An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance.

Genetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer a complementary control strategy. Hypothesising underlying non-additive genetic variation, we present an approach using genome-wide high density markers to identify genomic loci with dominance effects on bTB resistance and to test previously published regions with heterozygote advantage in bTB. Our data comprised 1151 Holstein-Friesian cows from Northern Ireland, confirmed bTB cases and controls, genotyped with the 700K Illumina BeadChip. Genome-wide markers were tested for associations between heterozygosity and bTB status using marker-based relationships. Results were tested for robustness against genetic structure, and the genotypic frequencies of a significant locus were tested for departures from Hardy-Weinberg equilibrium. Genomic regions identified in our study and in previous publications were tested for dominance effects. Genotypic effects were estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was significant at the chromosome-wide level, explaining 1.7% of the phenotypic variance. In the controls, there were fewer heterozygotes for rs43032684 (P < 0.01) with the genotypic values suggesting that heterozygosity confers a heterozygote disadvantage. The region surrounding rs43032684 had a significant dominance effect (P < 0.01). SNP rs43032684 resides within a pseudogene with a parental gene involved in macrophage response to infection and within a copy-number-variation region previously associated with nematode resistance. No dominance effect was found for the region on chromosome 11, as indicated by a previous candidate region bTB study. These findings require further validation with large-scale data.

Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows.

BACKGROUND: Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics. However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host response to infection could represent a continuum since time of exposure or distinct outcomes due to differing pathogen handling. The relationships between host genetics and variation in host response and pathological sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231 SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls SICCT-negative on multiple occasions. RESULTS: Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes 17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs) variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs) nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance consists of variants of small to moderate effect situated across many chromosomes of the bovine genome. CONCLUSIONS: These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically determined and indicative of different host responses or pathogen handling. There may be at least three distinct outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no detectable pathology.

Genetic evaluation for bovine tuberculosis resistance in dairy cattle.

Genetic evaluations for resistance to bovine tuberculosis (bTB) were calculated based on British national data including individual animal tuberculin skin test results, postmortem examination (presence of bTB lesions and bacteriological culture for Mycobacterium bovis), animal movement and location information, production history, and pedigree records. Holstein cows with identified sires in herds with bTB breakdowns (new herd incidents) occurring between the years 2000 and 2014 were considered. In the first instance, cows with a positive reaction to the skin test and a positive postmortem examination were defined as infected. Values of 0 and 1 were assigned to healthy and infected animal records, respectively. Data were analyzed with mixed models. Linear and logit function heritability estimates were 0.092 and 0.172, respectively. In subsequent analyses, breakdowns were split into 2-mo intervals to better model time of exposure and infection in the contemporary group. Intervals with at least one infected individual were retained and multiple intervals within the same breakdown were included. Healthy animal records were assigned values of 0, and infected records a value of 1 in the interval of infection and values reflecting a diminishing probability of infection in the preceding intervals. Heritability and repeatability estimates were 0.115 and 0.699, respectively. Reliabilities and across time stability of the genetic evaluation were improved with the interval model. Subsequently, 2 more definitions of "infected" were analyzed with the interval model: (1) all positive skin test reactors regardless of postmortem examination, and (2) all positive skin test reactors plus nonreactors with positive postmortem examination. Estimated heritability was 0.085 and 0.089, respectively; corresponding repeatability estimates were 0.701 and 0.697. Genetic evaluation reliabilities and across time stability did not change. Correlations of genetic evaluations for bTB with other traits in the current breeding goal were mostly not different from zero. Correlation with the UK Profitable Lifetime Index was moderate, significant, and favorable. Results demonstrated the feasibility of a national genetic evaluation for bTB resistance. Selection for enhanced resistance will have a positive effect on profitability and no antagonistic effects on current breeding goal traits. Official genetic evaluations are now based on the interval model and the last bTB trait definition.

Modelling gastrointestinal parasitism infection in a sheep flock over two reproductive seasons: in silico exploration and sensitivity analysis.

