparative analysis with a commercial ELISA kit showed high consistency (r2 = 0.9332, p < 0.001). With high sensitivity, strong specificity, simple operation, and a detection time of only 10 min, this method provides a reliable technical platform for high-throughput, rapid monitoring of FF residues in milk and egg matrices.

Journal Article

LCORL and STC2 Variants Increase Body Size and Growth Rate in Cattle and Other Animals.

Natural variants can significantly improve growth traits in livestock and serve as safe targets for gene editing, thus being applied in animal molecular design breeding. However, such safe and large-effect mutations are severely lacking. Using ancestral recombination graphs, we investigated recent selection signatures in beef cattle breeds, pinpointing sweep-driving variants in the LCORL and STC2 loci with notable effects on body size and growth rate. The ACT-to-A frameshift mutation in LCORL occurs mainly in central-European cattle, and stimulates growth. Remarkably, convergent truncating mutations were also found in commercial breeds of sheep, goats, pigs, horses, dogs, rabbits, and chickens. In the STC2 gene, we identified a missense mutation (A60P) located within the conserved region across vertebrates. We validated the two natural mutations in gene-edited mouse models, where both variants in homozygous carriers significantly increase the average weight by 11%. Our findings provide insights into a seemingly recurring gene target of body size enhancing truncating mutations across domesticated species, and offer valuable targets for gene editing-based breeding in animals.

Animals

Whole-Genome Sequencing Reveals Co-Infection with Bovine Viral Diarrhea Virus, Bovine Enterovirus, and Caprine Parainfluenza Virus Type 3 in a Calf from a Cattle Herd in Xizang, China.

Although mixed viral infections are increasingly recognized as contributors to bovine diarrhea syndrome, diagnosing such co-infections remains challenging, particularly in high-altitude regions where surveillance is limited. In July 2024, a calf presenting with severe diarrhea and respiratory distress was identified on a cattle farm in Linzhi, Xizang, China. Using unbiased whole-genome sequencing (WGS) of the fecal sample, we assembled near-complete genomes of three distinct RNA viruses: two bovine viral diarrhea virus type 1 (BVDV-1) strains (subtypes 1v and 1q, designated BVDV-1/XZ87 and XZ87), one bovine enterovirus (genotype EV-E, designated BEV/XZ87), and one caprine parainfluenza virus type 3 (CPIV3/XZ87). The CPIV3/XZ87 genome exhibited 99.9% nucleotide identity to the goat-derived GS2017-2 strain from Jiangsu, China, raising the possibility of viral spread through livestock trade. Quantitative real-time PCR (RT-qPCR) confirmed the presence of all three pathogens (Ct values: 24.78 for BEV, 25.98 for CPIV3, and 31.28 for BVDV). This study provides the genomic evidence of a triple co-infection involving BVDV-1, BEV, and CPIV3 in Xizang. It illustrates the potential of WGS for unbiased pathogen detection in complex clinical specimens. The near-complete genomes generated here fill critical gaps in the virological surveillance of this epidemiologically under-sampled high-altitude region.

bovine enterovirus

Epidemiological overview of Cryptosporidium infection in Capra hircus from southern Khyber Pakhtunkhwa, Pakistan.

Objectives: Cryptosporidium is a protozoan parasite that commonly infects livestock, including Capra hircus, causing diarrhea, dehydration, and sometimes mortality. These infections lead to substantial economic losses in the farming industry. This study aimed to determine the prevalence and associated risk factors, such as region, season, age, and sex, of Cryptosporidium infection in C. hircus in southern Khyber Pakhtunkhwa, Pakistan. Materials and Methods: A total of 360 fecal samples were collected from C. hircus from the Kohat, Bannu, and Lakki Marwat Districts of Khyber Pakhtunkhwa, Pakistan. Fecal smears were stained using the modified Ziehl-Neelsen method, and statistical analysis, including chi-square tests, was employed to assess the association between Cryptosporidium infection prevalence and various factors. Results: The overall Cryptosporidium infection prevalence was 20.55% (74/360). District-wise analysis revealed the highest prevalence in Kohat (23.33%), followed by Bannu (20%) and Lakki Marwat (18.33%). Monthly examination identified August as the peak prevalence month (36.67%), displaying non-significant monthly variations (p = 0.075). Seasonal disparity indicated a significantly higher prevalence in the summer (30%) compared to other seasons (p = 0.008). Age-wise prevalence demonstrated susceptibility in kids aged &#x2264; 15 days (&#x2264; 33.93%), with significant overall age-based differences (p = 0.001). Female kids exhibited a slightly higher prevalence at 22.22% compared to males (19.19%), with no significant gender-based difference (p = 0.479). Conclusions: This study highlights the influence of geographic, seasonal, and demographic factors on Cryptosporidium prevalence in goat populations. The findings emphasize the importance of implementing targeted preventive measures. Recommended strategies include farmer education programs, seasonal deworming schedules, early screening for infection, and strict hygiene and water sanitation practices to reduce transmission risks effectively.

