Metabolic profile and gene expression pattern of cytokines and antioxidants markers during different physiological stages in Barki ewes.

BACKGROUND: In livestock, identifying the physiological and reproductive stages is valuable in guiding management decisions related to nutrition, veterinary procedures, and breeding programs. To achieve this goal, a cohort of Barki ewes in this research underwent observation across three pivotal physiological conditions: pre-pregnancy, late pregnancy, and early lactation. Blood samples were collected to investigate the changes in serum metabolic profile as well as gene expression pattern of cytokines and antioxidants markers during these stages. RESULTS: Our results showed that during late pregnancy, there was a significant (P < 0.05) increase in red blood cells (11.9 ± 0.5 1012/L), hemoglobin (10.8 ± 0.4 g/dl) and neutrophils count (7 ± 0.1 109/L) with significant decrease (P < 0.05) of total white blood cell count (9.1 ± 0.05 109/L). The packed cell volume (%) and monocyte count showed a significant (P < 0.05) decrease during both late pregnancy and early lactation stages. The serum concentrations of glucose, cholesterol, GSH, GPx, SOD and catalase displayed significant (P < 0.05) decrease during late pregnancy and early-lactation. Notably, during late pregnancy, there was a significant (P < 0.05) increase in the serum concentrations of albumin, globulin, urea, IGF-1, and malondialdehyde with significant decrease (P < 0.05) of total protein (4.9 ± 0.08 g/dl). Additionally, during early lactation, there was a significant (P < 0.05) increase in the serum levels of non-esterified fatty acids, triiodothyronine (T3), and thyroxin (T4). The gene expression profiles of cytokines (IL-4, IL-6, IL-8, and NFKB) were decreased in the ewes during late pregnancy compared to pre-pregnant and early lactation stages. In addition, the expression profile of antioxidant genes (SOD, CAT, GPX, and Nrf2) was significantly upsurged in the non-pregnant ewes compared to late pregnancy and early lactation ones. CONCLUSIONS: The results concluded that different physiological status significantly affects the blood metabolic profile and gene expression pattern in Barki sheep. Our findings can be helpful in monitoring animal health and applying in breeding programs of Barki sheep under harsh environmental conditions.

Comparative study of laparoscopic ventral mesh rectopexy versus perineal stapler resection for external full-thickness rectal prolapse in elderly patients: enhanced outcomes and reduced recurrence rates-a retrospective cohort study.

BACKGROUND: In elderly patients with external full-thickness rectal prolapse (EFTRP), the exact differences in postoperative recurrence and functional outcomes between laparoscopic ventral mesh rectopexy (LVMR) and perineal stapler resection (PSR) have not yet been investigated. METHODS: We conducted a retrospective multicenter study on 330 elderly patients divided into LVMR group (n = 250) and PSR (n = 80) from April 2012 to April 2019. Patients were evaluated before and after surgery by Wexner incontinence scale, Altomare constipation scale, and patient satisfaction questionnaire. The primary outcomes were incidence and risk factors for EFTRP recurrence. Secondary outcomes were postoperative incontinence, constipation, and patient satisfaction. RESULTS: LVMR was associated with fewer postoperative complications (p < 0.001), lower prolapse recurrence (p < 0.001), lower Wexner incontinence score (p = 0.03), and lower Altomare's score (p = 0.047). Furthermore, LVMR demonstrated a significantly higher surgery-recurrence interval (p < 0.001), incontinence improvement (p = 0.019), and patient satisfaction (p < 0.001) than PSR. Three and 13 patients developed new symptoms in LVMR and PSR, respectively. The predictors for prolapse recurrence were LVMR (associated with 93% risk reduction of recurrence, OR 0.067, 95% CI 0.03-0.347, p = 0.001), symptom duration (prolonged duration was associated with an increased risk of recurrence, OR 1.131, 95% CI 1.036-1.236, p = 0.006), and length of prolapse (increased length was associated with a high recurrence risk (OR = 1.407, 95% CI = 1.197-1.655, p < 0.001). CONCLUSIONS: LVMR is safe for EFTRP treatment in elderly patients with low recurrence, and improved postoperative functional outcomes. TRIAL REGISTRATION: Clinical Trial.gov (NCT05915936), retrospectively registered on June 14, 2023.

Percutaneous Ilioilial Fixator Versus Percutaneous Iliosacral Screw in Managing Unstable Sacral Fractures: A Prospective Randomised Controlled Study.