In reproducing ewes, a periparturient breakdown of immunity is often observed to result in increased fecal egg excretion, making them the main source of infection for their immunologically naive lambs. In this study, we expanded a simulation model previously developed for growing lambs to explore the impact of the genotype (performance and resistance traits) and host nutrition on the performance and parasitism of both growing lambs and reproducing ewes naturally infected with Teladorsagia circumcincta. Our model accounted for nutrient-demanding phases, such as gestation and lactation, and included a supplementary module to manage the age structure of the ewe flock. The model was validated by comparison with published data. Because model parameters were unknown or poorly estimated, detailed sensitivity analysis of the model was performed for the sheep mortality and the level of infection, following a preliminary screening step. The parameters with the greatest effect on parasite-related outputs were those driving animal growth and milk yield. Our model enables different parasite-control strategies (host nutrition, breeding for resistance and anthelmintic treatments) to be assessed on the long term in a sheep flock. To optimize in silico exploration, the parameters highlighted by the sensitivity analysis should be refined with real data.

Mapping and validation of a major QTL affecting resistance to pancreas disease (salmonid alphavirus) in Atlantic salmon (Salmo salar).

Pancreas disease (PD), caused by a salmonid alphavirus (SAV), has a large negative economic and animal welfare impact on Atlantic salmon aquaculture. Evidence for genetic variation in host resistance to this disease has been reported, suggesting that selective breeding may potentially form an important component of disease control. The aim of this study was to explore the genetic architecture of resistance to PD, using survival data collected from two unrelated populations of Atlantic salmon; one challenged with SAV as fry in freshwater (POP 1) and one challenged with SAV as post-smolts in sea water (POP 2). Analyses of the binary survival data revealed a moderate-to-high heritability for host resistance to PD in both populations (fry POP 1 h(2)~0.5; post-smolt POP 2 h(2)~0.4). Subsets of both populations were genotyped for single nucleotide polymorphism markers, and six putative resistance quantitative trait loci (QTL) were identified. One of these QTL was mapped to the same location on chromosome 3 in both populations, reaching chromosome-wide significance in both the sire- and dam-based analyses in POP 1, and genome-wide significance in a combined analysis in POP 2. This independently verified QTL explains a significant proportion of host genetic variation in resistance to PD in both populations, suggesting a common underlying mechanism for genetic resistance across lifecycle stages. Markers associated with this QTL are being incorporated into selective breeding programs to improve PD resistance.

Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis.

Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10(-7)) and myosin IIIB (MYO3B; P=5.4 × 10(-6)). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.

Clinical decision-making augmented by simulation training: neural correlates demonstrated by functional imaging: a pilot study.

BACKGROUND: Investigation of the neuroanatomical basis of clinical decision-making, and whether this differs when students are trained via online training or simulation training, could provide valuable insight into the means by which simulation training might be beneficial. METHODS: The aim of this pilot prospective parallel group cohort study was to investigate the neural correlates of clinical decision-making, and to determine if simulation as opposed to online training influences these neural correlates. Twelve third-year medical students were randomized into two groups and received simulation-based or online-based training on anaphylaxis. This was followed by functional magnetic resonance imaging scanning to detect brain activation patterns while answering multiple choice questions (MCQs) related to anaphylaxis, and unrelated non-clinical (control) questions. Performance in the MCQs, salivary cortisol levels, heart rate, and arterial pressure were also measured. RESULTS: Comparing neural responses to clinical and non-clinical questions (in all participants), significant areas of activation were seen in the ventral anterior cingulate cortex and medial prefrontal cortex. These areas were activated in the online group when answering action-based questions related to their training, but not in the simulation group. The simulation group tended to react more quickly and accurately to clinical MCQs than the online group, but statistical significance was not reached. CONCLUSIONS: The activation areas seen could indicate increased stress when answering clinical questions compared with general non-clinical questions, and in the online group when answering action-based clinical questions. These findings suggest simulation training attenuates neural responses related to stress when making clinical decisions.

