The European Portuguese Version of the Brief Negative Symptom Scale.

Negative symptoms reflect a currently much-untreated loss of normal functioning and are frequently found in psychotic disorders. We present the first translation of the Brief Negative Symptom Scale (BNSS) to European Portuguese and evaluate its validity in a sample of Portuguese male patients with a psychotic spectrum disorder. The Portuguese BNSS showed excellent internal consistency, high convergent validity (i.e., strong correlation with the PANSS negative factor), and high discriminant validity (i.e., a lack of association with the PANSS positive factor). In sum, the present European Portuguese BNSS has shown to be reliable, thus extending this instrument's clinical availability worldwide.

Preantral follicle numbers and size in heifers carrying Trio, a bovine high fecundity allele.

In brief: The bovine high fecundity allele, Trio, results in the occurrence of multiple ovulations and is characterized by antral follicles that develop slower and acquire ovulatory capacity at smaller sizes. This study provides novel information on the effect of the Trio allele on early folliculogenesis. Abstract: The bovine high fecundity allele, Trio, causes overexpression in granulosa cells (GCs) of SMAD6, an inhibitor of BMP15-activated SMAD signalling. Furthermore, the Trio allele results in antral follicles that develop slower, acquire ovulatory capacity at smaller sizes, and have three-fold greater ovulation rate compared to half-sib non-carriers. The present study was designed to determine preantral follicle numbers and size in Trio carrier and non-carrier cattle testing the hypothesis that inhibition of SMAD signalling would alter preantral follicle activation and/or growth. Ovarian tissues from Trio carrier (n = 12) and non-carrier (n = 12) heifers were obtained by laparotomy after follicle wave synchronization. Follicle numbers and dimensions were determined for each stage of development (primordial, transitional, primary, and secondary) from paraffin-embedded sections. There were no differences in the number of primordial, transitional, or secondary follicles or in antral follicle count, circulating AMH, or ovarian volume between carriers and non-carriers. Trio carriers had ~2.5-fold greater (P < 0.01) number of primary follicles than non-carriers, and transitional and primary follicles were larger (~1.2-fold; P < 0.1) in Trio carriers. Oocyte volume of primordial and transitional follicles was not different between genotypes; however, oocytes were larger (P < 0.05) in primary (~1.3-fold) and secondary (~1.8-fold) follicles for Trio carriers. Granulosa cell numbers were not different (P > 0.3) between carriers and non-carriers, irrespective of the stage of development. These results suggest that, after primordial follicle activation, follicles in Trio carrier cattle have slower progression through the primary stage, hence the larger oocyte and greater number of primary follicles.

SMAD6 inhibits granulosa cell proliferation and follicle growth rate in carrier and noncarrier heifers of the Trio allele.

In brief: Follicle selection is a key event in monovular species. In this manuscript, we demonstrate the role of SMAD6 in promoting decreased granulosa cell proliferation and follicle growth rate in carriers vs noncarriers of the Trio allele and after vs before follicle deviation. Abstract: Cattle are generally considered a monovular species; however, recently, a bovine high fecundity allele, termed the Trio allele, was discovered. Carriers of Trio have an elevated ovulation rate (3-5), while half-sibling noncarriers are monovular. Carriers of the Trio allele have overexpression in granulosa cells of SMAD6, an inhibitor of oocyte-derived regulators of granulosa cell proliferation and differentiation. In experiment 1, follicle size was tracked for each follicle during a follicular wave. Follicle growth rate was greater before vs after follicle deviation in both carriers and noncarriers. Additionally, follicle growth rate was consistently less in carriers vs noncarriers. In experiment 2, we collected granulosa cells from follicles before and after deviation for evaluation of granulosa cell gene expression. Granulosa cell proliferation was less in carriers vs noncarriers and after vs before follicle deviation (decreased expression of cell cycle genes CCNB1 and CCNA2). The decreased granulosa cell proliferation in noncarriers after deviation was associated with increased SMAD6 expression. Similarly, in experiment 3, decreased expression of SMAD6 in granulosa cells of noncarriers cultured in vitro for 60 h was associated with increased expression of cell cycle genes. This suggests that SMAD6 may not just be inhibiting follicle growth rate in carriers of Trio but may also play a role in the decreased follicle growth after deviation in noncarriers. The hypotheses were supported that (1) follicle growth and granulosa cell proliferation decrease after deviation in both carriers and noncarriers and that (2) granulosa cell proliferation is reduced in carriers compared to noncarriers.