INTRODUCTION: Unstable sacral fractures with pelvic fractures are challenging to both surgeons and patients, particularly in the immediate post-injury phase and later when definitive fixation is undertaken. Percutaneous iliosacral screw fixation is widely regarded as the gold standard treatment for unstable sacral fractures without spinopelvic dissociation. Closed reduction and percutaneous fixation using iliosacral screws for sacral fractures provide early stabilisation without the need for extensive surgical exposure, thereby mitigating major complications associated with open surgical procedures. A new technique for stabilising unstable sacral fractures is the minimally invasive ilioilial fixator, also called a transiliac internal fixator (TIIF), which has gained more attention for its ability to address challenges associated with sacroiliac screw fixation. The objective of this study is to compare the functional, radiological, and surgical outcomes between the percutaneous iliosacral screw and the ilioilial fixator. METHODS: A total of 51 patients with sacral fracture injuries sustained between August 2019 and November 2021 were included in this study, with 25 patients in Group A and 26 patients in Group B. Patient randomization was done using computer-generated randomization facilitated by Random Allocation Software (Mahmood Saghaei, Isfahan, Iran). All patients underwent the chosen intervention within 10 days of the trauma. Patients had follow-up at two weeks, six weeks, and 12 months post-treatment. The results of fixation were evaluated radiologically based on the Matta and Tornetta grading system and clinically using the Majeed pelvic scoring system. Complications were detected in both groups during follow-up visits. RESULTS: The study found no statistically significant differences between the two patient groups in terms of final clinical assessment (p=0.79), radiological assessment (p=0.78), or the need for another operation (p=1.0). Moreover, there were no statistically significant differences between the groups with respect to complication rates (p=0.63) or the time of union (p=0.14). No differences were noted in terms of intraoperative blood loss (p=0.93) or operative time (p=0.34) but for longer incision length in the ilioilial fixator group (p<0.001) and an increased risk of intraoperative radiation exposure in the iliosacral screw group (p<00.1). DISCUSSION: Although the iliosacral screw is considered a gold standard for unstable sacral fracture, a TIIF is a good alternative with a very satisfactory outcome. CONCLUSION: Although the iliosacral screw still remains the gold standard for the management of sacral fractures, the ilioilial fixator emerges as a good alternative with comparable functional and radiological outcomes.

New insights into the genetic predisposition of brucellosis and its effect on the gut and vaginal microbiota in goats.

Goats contribute significantly to the global food security and industry. They constitute a main supplier of meat and milk for large proportions of people in Egypt and worldwide. Brucellosis is a zoonotic infectious disease that causes a significant economic loss in animal production. A case-control genome-wide association analysis (GWAS) was conducted using the infectious status of the animal as a phenotype. The does that showed abortion during the last third period of pregnancy and which were positive to both rose bengal plate and serum tube agglutination tests, were considered as cases. Otherwise, they were considered as controls. All animals were genotyped using the Illumina 65KSNP BeadChip. Additionally, the diversity and composition of vaginal and fecal microbiota in cases and controls were investigated using PCR-amplicone sequencing of the V4 region of 16S rDNA. After applying quality control criteria, 35,818 markers and 66 does were available for the GWAS test. The GWAS revealed a significantly associated SNP (P = 5.01 × 10-7) located on Caprine chromosome 15 at 29 megabases. Four other markers surpassed the proposed threshold (P = 2.5 × 10-5). Additionally, fourteen genomic regions accounted for more than 0.1% of the variance explained by all genome windows. Corresponding markers were located within or in close vicinity to several candidate genes, such as ARRB1, RELT, ATG16L2, IGSF21, UBR4, ULK1, DCN, MAPB1, NAIP, CD26, IFIH1, NDFIP2, DOK4, MAF, IL2RB, USP18, ARID5A, ZAP70, CNTN5, PIK3AP1, DNTT, BLNK, and NHLRC3. These genes play important roles in the regulation of immune responses to the infections through several biological pathways. Similar vaginal bacterial community was observed in both cases and controls while the fecal bacterial composition and diversity differed between the groups (P < 0.05). Faeces from the control does showed a higher relative abundance of the phylum Bacteroidota compared to cases (P < 0.05), while the latter showed more Firmicutes, Spirochaetota, Planctomycetota, and Proteobacteria. On the genus level, the control does exhibited higher abundances of Rikenellaceae RC9 gut group and Christensenellaceae R-7 group (P < 0.05), while the infected does revealed higher Bacteroides, Alistipes, and Prevotellaceae UCG-003 (P < 0.05). This information increases our understanding of the genetics of the susceptibility to Brucella in goats and may be useful in breeding programs and selection schemes that aim at controlling the disease in livestock.

