Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis.

INTRODUCTION AND OBJECTIVES: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fHP. MATERIAL AND METHODS: A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls. RESULTS: MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73-27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP. CONCLUSION: These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.

Inheritance of genomic regions and genes associated with number of oocytes and embryos in Gir cattle through daughter design.

Over the past decades, daughter designs, including genotyped sires and their genotyped daughters, have been used as an approach to identify quantitative trait loci (QTL) related with economic traits. The aim of this study was to identify genomic regions inherited by Gir sire families and genes associated with number of viable oocytes (VO), total number of oocytes (TO) and number of embryos (EMBR) based on a daughter design approach. In total, 15 Gir sire families were selected. The number of daughters per family ranged from 26 to 395, which were genotyped with different SNP panels and imputed to the Illumina BovineHD BeadChip (777K) and had phenotypes for oocyte and embryo production. Daughters had phenotypic data for VO, TO, and EMBR. The search for QTL was performed through Genome-Wide Association Study (GWAS) based on genomic best linear unbiased prediction (gBLUP). QTL were found for each trait among and within families based on the top 10 genomic windows with the greatest genetic variance. For EMBR, genomic windows identified among families were located on BTA4, BTA5, BTA6, BTA7, BTA8, BTA13, BTA16 and BTA17, and they were most frequent on BTA7 within families. For VO, genomic windows were located on BTA2, BTA4, BTA5, BTA7, BTA17, BTA21, BTA22, BTA23 and BTA27 among families, being most frequent on BTA8 within families. For TO, top 10 genomic windows were identified on BTA2, BTA4, BTA5, BTA7, BTA17, BTA21, BTA22, BTA26 and BTA27, being most frequent on BTA7 and BTA8 within families. Considering all results, the greatest number of genomic windows was found on BTA7, where VCAN, XRCC4, TRNAC-ACA, HAPLN1 and EDIL3 genes were identified in the common regions. In conclusion, 15 Gir sire families with 26 to 395 daughters per family with phenotypes for oocyte and embryo production helped to identify the inheritance of several genomic regions, especially on BTA7, where EDIL3, HAPLN1 and VCAN candidate genes were associated with number of oocytes and embryos in Gir cattle families.

The impact of FSH stimulation and age on the ovarian and uterine traits and histomorphometry of prepubertal gilts.

This study investigated the effect of age and follicle stimulating hormone (FSH) treatment on the estradiol (E2) plasma concentration, ovarian follicle development, endometrial histomorphometry, and ultrasonographic parameters of the ovaries and uterus in prepubertal gilts. Thirty-five prepubertal gilts were grouped according to age (140 or 160 d), and within each age, gilts were allotted to receive 100 mg of FSH (treated; G140 + FSH [n = 10] and G160 + FSH [n = 7]) or saline solution (control; G140 + control [n = 10] and G160 + control [n = 8]). The total dose of FSH was divided into 6 similar doses administered every 8 h (days 0-2). Before and after FSH treatment, blood sample was collected, and transabdominal scanning of the ovaries and uterus was performed. Twenty-four hours after the last FSH injection, the gilts were slaughtered and their ovaries and uterus were processed for histological and histomorphometric analysis. The histomorphometric parameters of the uterus differed (P < 0.05) between prepubertal gilts at 160 d and 140 d of age. Moreover, changes (P < 0.05) in uterine and ovarian ultrasound images occurred between 140 and 160 d of age. Age and FSH treatment did not affect (P > 0.05) E2 plasma concentrations. Follicle stimulating hormone treatment did not affect (P > 0.05) the early stage of folliculogenesis in the prepubertal gilts; however, the number of early atretic follicles decreased (P < 0.05) after the FSH treatment. Follicle stimulating hormone administration increased (P < 0.05) the number of medium follicles and decreased (P < 0.05) the number of small follicles in 140 and 160 d old gilts. In the endometrium, luminal/glandular epithelium height and glandular diameter increased (P < 0.05) after FSH treatment. Thus, injections of 100 mg of FSH stimulate the endometrium epithelium and induce follicular growth to a medium follicle size without affecting the preantral stages in prepubertal gilts; also, the uterine macroscopic morphometry does not change from 140 to 160 d of age.

Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?

SUMMARY: We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up. LEARNING POINTS: The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.

Disruption of bovine sperm functions in the presence of aplastic midpiece defect.

BACKGROUND: Bulls are of great importance in the productive chain and for this reason they should have a good semen quality. There is no doubt that sperm morphology is very important to bull fertility, although little is known about how exactly the abnormal morphologies may affect sperm functions. OBJECTIVES: To detail the morphological description of the aplastic midpiece defect (AMD), as well as to understand its consequences for male fertility based on membrane and acrosome status, mitochondrial membrane potential and DNA integrity parameters. MATERIALS AND METHODS: The bulls were divided into two groups: control, consisting of satisfactory potential breeders (n = 3); and AMD, consisting of unsatisfactory potential breeders with a high percentage of AMD (n = 3). Bulls were evaluated by the breeding soundness evaluation; five ejaculates were collected from each animal and analyzed by flow cytometry. RESULTS: Spermatozoa from AMD group exhibited lower sperm motility and vigor (p < 0.05). In addition, it also exhibited lower mitochondrial membrane potential (p < 0.05), a higher percentage of spermatozoa with DNA fragmentation (p < 0.05), lower acrosome and plasma membrane integrity (p < 0.05), and higher lipid bilayer sperm membrane disorganization (p < 0.05) in comparison with control bulls. DISCUSSION: These findings may be due to oxidative stress and a reduction of the energy production capacity in addition to an alteration in the structural composition of the sperm cell. Moreover, semen with a high percentage of AMD may also be undergoing apoptosis. CONCLUSION: Bulls with a high percentage of AMD in their semen are not suitable for reproduction. Furthermore, it suggests there is a putative genetic basis for this sperm defect.

Hypersensitivity pneumonitis: Main features characterization in a Portuguese cohort.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) which varies in prevalence across the world, depending on disease definition, diagnostic methods, exposure type and intensity, geographical environments, agricultural and industrial practices, and host risk factors. This study aimed to deepen knowledge about HP's clinical characteristics, diagnosis and functional and imaging features in a cohort of HP patients from the North of Portugal. To achieve this goal, a retrospective assessment of the clinical and diagnostic data was carried out, and patients were classified and compared according to disease presentation (acute, sub-acute and chronic HP forms). Of the 209 HP patients included (mean age 58.3 ±â€¯16.0 years), 52.6% were female and 73.7% presented a chronic form. Most patients had prior exposure to birds (76.6%). Dyspnoea and cough were the most frequently experienced symptoms, but no statistically significant differences were found between groups (p = 0.089, p = 0.418, respectively). Fever was most common in acute HP form (p < 0.001). The most common patterns found in Chest CT were ground glass (p = 0.002) in acute/subacute presentation, and reticulation (p < 0.001) in chronic form, while mosaic attenuation, although was also frequently observed, no statistically significant differences were found between groups (p = 0.512). The most common functional pattern was restrictive (38% of patients, 73.7% with chronic HP form). Bronchoalveolar lavage lymphocytes were higher in acute and subacute forms although not reaching statistical significance (p = 0.072), with lowest CD4/CD8 ratio (p = 0.001) in acute forms. Thus, given the significant disease heterogeneity, further studies with different populations and ambient exposures are needed to achieve a better stratification of the exposure risk, to provide proper implementation of avoidance methods and a precise diagnostic and therapeutic approach.

Effects of cottonseed oil and ferrous sulfate on the performance and expression of antioxidant enzymes in broilers.