Negative symptoms in the clinic: we treat what we can describe.

Recent research has led to important changes in the concepts and assessment of negative symptoms in schizophrenia. We review current negative symptom concepts and their clinical implications, as well as new methods of assessing these symptoms. These changes hold promise for improving our understanding and treatment of negative symptoms.

A new era for the negative symptoms of schizophrenia.

Negative symptoms remain one of the major unmet needs for people with schizophrenia, and the past decade has witnessed a surge in interest in negative symptoms. In this themed issue, we present new concepts of negative symptoms and recent findings on their epidemiology and pathophysiology and on therapeutic options for their management.

Longitudinal effect of clozapine-associated sedation on motivation in schizophrenia: naturalistic longitudinal study.

Negative symptoms of schizophrenia manifest as reduced motivation and pleasure (MAP) and impaired emotional expressivity (EXP). These can occur as primary phenomena, but have also been suggested to occur secondary to other clinical factors, including antipsychotic-induced sedation. However, this relationship has not been established formally. Here, we examined the effect of antipsychotic-induced sedation (assessed via the proxy of total daily sleep duration) on MAP and EXP in a cohort of 187 clozapine-treated patients with schizophrenia followed for over 2 years on average, using multilevel regression and mediation models. MAP, but not EXP, was adversely influenced by sedation, independently of the severity of psychosis or depression. Moreover, clozapine impaired MAP indirectly by worsening sedation, but after accounting for clozapine-induced sedation, clozapine improved MAP. Our results highlight the importance of addressing sedative side-effects of antipsychotics to improve clinical outcomes.

Degree of leukochimerism with calf age in Angus-crossbred twin sets.

Twinning in cattle is infrequent and usually undesired. It can result in an increased occurrence of abortion and dystocia, reduced calf survival and a high likelihood of freemartinism in mixed-sex twins. Twin gestations are also commonly associated with the formation of placental vascular anastomoses (PVA) between twins. Through PVA they share blood, hormones (leading to freemartinism in mixed sex twins) and hematopoietic stem cells, which are the progenitors of white blood cells. The sharing of stem cells between twins can result in leukochimeric twin sets. These are twins that have white blood cells derived from both self and the co-twin owing to the fetal migration of hematopoietic stem cells from the extraembryonic mesoderm of the yolk sac to final sites like bone marrow and thymus. This study examined the degree to which this leukochimerism changes with age. DNA was extracted from hair bulbs containing mesenchymal dermal papilla to determine the individual's true genotype and blood samples were obtained at six time points from 1 week to 8 months of age to assess leukochimerism. Samples were genotyped using a medium density SNP chip, and quantitative estimates of allele frequency were determined using SNPs for which members of a twin set had alternative homozygous genotypes. The results indicate statistically significant changes in the proportion of self and co-twin with age and suggest that by 2-4 months of age the genotypic mix in white blood cells represents the hematopoetic stem cell population resident in the individual (i.e. permanently found in thymus and bone marrow).

Identifying genetic variants and pathways influencing daughter averages for twinning in North American Holstein cattle and evaluating the potential for genomic selection.

Multiple birth in dairy cattle is a detrimental trait both economically for producers and for animal health. Genetics of twinning is complex and has led to several quantitative trait loci regions being associated with increased twinning. To identify variants associated with this trait, calving records from 2 time periods were used to estimate daughter averages for twinning for Holstein bulls. Multiple analyses were conducted and compared including GWAS, genomic prediction, and gene set enrichment analysis for pathway detection. Although pathway analysis did not yield many congruent pathways of interest between data sets, it did indicate two of interest. Both pathways have ties to the strong candidate region on BTA11 from the genome-wide association analysis across data sets. This region does not overlap with previously identified quantitative trait loci regions for twinning or ovulation rate in cattle. The strongest associated SNPs were upstream from 2 candidate genes LHCGR and FSHR, which are involved in folliculogenesis. Genomic prediction showed a moderate correlation accuracy (0.43) when predicting genomic breeding values for bulls with estimates from calving records from 2010 to 2016. Future analysis of the region on BTA11 and the relation of the candidate genes could improve this accuracy.

Selection of fewer dominant follicles in Trio carriers given GnRH antagonist and luteinizing hormone action replaced by nonpulsatile human chorionic gonadotropin†.