Genome-wide landscape of runs of homozygosity and differentiation across Egyptian goat breeds.

Understanding the genomic features of livestock is essential for successful breeding programs and conservation. This information is scarce for local goat breeds in Egypt. In the current study, genomic regions with selection signatures were identified as well as runs of homozygosity (ROH), genomic inbreeding coefficients (FROH) and fixation index (FST) were detected in Egyptian Nubian, Damascus, Barki and Boer goat breeds. A total of 46,268 SNP markers and 337 animals were available for the genomic analyses. On average, 145.44, 42.02, 87.90 and 126.95 ROHs were detected per individual in the autosomal genome of the respective breeds. The mean accumulative ROH lengths ranged from 46.5 Mb in Damascus to 360 Mb in Egyptian Nubian. The short ROH segments (< 2 Mb) were most frequent in all breeds, while the longest ROH segments (> 16 Mb) were exclusively found in the Egyptian Nubian. The highest average FROH was observed in Egyptian Nubian (~ 0.12) followed by Boer (~ 0.11), while the lowest FROH was found in Damascus (~ 0.05) and Barki breed (~ 0.03). The estimated mean FST was 0.14 (Egyptian Nubian and Boer), 0.077 (Egyptian Nubian and Barki), 0.075 (Egyptian Nubian and Damascus), 0.071 (Barki and Boer), 0.064 (Damascus and Boer), and 0.015 (Damascus and Barki), for each pair of breeds. Interestingly, multiple SNPs that accounted for high FST values were observed on chromosome 6 in regions harboring ALPK1 and KCNIP4. Genomic regions overlapping both FST and ROH harbor genes related to immunity (IL4R, PHF23, GABARAP, GPS2, and CD68), reproduction (SPATA2L, TNFSF12, TMEM95, and RNF17), embryonic development (TCF25 and SOX15) and adaptation (MC1R, KDR, and KIT), suggesting potential genetic adaptations to local environmental conditions. Our results contribute to the understanding of the genetic architecture of different goat breeds and may provide valuable information for effective preservation and breeding programs of local goat breeds in Egypt.

Intraoperative endomanometric laparoscopic Nissen fundoplication improves postoperative outcomes in large sliding hiatus hernias with severe gastroesophageal reflux disease: a retrospective cohort study.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the gold standard surgical intervention for gastroesophageal reflux disease (GERD). LNF can be followed by recurrent symptoms or complications affecting patient satisfaction. The aim of this study is to assess the value of the intraoperative endomanometric evaluation of esophagogastric competence and pressure combined with LNF in patients with large sliding hiatus hernia (>5 cm) with severe GERD (DeMeester score >100). MATERIALS AND METHODS: This is a retrospective, multicenter cohort study. Baseline characteristics, postoperative dysphagia and gas bloat syndrome, recurrent symptoms, and satisfaction were collected from a prospectively maintained database. Outcomes analyzed included recurrent reflux symptoms, postoperative side effects, and satisfaction with surgery. RESULTS: Three hundred sixty patients were stratified into endomanometric LNF (180 patients, LNF+) and LNF alone (180 patients, LNF). Recurrent heartburn (3.9 vs. 8.3%) and recurrent regurgitation (2.2 vs. 5%) showed a lower incidence in the LNF+ group ( P =0.012). Postoperative score III recurrent heartburn and score III regurgitations occurred in 0 vs. 3.3% and 0 vs. 2.8% cases in the LNF+ and LNF groups, respectively ( P =0.005). Postoperative persistent dysphagia and gas bloat syndrome occurred in 1.75 vs. 5.6% and 0 vs. 3.9% of patients ( P =0.001). Score III postoperative persistent dysphagia was 0 vs. 2.8% in the two groups ( P =0.007). There was no redo surgery for dysphagia after LNF+. Patient satisfaction at the end of the study was 93.3 vs. 86.7% in both cohorts, respectively ( P =0.05). CONCLUSIONS: Intraoperative high-resolution manometry and endoscopic were feasible in all patients, and the outcomes were favorable from an effectiveness and safety standpoint.

Variation in the ovine FOXP3 gene and its effect on growth traits in Egyptian Barki sheep.