Evaluation of the Sherlock 3CG Tip Confirmation System on peripherally inserted central catheter malposition rates.

Peripherally inserted central catheters are often positioned blindly in the central circulation, and this may result in high malposition rates, especially in critically ill patients. Recently, a new technology has been introduced (Sherlock 3CG Tip Positioning System) that uses an electro-magnetic system to guide positioning in the superior vena cava, and then intra-cavity ECG to guide positioning at the cavo-atrial junction. In this observational study, we investigated how the Sherlock 3CG Tip Positioning System would affect peripherally inserted central catheter malposition rates, defined using a post-insertion chest radiograph, in critically ill patients. A total of 239 catheters positioned using the Sherlock 3CG Tip Positioning System were analysed. When an adequate position was defined as low superior vena cava or cavo-atrial junction, 134 catheters (56.1%; 95% CI 50-62%) were malpositioned. When an adequate position was defined as mid/low superior vena cava, cavo-atrial junction or high right atrium (≤ 2 cm from cavo-atrial junction), 49 (20.5%; 95% CI 16-26%) catheters were malpositioned. These malposition rates are significantly lower than our own historical data, which used a 'blind' anthropometric technique to guide peripherally inserted central catheter insertion.

A joint analysis to identify loci underlying variation in nematode resistance in three European sheep populations.

Gastrointestinal nematode infections are one of the main health/economic issues in sheep industries, worldwide. Indicator traits for resistance such as faecal egg count (FEC) are commonly used in genomic studies; however, published results are inconsistent among breeds. Meta (or joint)-analysis is a tool for aggregating information from multiple independent studies. The aim of this study was to identify loci underlying variation in FEC, as an indicator of nematode resistance, in a joint analysis using data from three populations (Scottish Blackface, Sarda × Lacaune and Martinik Black-Belly × Romane), genotyped with the ovine 50k SNP chip. The trait analysed was the average animal effect for Strongyles and Nematodirus FEC data. Analyses were performed with regional heritability mapping (RHM), fitting polygenic effects with either the whole genomic relationship matrix or matrices excluding the chromosome being interrogated. Across-population genomic covariances were set to zero. After quality control, 4123 animals and 38 991 SNPs were available for the analysis. RHM identified genome-wide significant regions on OAR4, 12, 14, 19 and 20, with the latter being the most significant. The OAR20 region is close to the major histocompatibility complex, which has often been proposed as a functional candidate for nematode resistance. This region was significant only in the Sarda × Lacaune population. Several other regions, on OAR1, 3, 4, 5, 7, 12, 19, 20 and 24, were significant at the suggestive level.

Genome-wide association and regional heritability mapping to identify loci underlying variation in nematode resistance and body weight in Scottish Blackface lambs.

The genetic architecture underlying nematode resistance and body weight in Blackface lambs was evaluated comparing genome-wide association (GWA) and regional heritability mapping (RHM) approaches. The traits analysed were faecal egg count (FEC) and immunoglobulin A activity against third-stage larvae from Teladorsagia circumcincta, as indicators of nematode resistance, and body weight in a population of 752 Scottish Blackface lambs, genotyped with the 50k single-nucleotide polymorphism (SNP) chip. FEC for both Nematodirus and Strongyles nematodes (excluding Nematodirus), as well as body weight were collected at approximately 16, 20 and 24 weeks of age. In addition, a weighted average animal effect was estimated for both FEC and body weight traits. After quality control, 44 388 SNPs were available for the GWA analysis and 42 841 for the RHM, which utilises only mapped SNPs. The same fixed effects were used in both analyses: sex, year, management group, litter size and age of dam, with day of birth as covariate. Some genomic regions of interest for both nematode resistance and body weight traits were identified, using both GWA and RHM approaches. For both methods, strong evidence for association was found on chromosome 14 for Nematodirus average animal effect, chromosome 6 for Strongyles FEC at 16 weeks and chromosome 6 for body weight at 16 weeks. Across the entire data set, RHM identified more regions reaching the suggestive level than GWA, suggesting that RHM is capable of capturing some of the variation not detected by GWA analyses.