Aiming to reduce feed costs, cottonseed oil (CSO) has been used as an alternative component in diets for broilers. However, this oil contains gossypol, an antinutritional agent that impacts the use of mineral elements, inhibits glucose uptake, and has a direct inhibitory action on intestinal enzymes. Nevertheless, toxic effects of gossypol can be prevented by the addition of iron salts, such as ferrous sulfate (FS), to the diet. This work was conducted to evaluate performance and gene expression of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the intestines of 21- and 42-day-old broilers fed 0, 2, 4, or 6% concentrations of CSO, with or without FS. All CSO diets led to weight gain (WG) at 21 D. At 42 D, an increase in WG and a decrease in feed conversion (FCR) in the diets containing FS were observed. In 21-day-old birds supplemented with 4% CSO and FS, an increase in GPx gene expression was observed when compared to the 6% level. Animals (42 day old) supplemented with 6% CSO and FS presented greater expression of SOD gene when compared to 2% CSO and FS. In addition, a higher GPx expression in broilers supplemented with 6% CSO and FS compared to 6% CSO without FS was achieved. In conclusion, including CSO in the diets of broiler favors WG in animals at 21 D of age, independent of the presence or absence of FS; and including 4% CSO and FS in the diet of these animals alters the expression of the GPx gene in the intestine, so it is not necessary to add FS at 21 D. On the other hand, in 42-day-old broilers, the addition of FS is indicated, due to increases WG, decreased FCR and at the 6% CSO level without FS increase in the expression of the SOD and GPx genes.

Heterozygous TERT gene mutation associated with familial idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown cause that occurs sporadically, but it can also occur in families and so named as Familial Pulmonary Fibrosis (FPF). Some forms of FPF overlaps IPF features, namely the radiological and histological pattern of usual interstitial pneumonia (UIP). Genetic and environmental factors commonly play an important role in the pathogenesis of FPF and the most commonly identified mutations involve the telomerase complex. Here, we report a rare case of FPF in a male at the age of 44, in whom genetic testing showed heterozygous variants for the telomerase reverse transcriptase gene (TERT). Our report highlights the importance of compiling a thorough family history in younger patients identified with UIP serving as a resource for identifying the current and future genetic links to disease. Families with UIP hold a great promise in defining UIP pathogenesis, potentially suggesting targets for the development of future therapies.

Dietary L-arginine supplementation increased mammary gland vascularity of lactating sows.

The present study aimed to evaluate the mechanisms modulated by dietary arginine supplementation to sows during lactation regarding antioxidant capacity and vascularization of mammary glands. At 109 days of gestation, animals were transferred to individual farrowing crates equipped with manual feeders and automatic drinker bowls. Environmental temperature and humidity inside the farrowing rooms were registered every 15 min. At farrowing, sows were assigned in a completely randomized design to a control diet (CON) or the CON diet supplemented with 1.0% L-arginine (ARG). A total of three gilts and two sows were fed the CON diet, whereas three gilts and three sows were fed ARG diets. Sows were fed a fixed amount of 6.0 kg/day, subdivided equally in four delivery times (0700, 1000, 1300 and 1600 h) for 21 days. At weaning, sows were slaughtered and mammary tissue samples and blood from the pudendal vein were collected. Data were analyzed considering each sow as an experimental unit. Differences were considered at P<0.05. L-arginine fed sows presented lower messenger RNA (mRNA) expression for prolactin receptor (P=0.002), angiopoietin1 (P=0.03) and receptor tyrosine kinase (P=0.01); higher mRNA expression for prostaglandin synthase 1 (P=0.01); a trend of decrease for glucocorticoid receptor (P=0.06) and IGF receptor 1 (P=0.07); and a trend (P=0.05) for an increased glutathione peroxidase mRNA expression. The angiopoietin2:angiopoietin1 mRNA ratio tended to increase (P=0.07) in ARG fed sows. L-arginine fed sows had greater (P=0.04) volumetric proportion of blood vessels and a trend of enhance (P=0.07) in the number of blood vessels per mm2. These findings show that 1.0% ARG supplementation to sows activates proliferative mechanisms, may improve mammary tissues' angiogenesis and tended to increase mRNA expression of genes that encode antioxidant enzymes in mammary gland of sows.

Genotype by feed interaction for feed efficiency and growth performance traits in pigs.