The aim of the present study was to detect the FOXP3 gene polymorphisms in Barki sheep at a variable region covering exon 13, intron 13 and the coding sequence in exon 14 and to test the association of these polymorphisms with growth traits. 122 Barki lambs were phenotyped for various growth traits, viz., birth weight (BW), weaning weight (WW), pre-weaning daily gain in weight (ADG1), post-weaning daily gain in weight (ADG2) and marketing bodyweight (MW). The polymerase chain reaction - single-strand conformational polymorphisms (PCR-SSCP) and DNA sequencing methods were used to identify the genetic variants in the FOXP3 gene. The associations between the variation in FOXP3 gene and growth traits were tested using a general linear model. Two variants (F1 and F2 with gene frequencies of 0.64 and 0.36, respectively), and three genotypes (F1F1, F1F2 and F2F2 with frequencies of 0.37, 0.53 and 0.10, respectively) were detected. The association of FOXP3 genotype was significant (p < 0.05) with ADG2 and MW. It is concluded that FOXP3 genotype might be helpful for sheep breeders to produce fast-growing lambs. However, further studies are needed in a large population to confirm the association we found.

Genetic variation in the ovine KAP22-1 gene and its effect on wool traits in Egyptian sheep.

The objective of this study was to investigate the genetic polymorphisms in the keratin-associated protein (KAP22-1) gene in Barki ( n = 206 ), Rahmani ( n = 28 ) and Ossimi ( n = 28 ) as the three major sheep breeds in Egypt. Subsequently, the detected variants were correlated with important wool traits. The traits included greasy fleece weight (GFW, g), staple length (SL, cm), prickle factor (PF, %), medullated fiber (MF, %), fiber diameter (FD, µ m), crimp percentage (CR, %) and the standard deviation of FD (SD fd , µ m), as well as the subjectively assessed traits of kemp score (KS), handle grade (HG), greasy color grade (GCG), bulk grade (BG), luster grade (LG) and staple structure (SST). Animals were genotyped by polymerase chain reaction (PCR) - single strand conformation polymorphism (SSCP). Five SSCP banding patterns representing three different nucleotide variants (A, B and C) were detected. DNA sequencing confirmed three single nucleotide polymorphisms (SNPs). Animal age significantly affected GFW ( P = 0.007 ), SD fd ( P = 0.006 ), SL ( P = 0.002 ), CR ( P = 0.006 ), KS ( P = 0.001 ), LG ( P = 0.006 ) and SST ( P = 0.013 ). Likewise, the breed had a significant effect on all studied traits except HG and BG, which was not significant. Results showed significant associations between the KAP22-1 variants and CR ( P = 0.01 ), SL ( P = 0.012 ), KS ( P < 0.001 ) and GCG ( P = 0.01 ). Interestingly, animals with BB genotypes tended to produce more wool yield ( 1163.63 ± 65.91  g) with high SL ( 8.38 ± 0.20  cm), CR ( 8.38 ± 0.21  %) and KS ( 1.98 ± 1.88 ). Results of this study strongly recommend the KAP22-1 gene as a candidate gene for wool production traits in Egyptian sheep, with new useful insights into the visually assessed wool traits. The identified genetic markers may be incorporated into breeding strategies and genetic improvement programs of wool traits in Egyptian sheep.

Recurrent appendicitis following successful drainage of appendicular abscess in adult without interval appendectomy during COVID-19. Prospective cohort study.

BACKGROUND: COVID-19 infection is a global pandemic that affected routine health services and made patients fear to consult for medical health problems, even acute abdominal pain. Subsequently, the incidence of complicated appendicitis increased during the Covid-19 pandemic. This study aimed to evaluate recurrent appendicitis after successful drainage of appendicular abscess during COVID-19. MATERIAL AND METHODS: A prospective cohort study conducted in the surgical emergency units of our Universities' Hospitals between March 15, 2020 to August 15, 2020 including patients who were admitted with the diagnosis of an appendicular abscess and who underwent open or radiological drainage. Main outcomes included incidence, severity, and risk factors of recurrent appendicitis in patients without interval appendectomy. RESULTS: A total of 316 patients were included for analysis. The mean age of the patients was 37 years (SD ± 13). About two-thirds of patients were males (60.1%). More than one-third (39.6%) had co-morbidities; type 2 diabetes mellitus (T2DM) (22.5%) and hypertension (17.1%) were the most frequent. Approximately one quarter (25.6%) had confirmed COVID 19 infection. About one-third of the patients (30.4%) had recurrent appendicitis. More than half of them (56.3%) showed recurrence after three months, and 43.8% of patients showed recurrence in the first three months. The most frequent grade was grade I (63.5%). Most patients (77.1%) underwent open surgery. Age, T2DM, hypertension, COVID-19 infection and abscess size >3 cm were significantly risking predictors for recurrent appendicitis. CONCLUSIONS: Interval appendectomy is suggested to prevent 56.3% of recurrent appendicitis that occurs after 3 months. We recommend performing interval appendectomy in older age, people with diabetes, COVID-19 infected, and abscesses more than 3 cm in diameter. RESEARCH QUESTION: Is interval appendectomy preventing a high incidence of recurrent appendicitis after successful drainage of appendicular abscess during COVID-19 pandemic?