Genetic factors controlling wool shedding in a composite Easycare sheep flock.

Historically, sheep have been selectively bred for desirable traits including wool characteristics. However, recent moves towards extensive farming and reduced farm labour have seen a renewed interest in Easycare breeds. The aim of this study was to quantify the underlying genetic architecture of wool shedding in an Easycare flock. Wool shedding scores were collected from 565 pedigreed commercial Easycare sheep from 2002 to 2010. The wool scoring system was based on a 10-point (0-9) scale, with score 0 for animals retaining full fleece and 9 for those completely shedding. DNA was sampled from 200 animals of which 48 with extreme phenotypes were genotyped using a 50-k SNP chip. Three genetic analyses were performed: heritability analysis, complex segregation analysis to test for a major gene hypothesis and a genome-wide association study to map regions in the genome affecting the trait. Phenotypes were treated as a continuous or binary variable and categories. High estimates of heritability (0.80 when treated as a continuous, 0.65-0.75 as binary and 0.75 as categories) for shedding were obtained from linear mixed model analyses. Complex segregation analysis gave similar estimates (0.80 ± 0.06) to those above with additional evidence for a major gene with dominance effects. Mixed model association analyses identified four significant (P < 0.05) SNPs. Further analyses of these four SNPs in all 200 animals revealed that one of the SNPs displayed dominance effects similar to those obtained from the complex segregation analyses. In summary, we found strong genetic control for wool shedding, demonstrated the possibility of a single putative dominant gene controlling this trait and identified four SNPs that may be in partial linkage disequilibrium with gene(s) controlling shedding.

Defining peripherally inserted central catheter tip position and an evaluation of insertions in one unit.

Peripherally inserted central catheters are increasingly used to provide access to the central venous circulation. They are commonly positioned 'blind' using a variety of anthropometric techniques and operator experience to direct insertion length. Malposition rates are poorly defined because of differing insertion techniques, difficulties defining anatomical tip position on chest radiographs, controversy over what constitutes an adequate catheter position and possible differences between patient groups. We have developed a reproducible method to define catheter positions on chest radiograph and have applied this in a retrospective analysis of 256 ICU and 243 non-ICU catheter insertions over a 6-month period. Two different definitions were used for adequate position. 'Blind' positioning of peripherally inserted central catheters was associated with a definition-dependent malposition rate of 42-76%. Malposition rates were significantly higher in ICU patients. Emerging technologies may assist in reducing these high rates.

Hindered proton collectivity in 16(28)S12: possible magic number at Z=16.

The reduced transition probability B(E2;0(gs)(+)→2(1)(+)) for (28)S was obtained experimentally using Coulomb excitation at 53 MeV/nucleon. The resultant B(E2) value 181(31) e(2)fm(4) is smaller than the expectation based on empirical B(E2) systematics. The double ratio |M(n)/M(p)|/(N/Z) of the 0(gs)(+)→2(1)(+) transition in (28)S was determined to be 1.9(2) by evaluating the M(n) value from the known B(E2) value of the mirror nucleus (28)Mg, showing the hindrance of proton collectivity relative to that of neutrons. These results indicate the emergence of the magic number Z=16 in the |T(z)|=2 nucleus (28)S.

Identification of polymorphisms in the malic enzyme 1, NADP(+)-dependent, cytosolic and nuclear receptor subfamily 0, group B, member 2 genes and their associations with meat and carcass quality traits in commercial Angus cattle.