A major objective of pork producers is to reduce production cost. Feeding may account for over 75% of pork production costs. Thus, selecting pigs for feed efficiency (FE) traits is a priority in pig breeding programs. While in the Americas, pigs are typically fed high-input diets, based on corn and soybean meal (CS); in Western Europe, pigs are commonly fed diets based on wheat and barley with high amounts of added protein-rich coproducts (WB), e.g., from milling and seed-oil industries. These two feeding scenarios provided a realistic setting for investigating a specific type of genotype by environment interaction; thus, we investigated the genotype by feed interaction (GxF). In the presence of a GxF, different feed compositions should be considered when selecting for FE. This study aimed to 1) verify the presence of a GxF for FE and growth performance traits in different growth phases (starter, grower, and finisher) of 3-way crossbred growing-finishing pigs fed either a CS (547 boars and 558 gilts) or WB (567 boars and 558 gilts) diet; and 2) to assess and compare the expected responses to direct selection under the 2 diets and the expected correlated responses for one diet to indirect selection under the other diet. We found that GxF did not interfere in the ranking of genotypes under both diets for growth, protein deposition, feed intake, energy intake, or feed conversion rate. Therefore, for these traits, we recommend changing the diet of growing-finishing pigs from high-input feed (i.e., CS) to feed with less valuable ingredients, as WB, to reduce production costs and the environmental impact, regardless of which diet is used in selection. We found that GxF interfered in the ranking of genotypes and caused heterogeneity of genetic variance under both diets for lipid deposition (LD), residual energy intake (REI), and residual feed intake (RFI). Thus, selecting pigs under a diet different from the diet used for growing-finishing performance could compromise the LD in all growth phases, compromise the REI and RFI during the starter phase, and severely compromise the REI during the grower phase. In particular, when pigs are required to consume a WB diet for growing-finishing performance, pigs should be selected for FE under the same diet. Breeding pigs for FE under lower-input diets should be considered, because FE traits will become more important and lower-input diets will become more widespread in the near future.

Genetic correlations between feed efficiency traits, and growth performance and carcass traits in purebred and crossbred pigs.

Selection for feed efficiency (FE) is a strategy to reduce the production costs per unit of animal product, which is one of the major objectives of current animal breeding programs. In pig breeding, selection for FE and other traits traditionally takes place based on purebred pig (PB) performance at the nucleus level, while pork production typically makes use of crossbred animals (CB). The success of this selection, therefore, depends on the genetic correlation between the performance of PB and CB (rpc) and on the genetic correlation (rg) between FE and the other traits that are currently under selection. Different traits are being used to account for FE, but the rpc has been reported only for feed conversion rate. Therefore, this study aimed 1) to estimate the rpc for growth performance, carcass, and FE traits; 2) to estimate rg between traits within PB and CB populations; and 3) to compare three different traits representing FE: feed conversion rate, residual energy intake (REI), and residual feed intake (RFI). Phenotypes of 194,445 PB animals from 23 nucleus farms, and 46,328 CB animals from three farms where research is conducted under near commercial production conditions were available for this study. From these, 22,984 PB and 8,657 CB presented records for feed intake. The PB population consisted of five sire and four dam lines, and the CB population consisted of terminal cross-progeny generated by crossing sires from one of the five PB sire lines with commercially available two-way maternal sow crosses. Estimates of rpc ranged from 0.61 to 0.71 for growth performance traits, from 0.75 to 0.82 for carcass traits, and from 0.62 to 0.67 for FE traits. Estimates of rg between growth performance, carcass, and FE traits differed within PB and CB. REI and RFI showed substantial positive rg estimates in PB (0.84) and CB (0.90) populations. The magnitudes of rpc estimates indicate that genetic progress is being realized in CB at the production level from selection on PB performance at nucleus level. However, including CB phenotypes recorded on production farms, when predicting breeding values, has the potential to increase genetic progress for these traits in CB. Given the genetic correlations with growth performance traits and the genetic correlation between the performance of PB and CB, REI is an attractive FE parameter for a breeding program.

Tissue iron quantification in chronic liver diseases using MRI shows a relationship between iron accumulation in liver, spleen, and bone marrow.