Studying selection of multiple dominant follicles (DFs) in monovulatory species can advance our understanding of mechanisms regulating selection of single or multiple DFs. Carriers of the bovine high fecundity Trio allele select multiple DFs, whereas half-sib noncarriers select a single DF. This study compared follicle selection during endogenous gonadotropin pulses versus during ablation of pulses with Acyline (GnRH antagonist) and luteinizing hormone (LH) action replaced with nonpulsatile human chorionic gonadotropin (hCG) treatment in Trio carriers (n = 28) versus noncarriers (n = 32). On Day 1.5 (Day 0 = ovulation), heifers were randomized: (1) Control, untreated; (2) Acyline, two i.m. doses (Days 1.5 and D3) of 3 µg/kg; (3) hCG, single i.m. dose of 50 IU hCG on Day 1.5 followed by daily doses of 100 IU; and (4) Acyline + hCG. Treatments with nonpulsatile hCG were designed to replace LH action in heifers treated with Acyline. Acyline treatment resulted in cessation of follicle growth on Day 3 with smaller (P < 0.0001) maximum follicle diameter in Trio carriers (6.6 ± 0.2 mm) than noncarriers (8.7 ± 0.4 mm). Replacement of LH action (hCG) reestablished follicle diameter deviation and maximum diameter of DFs in both genotypes (8.9 ± 0.3 mm and 13.1 ± 0.5 mm; P < 0.0001). Circulating follicle stimulating hormone (FSH) was greater in Acyline-treated than in controls. Finally, Acyline + hCG decreased (P < 0.0001) the number of DFs from 2.7 ± 0.2 to 1.3 ± 0.2 in Trio carriers, with most heifers having only one DF. This demonstrates the necessity for LH in acquisition of dominance in Trio carriers (~6.5 mm) and noncarriers (~8.5 mm) and provides evidence for a role of GnRH-induced FSH/LH pulses in selection of multiple DFs in Trio carriers and possibly other physiologic situations with increased ovulation rate.

The influence of negative and affective symptoms on anhedonia self-report in schizophrenia.

BACKGROUND: Anhedonia, a symptom prevalent in schizophrenia patients, is thought to arise either within negative symptomatology or from secondary sources, such as depression. The common co-occurrence of these diseases complicates the assessment of anhedonia in schizophrenia. METHOD: In a sample of 40 outpatients with chronic schizophrenia, we explored both the validity of the Snaith-Hamilton Pleasure Scale (SHAPS) self-report for anhedonia assessment and those factors influenced its scoring. We assessed negative symptoms using the Brief Negative Symptom Scale (BNSS), depression symptoms using the Calgary Depression Scale for Schizophrenia (CDSS) and cognitive impairment using the Brief Assessment of Cognition in Schizophrenia (BACS), before exploring associations between these scales. RESULTS: The SHAPS was validated for use in schizophrenia. SHAPS scores were not associated with negative symptoms or cognitive impairment, but were linked to a single Depression symptom: Hopelessness (r = 0.52, p < 0.001). CONCLUSIONS: SHAPS scores, therefore, appear to only reflect anticipatory anhedonia arising from the affective domain. We advocate the development of multi-faceted self-report measures to more holistically assess anhedonia in schizophrenia.

Genomic analysis of bovine respiratory disease and lung consolidation in preweaned Holstein calves using clinical scoring and lung ultrasound.

Bovine respiratory disease (BRD) is a leading cause of morbidity and mortality in dairy calves, with detrimental long-term effects that include stunted growth, increased age at first calving, and decreased milk production in first lactation. The objectives of this study were to establish a protocol for objective and efficient assessment of BRD phenotypes in preweaned dairy calves, develop a genomic reference population with well-defined clinical and subclinical phenotypes, identify chromosomal regions associated with BRD in a genome-wide association study, estimate genetic parameters of BRD, and predict genomic breeding values of dairy calves. A total of 1,107 Holstein calves from 6 dairy farms in southern Wisconsin were examined using clinical respiratory scoring and lung ultrasound at 3 and 6 wk of age. The clinical respiratory score was based on visual appraisal of eyes, nose, ears, cough, and temperature. Lung ultrasound scores were assigned based on the amount of consolidation present. Calves were genotyped with a commercially available SNP array and after quality control and imputation to higher density, 690,291 SNP markers and 1,014 individuals remained. Single-step genome-wide association study and single-step genomic best linear unbiased prediction were applied to binary 3- and 6-wk phenotypes considered as overall respiratory healthy versus affected (RESP3, RESP6) or as presence or absence of lung consolidation (CON3, CON6). Lung ultrasound combined with a clinical scoring system allowed for efficient and objective assessment for the prevalence of BRD. Proportions of variance attributed to 1-Mb non-overlapping windows suggested genomic regions that may contain putative candidate genes, most notably regions on Bos taurus autosomes 1, 6, 7, 10, 11, 12, 15, 17, 18, 27, and 28 that explained 0.70 to 1.45% of the genetic variance. Heritability estimates were higher at 3 wk (0.214 and 0.241 for CON3 and RESP3, respectively) than 6 wk (0.084 and 0.111 for CON6 and RESP6, respectively), and mean reliabilities of genomic estimated breeding vales for calves with genotypes and phenotypes ranged from 0.12 for CON6 to 0.30 for RESP3.