The efficacy of wrapping the neurorrhaphy site utilizing dura substitute: A case series.

BACKGROUND: Different procedures have been developed to improve the surgical outcome of peripheral nerve injuries. The purpose of this study was to evaluate the efficacy of wrapping the neurorrhaphy site utilizing dura substitute graft as an alternative conduit in the management of peripheral nerve injury. METHODS: This retrospective clinical case series included 42 patients with a single peripheral nerve injury. The mean age was 26.8 ± 11 years, and the mean duration of symptoms was 3 ± 1.8 months. The visual analogue score (VAS) for pain and the Medical Research Council's (MRC) grading for motor power were used to evaluate the functional outcome among our patients. All patients were operated on for primary microscopic end-to-end repair, followed by wrapping the neurorrhaphy site with dura substitute graft as a conduit. Patients were followed in the outpatient clinic with regular visits for average of 6 months. RESULTS: Thirty-seven patients (83%), showed functional improvement in all aspects, the VAS for pain and the MRC for motor power, as well as the functional state. One patient (2.3%) developed a postoperative hematoma collection, which needed immediate evacuation. Superficial wound infection, reported in two patients (4.7%), was treated conservatively. No postoperative neuroma was observed among our patients during the follow-up period. CONCLUSION: Wrapping the neurorrhaphy site utilizing dura substitute as conduit appears to be safe and might prove effective in managing peripheral nerve injury.

Genetic variations in the Myostatin gene affecting growth traits in sheep.

BACKGROUND AND AIM: Sheep productivity in developing countries is crucial, as this animal is an essential source of meat and wool. Myostatin (MSTN) plays an important role in the regulation of muscle mass through the regulation of muscle growth, differentiation, and regeneration. The present study sought to investigate genetic variation in the first intron of the MSTN gene and the association of variants with growth traits in major sheep breeds in Egypt (Barki, Ossimi, and Rahmani) and Saudi Arabia (Najdi) using polymerase chain reaction (PCR) and sequencing. MATERIALS AND METHODS: Blood samples were collected, and DNA was extracted from 75 animals. A 386 bp fragment in the first intron of the MSTN gene was amplified using PCR. Polymorphic sites were detected using direct sequencing and then correlated with growth traits using a general linear model. RESULTS: Sequence analysis of the first intron of MSTN gene identified six single-nucleotide polymorphisms (SNPs) in the studied breeds. Four mutual SNPs were determined: c.18 G>T, c.241 T>C, c.243 G>A, and c.259 G>T. In addition, two SNPs c.159 A>T and c.173 T>G were monomorphic (AA and TT, respectively) in the Ossimi, Rahmani, and Najdi breeds and polymorphic in the Barki breed. The association analysis revealed that the c.18 G>T and c.241 C>T significantly associated (p<0.05) with birth weight and average daily weight gain, respectively. CONCLUSION: Our results strongly support MSTN as a candidate gene for marker-assisted selection in sheep breeding programs. Furthermore, the identified variants may be considered as putative markers to improve growth traits in sheep.

A missense mutation in the coding region of the toll-like receptor 4 gene affects milk traits in Barki sheep.