AIM: To investigate iron loading within the liver, pancreas, spleen, and bone marrow using magnetic resonance imaging (MRI) transverse relaxation rate (R2*), in patients with diffuse liver diseases; to evaluate the relationships between iron accumulation in these tissue compartments; and to assess the association between tissue iron overload and the pattern of hepatic cellular iron distribution (hepatocytes versus Kupffer cells). MATERIAL AND METHODS: Fifty-six patients with diffuse liver diseases had MRI-derived R2* values, using a multi-echo chemical-shift encoded MRI sequence, of the liver, pancreas, spleen, and vertebral bone marrow. All patients had liver biopsy samples scored for hepatic iron grading (0-4) and iron cellular distribution (within hepatocytes only or within both hepatocytes and Kupffer cells). RESULTS: Liver R2* increased with histological iron grade (RS=0.58, p<0.001) and correlated with spleen (RS=0.71, p<0.001) and bone marrow R2* (RS=0.66, p<0.001), but not with pancreatic R2* (RS=0.22, p=0.096). Splenic and bone marrow R2* values were also correlated (RS=0.72, p<0.001). Patients with iron inside Kupffer cells had the highest R2* in liver, spleen and bone marrow. CONCLUSIONS: Patients with chronic diffuse liver diseases have concomitant hepatic, splenic, and bone marrow iron loading. The highest hepatic iron scores and iron inside Kupffer cells were associated with the highest splenic and bone marrow deposits, suggesting systemic iron accumulation in the mononuclear phagocytic system.

Organizing pneumonia revisited: insights and uncertainties from a series of 67 patients.

Background: Organizing pneumonia (OP) is classified as an acute/subacute pneumonia according to the American Thoracic Society/European Respiratory Society statement (2013 update). Although its clinical presentation, radiologic and histologic features are well established, data on the relevance of potential causes, corticosteroid doses and length, or management of relapses are based on heterogeneous series of patients. Objectives: The aims of this study were to describe clinical presentation, diagnosis and treatment of OP, explore potential causes, discuss strategies for managing relapses, and analyze prognostic factors. We also discuss our findings in relation to relevant data in the literature. Methods: We performed a cross-sectional study of all patients diagnosed with OP at a tertiary referral center in northern Portugal between 2008 and 2015. Results: Sixty-seven patients were diagnosed with OP over the 7-year study period. Dyspnea and cough were the most common presenting symptoms and approximately 30% of patients were hospitalized at the time of diagnosis. Approximately half of the patients were receiving drugs described as potential causes of OP. Microorganisms were isolated in approximately one-third of patients. Other potential causes identified were hematologic disorders, neoplasms, connective tissue diseases, myelodysplastic syndromes, immunodeficiencies, radiotherapy, and bird exposure. Cryptogenic OP was diagnosed in just 16 patients (23.8%). Corticosteroids were the most common treatment and 11 patients (16.4%) experienced relapse. Conclusions: The findings for this series of patients confirm the extreme variability of the contexts in which OP can occur and suggest that rather than a distinct, homogeneous clinicopathologic entity, OP is a non-specific reaction whose outcomes are dependent on the cause. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 129-138).

Genetic parameters for semen quality and quantity traits in five pig lines.

We aimed to estimate genetic parameters for semen quality and quantity traits as well as for within-boar variation of these traits to evaluate their inclusion in breeding goals. Genetic parameters were estimated within line using a multiple-trait (4 × 4) repeatability animal model fitted for 5 pig lines, considering 4 semen traits: sperm motility (MOT), sperm progressive motility (PROMOT), log-transformed number of sperm cells per ejaculate (lnN), and total morphological abnormalities (ABN). The within-boar variation of these traits was analyzed based on a multiple-trait (2 × 2) approach for SD and average (AVG) and a single-trait analysis for CV. The average heritabilities across the 5 lines estimated by multiple-trait analysis were 0.18 ± 0.07 (MOT), 0.22 ± 0.08 (PROMOT), 0.16 ± 0.04 (lnN), and 0.20 ± 0.04 (ABN). The average genetic correlations were favorable between MOT and PROMOT (0.86 ± 0.10), between MOT and ABN (-0.66 ± 0.25), and between PROMOT and ABN (-0.65 ± 0.25). As determined by within-boar variation analysis, AVG exhibited the greatest heritabilities followed by SD and CV, respectively, for the traits MOT and ABN. For PROMOT, average SD heritability was lower than CV heritability, whereas for lnN, they were the same. The average genetic correlations between AVG and SD were favorable for MOT (-0.60 ± 0.13), PROMOT (-0.79 ± 0.14), and ABN (0.78 ± 0.17). The moderate heritabilities indicate the possibility of effective selection of boars based on semen traits. Average and SD are proposed as appropriate traits for selection regarding uniformity.