Functional dysconnectivity of the limbic loop of frontostriatal circuits in first-episode, treatment-naive schizophrenia.

Frontostriatal circuits dysfunction has been implicated in the etiology and psychopathology of patients with schizophrenia (SZ). However, few studies have investigated SZ-related functional connectivity (FC) alterations in discrete frontostriatal circuits and their relationship with pathopsychology in first-episode schizophrenia (FESZ). The goal of this study was to identify dysfunctions in discrete frontostriatal circuits that are associated with key features of FESZ. To this end, a case-control, cross-sectional study was conducted, wherein resting-state (RS) functional magnetic resonance (fMRI) data were collected from 37 treatment-naïve FESZ patients and 29 healthy control (HC) subjects. Seed-based FC analyses were performed by placing six bilateral pairs of seeds within a priori defined subdivisions of the striatum. We observed significantly decreased FC for the FESZ group relative to the HC group [p < .05, family-wise error (FWE)-corrected] in the limbic loop, but not in the sensorimotor or associative loops, of frontostriatal circuitry. Moreover, bilaterally decreased inferior ventral striatum/nucleus accumbens (VSi)-dorsal anterior cingulate cortex (dACC) FC within the limbic loop correlated inversely with overall FESZ symptom severity and the disorganization factor score of PANSS. These findings provide new insight into the role of frontostriatal limbic loop hypoconnectivity in early-stage schizophrenia pathology and suggest potential novel therapeutic targets.

Trio a novel bovine high-fecundity allele: II. Hormonal profile and follicular dynamics underlying the high ovulation rate.

The newly discovered Trio high-fecundity allele produces multiple ovulations in cattle. This study evaluated (1) size and growth rates of follicles in Trio carriers during a synchronized follicular wave, induced by follicle aspiration; (2) follicle-stimulating hormone (FSH) patterns associated with the follicular wave; (3) size of corpora lutea (CL) and circulating progesterone; and (4) intrafollicular estradiol concentrations prior to normal deviation. Trio carriers had mean dominant follicles that were significantly smaller in diameter and volume than noncarriers. Onset of diameter deviation occurred at ∼3 days after the last follicle aspiration in both genotypes despite Trio carriers having much smaller individual follicles. Follicles of Trio carriers grew at a slower rate than noncarrier follicles (∼65% in mm/day or ∼30% in mm3/day) resulting in much smaller individual dominant follicles (∼25% volume). However, total dominant follicle volume, calculated as the sum of all dominant follicles in each animal, was similar in carriers and noncarriers of Trio throughout the entire follicular wave. Circulating FSH was greater in Trio carriers during the 24 h encompassing deviation. Trio carriers had significantly more ovulations than noncarriers, and individual CL volume was smaller, although total luteal tissue volume and circulating P4 were not different. Thus, increased ovulation rate in Trio carriers relates to smaller individual follicles (one-third the volume) near the time of deviation due to slower follicle growth rate, although time of deviation is similar, with increased circulating FSH near deviation leading to selection of multiple dominant follicles in Trio carriers with similar total follicle volume.

Trio, a novel high fecundity allele: I. Transcriptome analysis of granulosa cells from carriers and noncarriers of a major gene for bovine ovulation rate.