OBJECTIVE: Milk production is one of the most desirable traits in livestock. Recently, the toll-like receptor (TLR) has been identified as a candidate gene for milk traits in cows. So far, there is no information concerning the contribution of this gene in milk traits in sheep. This study was designed to investigate the TLR 4 gene polymorphisms in Barki ewes in Egypt and then correlate that with milk traits in order to identify potential single nucleotide polymorphisms (SNPs) for these traits in sheep. METHODS: A part of the ovine TLR 4 gene was amplified in Barki ewes, to identify the SNPs. Consequently; Barki ewes were genotyped using polymerase chain reaction-single strand conformation polymorphism protocol. These genotypes were correlated with milk traits, which were the daily milk yield (DMY), protein percentage (PP), fat percentage (FP), lactose percentage, and total solid percentage (TSP). RESULTS: Age and parity of the ewe had a significant effect (p<0.05 or p<0.01) on DMY, FP, and TSP. The direct sequencing identified a missense mutation located in the coding sequence of the gene (rs592076818; c.1710C>A) and was predicted to change the amino acid sequence of the resulted protein (p.Asn570Lys). The association analyses suggested a significant effect (p<0.05) of the TLR genotype on the FP and PP, while the DMY tended to be influenced as well (p = 0.07). Interestingly, the presence of the G allele tended to increase the DMY (+40.5 g/d) and significantly (p<0.05 or p<0.01) decreased the FP (-1.11%), PP (-1.21%), and TSP (-7.98%). CONCLUSION: The results of this study suggested the toll-like receptor 4 (TLR4) as a candidate gene to improve milk traits in sheep worldwide, which will enhance the ability to understand the genetic architecture of genes underlying SNPs that affect such traits.

Genetic evaluation of growth in Barki sheep using random regression models.

The objective of the current study was to estimate covariance components of growth at different ages from birth to yearling in Barki lambs. A total of 16,496 records for body weights at birth (W0), 3 (W3), 6 (W6), 9 (W9), and 12 (12) months of age for Barki lambs were available. Two statistical approaches were used; multi-trait (MT) and random regression (RR) animal models assuming two random effects only, additive genetic effect (σ2a) and permanent environmental effect (σ2pe) of the animal. Regarding the RR model, Legendre polynomials (LP) of different orders for the random parts were compared in order to evaluate the most appropriate model. Bayesian information and Akaike information criteria suggested that the optimal RR model included the third order for fixed effect of lamb age and σ2pe, and fourth order of LP for σ2a (LP343). Estimates of direct heritability (h2a) from LP343 showed an ascending pattern, as it was 0.06 ± 0.03 for birth weight and reached to the peak at 9 months (0.42 ± 0.02). Thereafter, it declined again at the end of trajectory (12 months of age; 0.27 ± 0.03). The MT model showed a fluctuated pattern and lower estimates of h2a (0.19 ± 0.03, 0.11 ± 0.02, 0.12 ± 0.02, 0.11 ± 0.03, and 0.16 ± 0.04 for W0, W3, W6, W9, and W12, respectively). Considerably, similar ascending patterns of the ratio of σ2pe to phenotypic variance were reported from both RR (from 3 to 50%) and MT models (from 5 to 20%). Of interest, the RR model showed higher predicting ability of the breeding values compared with the MT model, which is an indicator for the suitability of RR models for analyzing the consecutive growth traits in sheep. Results suggested that the Barki sheep has a potential for genetic selection based on weight at different ages with selection likely to be more efficient at 9 months of age.

A positional candidate gene association analysis of susceptibility to paratuberculosis on bovine chromosome 7.

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative pathogen for paratuberculosis, which is a chronic inflammation of the small intestine in ruminants and some wild animals. It affects negatively on the economics of dairy operations worldwide and has a zoonotic concern for its potential relationship to Crohn's disease in humans. In this study, we used different approaches to investigate genetic markers associated with MAP infection on bovine chromosome 7. The interleukin-2-inducible T-cell kinase (ITK) gene is a non-receptor tyrosine kinase expressed in T cells, which also is involved in regulation and development of immune cells and some inflammatory diseases. The gene was suggested in a previous GWAS analysis as a positional candidate gene located on BTA7 for MAP infection. In this study, bovine ITK was sequenced and seventeen identified SNPs were genotyped in 1419 Holstein and Jersey cows. Association analysis revealed no significantly associated SNP in the bovine ITK gene using either single marker or haplotype analyses. In a complementary analysis, Holstein genotypes were imputed from 50 K SNPs to the full genome sequence of BTA7. Single SNP association tests identified two SNPs at 15 Mb (p = 5 × 10-7) significantly associated with MAP infection. Our results suggest an additional region of BTA7 contributes to susceptibility to MAP infection in cattle, relative to our previous report, and further investigations are required.

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.