Genes involved in the physiological control of energy and triglyceride synthesis, such as malic enzyme 1, NADP(+)-dependent, cytosolic (ME1) and nuclear receptor subfamily 0, group B, member 2 (NR0B2), are key candidates that may have effects on meat and carcass quality traits. These genes were sequenced in Aberdeen Angus beef cattle, and the possibility of associations between SNPs and economically important carcass and meat quality traits was tested. Six novel SNPs, five in ME1 and one in NR0B2, were identified. A SNP in exon eight of ME1 resulted in a non-synonymous amino acid change from valine to isoleucine. Phenotypic data were recorded on 536 commercial Aberdeen Angus-cross beef cattle, which comprised 28 carcass quality, tenderness and sensory traits. The majority of the SNPs were associated with at least one of these traits, including an association between the NR0B2 SNP and fat class, and associations between at least one of the ME1 SNPs and eye muscle area, sirloin weight before maturation, sirloin steak tail length, and juiciness.

Detection of quantitative trait loci for resistance to gastrointestinal nematode infections in Creole goats.

This study aimed to identify regions of the genome affecting resistance to gastrointestinal nematodes in a Creole goat population naturally exposed to a mixed nematode infection (Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum) by grazing on irrigated pasture. A genome-wide quantitative trait loci (QTL) scan was performed on 383 offspring from 12 half-sib families. A total of 101 microsatellite markers were genotyped. Traits analysed were faecal egg count (FEC), packed cell volume (PCV), eosinophil count and bodyweight (BW) at 7 and 11 months of age. Levels of activity of immunoglobulin A (IgA) and activity of immunoglobulin E (IgE) anti-Haemonchus contortus L3 crude extracts and adult excretion/secretion products (ESPs) were also analysed. Using interval mapping, this study identified 13 QTL for parasite resistance. Two QTL linked with FEC were found on chromosomes 22 and 26. Three QTL were detected on chromosomes 7, 8 and 14 for eosinophil counts. Three QTL linked with PCV were identified on chromosomes 5, 9 and 21. A QTL for BW at 7 months of age was found on chromosome 6. Lastly, two QTL detected on chromosomes 3 and 10 were associated with IgE anti-L3, and IgE anti-ESP was linked with two QTL on chromosomes 1 and 26. This study is the first to have identified regions of the genome linked with nematode resistance in a goat population using a genome scan. These results provide useful tools for the understanding of parasite resistance in small ruminants.

The identification of SNPs with indeterminate positions using the Equine SNP50 BeadChip.

We have used linkage disequilibrium (LD) to identify single nucleotide polymorphisms (SNPs) on the Illumina Equine SNP50 BeadChip, which may be incorrectly positioned on the genome map. A total of 1201 Thoroughbred horses were genotyped using the Illumina Equine SNP50 BeadChip. LD was evaluated in a pairwise fashion between all autosomal SNPs, both within and across chromosomes. Filters were then applied to the data, firstly to identify SNPs that may have been mapped to the wrong chromosome and secondly to identify SNPs that may have been incorrectly positioned within chromosomes. We identified a single SNP on ECA28, which showed low LD with neighbouring SNPs but considerable LD with a group of SNPs on ECA10. Furthermore, a cluster of SNPs on ECA5 showed unusually low LD with surrounding SNPs. A total of 39 SNPs met the criteria for unusual within-chromosome LD. The results of this study indicate that some SNPs may be misplaced. This finding is significant, as misplaced SNPs may lead to difficulties in the application of genomic methods, such as homozygosity mapping, for which SNP order is important.

Warm autoadsorption with enzyme-treated red blood cells.

Patients demonstrating warm autoantibody specificity present serologic challenges for laboratory staff performing antibody identification in the blood bank. Autoantibody can be removed from plasma or serum by adsorption onto autologous red blood cells (RBCs) provided the patient has not been transfused in the previous 3 months. The adsorption process can be enhanced by enzyme pretreatment of autologous RBCs.

Estimation of historical effective population size using linkage disequilibria with marker data.