A major gene for bovine ovulation rate has been mapped to a 1.2 Mb region of chromosome 10. Screening of coding regions of positional candidate genes within this region failed to reveal a causative polymorphism, leading to the hypothesis that the phenotype results from differences in candidate gene expression rather than alteration of gene structure. This study tested differences in expression of positional candidate genes in granulosa cells between carriers and noncarriers of the high fecundity allele, as well as characterizing differences in the transcriptomic profile between genotypes. Five carriers and five noncarriers, female descendants of "Trio," a carrier of the high fecundity allele were initially used in an RNA-seq analysis of gene expression. Four of ten samples were contaminated with theca cells, so that six samples were used in the final analysis (three of each genotype). Of 14 973 genes expressed, 143 were differentially expressed (false discovery rate P < 0.05) in carriers versus noncarriers. Among the positional candidate genes, SMAD6 was 6.6-fold overexpressed in the carriers compared to noncarriers (P < 5 × 10-5). This result was replicated in an independent group of 12 females (7 carriers and 5 noncarriers) using quantitative real-time PCR; SMAD6 was 9.3-fold overexpressed in carriers versus noncarriers (P = 1.17 × 10-6). Association of overexpression of SMAD6, an inhibitor of the BMP/SMAD signaling pathway, with high ovulation rate corresponds well with disabling mutations in ligands (BMP15 and GDF9) and a receptor (BMPR1B) of this pathway that cause increased ovulation rate in sheep.

Trio, a novel bovine high fecundity allele: III. Acquisition of dominance and ovulatory capacity at a smaller follicle size.

The acquisition of dominance and ovulatory capacity was evaluated in follicles from cows that were carriers or half-sibling noncarriers of the Trio allele. Follicle size at acquisition of follicular dominance was determined by evaluating whether follicles ovulate after GnRH challenge (ovulatory capacity-experiment 1) and by determination of intrafollicular concentrations of estradiol and free insulin like growth factor 1 (IGF1) and relative mRNA expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), luteinizing hormone/choriogonadotropin receptor (LHCGR), and pappalysin 1 (PAPPA, previously known as pregnancy-associated plasma protein A, pappalysin 1) in granulosa cells from follicles of different sizes (experiment 2). Ovulatory capacity developed in follicles at 8.3 mm (50% ovulatory capacity) in noncarriers but at smaller sizes (5.5 mm) in Trio carriers. Similarly, in experiment 2, follicles of Trio carriers acquired a dominant phenotype, as determined by intrafollicular estradiol and CYP19A1, LHCGR, and PAPPA mRNA expression in granulosa cells, at significantly smaller sizes but at a similar time after wave emergence. Overall, dominance/ovulatory capacity was acquired when follicles of Trio carriers were ∼30% the size (volume basis) of follicles in noncarriers. In addition, follicles in Trio carriers appear to acquire dominance in a hierarchal manner, as demonstrated by the progressively greater number of follicles with a dominant phenotype between days 2 and 4 after wave emergence. Thus, results from this study provide further support for a physiological model in which selection of multiple follicles in Trio allele carriers is characterized by acquisition of dominance at a smaller follicle size but at a similar time in the follicular wave with multiple follicles acquiring dominance in a hierarchal sequence.

Proteomic analysis of follicular fluid in carriers and non-carriers of the Trio allele for high ovulation rate in cattle.

This study was conducted to characterise differences in follicular fluid proteins between carriers and non-carriers of a bovine allele for high ovulation rate. A total of four non-carrier and five carrier females were used in an initial study with four and six additional non-carriers and carriers respectively used in a validation study. Emergence of the follicular wave was synchronised and the ovaries containing the dominant follicle(s) were extracted by ovariectomy for follicular fluid collection. A hexapeptide ligand library was used to overcome the masking effect of high-abundance proteins and to increase detection of low-abundance proteins in tandem mass spectrometry. After correcting for multiple comparisons, only two proteins, glia-derived nexin precursor (SERPINE2) and inhibin ß B chain precursor (INHBB), were significantly differentially expressed (false-discovery rate <0.05). In a replicate study of analogous design differential expression was confirmed (P<0.05). Joint analysis of results from the two studies indicated that three additional proteins were consistently differentially expressed between genotypes. For three of these five, previous studies have indicated that expression is increased by transforming growth factor-ß-bone morphogenetic protein signalling; their reduction in follicular fluid from carrier animals is consistent with the ~9-fold overexpression of SMAD family member 6 (SMAD6) in carriers that is inhibitory to this pathway.

Short communication: Heritability of susceptibility to infection by Mycobacterium avium ssp. paratuberculosis in Holstein cattle.