Cryptosporidiosis

Sex-specific genetic predictors of Alzheimer's disease biomarkers.

Cerebrospinal fluid (CSF) levels of amyloid-&#x3b2; 42 (A&#x3b2;42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF A&#x3b2;42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In A&#x3b2;42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p&#x2009;=&#x2009;0.04) and rs13115400 near LINC00290 (p&#x2009;=&#x2009;0.002). These loci showed stronger associations among females (&#x3b2;&#x2009;=&#x2009;-&#x2009;0.03, p&#x2009;=&#x2009;4.25&#x2009;&#xd7;&#x2009;10-8; &#x3b2;&#x2009;=&#x2009;0.03, p&#x2009;=&#x2009;3.97&#x2009;&#xd7;&#x2009;10-8) than males (&#x3b2;&#x2009;=&#x2009;-&#xa0;0.02, p&#x2009;=&#x2009;0.009; &#x3b2;&#x2009;=&#x2009;0.01, p&#x2009;=&#x2009;0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values&#x2009;<&#x2009;0.02) but not males (p&#x2009;>&#x2009;0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p&#x2009;=&#x2009;0.004), driven by a stronger association among females (&#x3b2;&#x2009;=&#x2009;0.05, p&#x2009;=&#x2009;4.57&#x2009;&#xd7;&#x2009;10-10) compared to males (&#x3b2;&#x2009;=&#x2009;0.02, p&#x2009;=&#x2009;0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale&#x2009;=&#x2009;0.047; pmale&#x2009;=&#x2009;0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p&#x2009;=&#x2009;0.006; CLDN16 p&#x2009;=&#x2009;0.002) but not males (p&#x2009;&#x2265;&#x2009;0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.

Aged, 80 and over

Animal farming and the oral microbiome in the Agricultural Health Study.

BACKGROUND: Raising farm animals imparts various exposures that may shape the human microbiome. The oral microbiome has been increasingly implicated in disease development. Animal farming has also been associated with certain chronic diseases such as cancer; however, underlying biological mechanisms are unclear. We investigated associations between raising farm animals and the oral microbiome in the Agricultural Health Study. METHODS: This analysis included 1,245 participants (865 farmers and 380 spouses) who provided oral wash specimens and information on types and numbers of specific animals raised on their farms within 2 years before sample collection. The oral microbiome was measured by sequencing the V4 region of the 16S ribosomal RNA gene. We evaluated associations of farm animal exposures with alpha and beta diversity metrics (within- and between-sample diversity, respectively), as well as presence and relative abundance of specific bacterial genera. All analyses adjusted for potential confounders (e.g., age, sex, smoking, alcohol consumption). RESULTS: Overall, 63&#xa0;% of participants raised farm animals, most commonly cattle (46&#xa0;%) and hogs (20&#xa0;%). Those who raised a large number of hogs (&#x2265;2,000 vs. no hogs) had higher alpha diversity. Conversely, raising sheep/goats and raising larger numbers of poultry were associated with lower alpha diversity. Beta diversity was not significantly different between participants with and without any farm animals. Participants raising any farm animals had higher relative abundance of Porphyromonas and lower relative abundances of Prevotella and Ruminococcaceae UCG-014. Several genera were more likely to be absent with specific animal exposures (e.g., Capnocytophaga for cattle and sheep/goats; Corynebacterium, Dialister, Stomatobaculum, and Solobacterium for sheep/goats and poultry). CONCLUSIONS: This was the largest study of farm animal exposures and the human microbiome to date. Findings suggest that raising specific farm animals may influence the oral microbiome, supporting the need to further investigate the potential role of animal farming in disease etiology.

Microbiota

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.

Alzheimer Disease