Theory hypothesizes that the rate of decline in linkage disequilibrium (LD) as a function of distance between markers, measured by r(2), can be used to estimate effective population size (N(e)) and how it varies over time. The development of high-density genotyping makes feasible the application of this theory and has provided an impetus to improve predictions. This study considers the impact of several developments on the estimation of N(e) using both simulated and equine high-density single-nucleotide polymorphism data, when N(e) is assumed to be constant a priori and when it is not. In all models, estimates of N(e) were highly sensitive to thresholds imposed upon minor allele frequency (MAF) and to a priori assumptions on the expected r(2) for adjacent markers. Where constant N(e) was assumed a priori, then estimates with the lowest mean square error were obtained with MAF thresholds between 0.05 and 0.10, adjustment of r(2) for finite sample size, estimation of a [the limit for r(2) as recombination frequency (c) approaches 0] and relating N(e) to c (1 - c/2). The findings for predicting N(e) from models allowing variable N(e) were much less clear, apart from the desirability of correcting for finite sample size, and the lack of consistency in estimating recent N(e) (<7 generations) where estimates use data with large c. The theoretical conflicts over how estimation should proceed and uncertainty over where predictions might be expected to fit well suggest that the estimation of N(e) when it varies be carried out with extreme caution.

Hand hygiene behaviours monitored by an electronic system in the intensive care unit - a prospective observational study.

BACKGROUND: It is difficult to improve compliance with hand hygiene (HH), and underlying behaviours are not clearly understood among healthcare workers. AIM: To study HH behaviours among healthcare workers. METHODS: This was a prospective observational study. A Sanibit electronic HH system was installed in a 10-bed surgical intensive care unit (ICU) that detected HH opportunities automatically when healthcare workers entered or exited a patient room, and tracked the HH compliance of healthcare workers. The HH compliance rate and patient contact time were calculated and analysed at both ICU level and individual level over time. FINDINGS: In total, 27,692 HH opportunities were recorded over this 6-month trial period. The HH compliance rate was significantly higher when healthcare workers exited patient rooms than when they entered patient rooms (37.3% vs 26.1%; P<0.001). Full, partial and total HH compliance rates of 'quick in and quick out' (in room for <3 s) events were significantly lower than those of 'long in and long out' (in room for >30 s) events (23.45% vs 32.77%, 21.44% vs 35.03% and 44.88% vs 67.81%, respectively; P<0.001). There were also significant differences in HH compliance between individual healthcare workers (P<0.001). No significant differences in overall HH compliance rate and patient contact time were found between hours of the day or days of the week, except partial HH compliance rates. CONCLUSION: Patterns of HH behaviours among healthcare workers are complex and variable, which could facilitate targeted and personalized interventions to improve HH compliance. CLINICAL TRIAL REGISTRATION: NCT03948672.

Defining in Detail and Evaluating Reliability of DSM-5 Criteria for Autism Spectrum Disorder (ASD) Among Children.

This paper describes a process to define a comprehensive list of exemplars for seven core Diagnostic and Statistical Manual (DSM) diagnostic criteria for autism spectrum disorder (ASD), and report on interrater reliability in applying these exemplars to determine ASD case classification. Clinicians completed an iterative process to map specific exemplars from the CDC Autism and Developmental Disabilities Monitoring (ADDM) Network criteria for ASD surveillance, DSM-5 text, and diagnostic assessments to each of the core DSM-5 ASD criteria. Clinicians applied the diagnostic exemplars to child behavioral descriptions in existing evaluation records to establish initial reliability standards and then for blinded clinician review in one site (phase 1) and for two ADDM Network surveillance years (phase 2). Interrater reliability for each of the DSM-5 diagnostic categories and overall ASD classification was high (defined as very good .60-.79 to excellent ≥ .80 Kappa values) across sex, race/ethnicity, and cognitive levels for both phases. Classification of DSM-5 ASD by mapping specific exemplars from evaluation records by a diverse group of clinician raters is feasible and reliable. This framework provides confidence in the consistency of prevalence classifications of ASD and may be further applied to improve consistency of ASD diagnoses in clinical settings.