Johne's disease in cattle is the result of infection of the small intestine by Mycobacterium avium ssp. paratuberculosis (MAP), leading to an incurable inflammatory bowel disease (Johne's disease or paratuberculosis). The disease is a concern both for its direct cost to dairy producers and for its zoonotic potential. The objective of this study was to estimate the heritability for susceptibility to infection of cattle by MAP using Johne's testing records (ELISA test for presence of antibodies to MAP in milk or blood) from US Holstein cattle from 2009 to 2016. Data sets were edited to include records from herds with 100 or more total records and sires with 50 or more daughters. Data sets were further edited to include (1) only herds with at least 1 positive test, (2) herds with at least 2.5% positive test results, and (3) herds with at least 5% positive test results to examine the effect of data from herds with higher proportions of positive tests, and presumably higher pathogen exposure, on heritability estimates. Two models were used in this study, a linear sire model and a binary threshold-probit sire model. Both were mixed models considering fixed effects of herd and age at test, the latter as a covariate accounting for linear and quadratic effects; random effects included sire and residual. Analyses were conducted using a restricted maximum likelihood method. Heritability estimates (±standard error) from the linear model were 0.041 ± 0.004, 0.050 ± 0.004, and 0.062 ± 0.007 for data from herds with at least 1 positive test, ≥2.5% positive tests, and ≥5% positive tests, respectively. Heritability estimates from the threshold model were 0.157 ± 0.014, 0.174 ± 0.016, and 0.186 ± 0.021 for data from herds with at least 1 positive test, ≥2.5% positive tests, and ≥5% positive tests, respectively. Heritability estimates from the linear model were affected by population incidence for positive tests, in contrast to estimates from the threshold model, likely accounting for the difference in magnitude of heritability estimates between models and suggesting that the threshold model analysis is the better choice. Heritability estimates increased as data were restricted to herds with presumed higher MAP exposure for both linear model and threshold model analyses. These estimates are similar to previous estimates in other dairy cattle populations and suggest the potential for selection to lessen susceptibility to MAP infection.

Short communication: Heritability of twinning rate in Holstein cattle.

Multiple births or twinning in cattle is a naturally occurring reproductive phenomenon. For dairy cattle, twinning is considered a detrimental trait as it can be harmful to cow and calf as well as costly to the producer. The objective of this study was to examine recent US calving records for the Holstein breed to determine a current estimate of heritability for twinning rate along with effects of season and parity. Two models were used in this study: a linear sire model and a binary threshold-logit sire model. Both were mixed models considering fixed effects and random effects. Analyses were conducted using a restricted maximum likelihood method. Heritability estimates were 0.0192 ± 0.0009 and 0.1420 ± 0.0069 for the linear and threshold models, respectively. Repeatabilities from the linear and threshold-logit models were 0.0443 ± 0.0012 and 0.2310 ± 0.0072, respectively. The nonzero estimates of heritability indicate the potential to select against this trait for genetic improvement of Holstein cattle.

An across-breed genome wide association analysis of susceptibility to paratuberculosis in dairy cattle.

Paratuberculosis is a chronic disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). It occurs worldwide and causes a significant loss in the animal production industry. There is no cure for MAP infection and vaccination is problematic. Identification of genetics of susceptibility could be a useful adjunct for programs that focus on management, testing and culling of diseased animals. A case-control, genome-wide association study (GWAS) was conducted using Holstein and Jersey cattle in a combined analysis in order to identify markers and chromosomal regions associated with susceptibility to MAP infection across-breed. A mixed-model method (GRAMMAR-GC) implemented in the GenABEL R package and a Bayes C analysis implemented in GenSel software were used as alternative approaches to conduct GWAS analysis focused on single SNPs and chromosomal segments, respectively. After conducting quality control, 22 406 SNPs from 2157 individuals were available for the GRAMMAR-GC (Bayes C) analysis and 45 640 SNPs from 2199 individuals were available for the Bayes C analysis. One SNP located on BTA27 (8·6 Mb) was identified as moderately associated (P < 5 × 10-5, FDR = 0·44) in the GRAMMAR-GC analysis of the combined breed data. Nine 1 Mb windows located on BTA 2, 3 (3 windows), 6, 8, 25, 27 and 29 each explained ≥1% of the total proportion of genetic variance in the Bayes C analysis. In an analysis ignoring differences in linkage phase, two moderately significantly associated SNPs were identified; ARS-BFGL-NGS-19381 on BTA23 (32 Mb) and Hapmap40994-BTA-46361 on BTA19 (61 Mb). New common genomic regions and candidate genes have been identified from the across-breed analysis that might be involved in the immune response and susceptibility to MAP infection.