Learning curve for transbronchial lung cryobiopsy in diffuse lung disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used in the diagnosis of diffuse lung disease (DLD), but no data have yet been published on the learning curve associated with this technique. AIM: To evaluate diagnostic yield, lung tissue sample length and area, and procedure-related complications in a cohort of TBLC procedures to define the learning curve and threshold for proficiency. METHODS: Retrospective analysis of the first 100 TBLCs performed in different segments of the same lobe in patients with suspected DLD. We compared diagnostic yield, sample length and area, and complications between consecutive groups of patients. RESULTS: The overall diagnostic yield for TBLC was 82%. Median sample length was 5.4mm (IQR, 5-6) and median area was 19.5mm2 (IQR, 13.3-25). Pneumothorax was the most common complication (18%). On comparing the two groups of 50 consecutive patients, a significant difference was found for diagnostic yield (74% vs 90%; p=0.04), sample length (5.0mm [2.5-16] vs 6.0mm [4-12;] p<0.01) and area (17.5mm2 [6-42] vs 21.5mm2 [10-49]; p<0.01). Logarithm regression was applied to median diagnostic yield and sample length and area for groups of 10 consecutive patients to define the learning curve, which plateaued after approximately 70 procedures. CONCLUSIONS: Our findings suggest that proficiency in TBLC is achieved at approximately the 70th procedure; however they need to be validated in more series and cohorts.

Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle.

We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., PAPPA, PREP, FER1L6, TPR, NMNAT1, ACAD10, PCMTD1, CRH, OPKR1, NPBWR1 and NCOA2) and transcription factors (TF) (STAT1, STAT3, RELA, E2F1 and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing hormone secretion, folliculogenesis and establishment of uterine receptivity). Evidence suggests that AFC inheritance is complex and controlled by multiple loci across the genome. As several windows explaining higher proportion of the genetic variance were identified on chromosome 14, further studies investigating the interaction across haplotypes to better understand the molecular architecture behind AFC in Nellore cattle should be undertaken.

Multiple-trait genomewide mapping and gene network analysis for scrotal circumference growth curves in Brahman cattle.

Fertility traits are economically important in cattle breeding programs. Scrotal circumference (SC) measures are repeatable, easily obtained, highly heritable, and positively correlated with female fertility traits and sperm quality traits in males. A useful approach to summarize SC measures over time is using nonlinear models, which summarize specific measures of SC in a few parameters with biological interpretation. This approach facilitates the selection of bulls with larger SC and maturity index (K), that is, early maturing animals. Because SC is a sex-limited trait, identifying the underlying genomics of growth curve parameters will allow selection across both males and females. We reported the first multitrait genomewide association study (GWAS) of estimated growth curve parameters for SC data in Brahman cattle. Five widely used nonlinear models were tested to fit a total of 3,612 SC records, measured at 6, 12, 18, and 24 mo of age. The von Bertalanffy model, individually fitted for each animal, best fit this SC data. Parameter estimates SC at maturity (A) and K as well as SC at all ages were jointly analyzed in a GWAS to identify 1-Mb regions most strongly associated with each trait. Heritabilities were 0.25 for K and 0.32 for A and ranged from 0.51 to 0.72 for SC at 6 (SC6), 12 (SC12), 18 (SC18), and 24 mo of age (SC24). An overlapping window on chromosome 14 explaining around 0.8% of genetic variance for K, SC12, SC18, and SC24 was observed. The major positional candidate genes within 1 Mb upstream and downstream of this overlapping window were , , , and . Windows of 1 Mb explaining more than 0.4% of each trait on chromosomes 1, 3, 6, 7, 14, 17, 18, 24, 25, and 26 were identified. Pathways and net-work analyses were indicated through transcription factors playing a role on fertility traits: , , , , , , and . Further validation studies on larger populations or other breeds are required to validate these findings and to improve our understanding of the biology and complex genetic architecture of traits associated with scrotal growth and male fertility in cattle.