Genetic and genomic evaluation of age at first calving in Italian Holsteins.

Age at first calving (AFC) represents the nonproductive period of ∼2 yr in Holstein cows, and thus, it has a relevant effect on the cost of rearing replacements in the dairy herd. In the present study, we aimed to evaluate genetic and genomic aspects of AFC in the Italian Holstein population. Data of 4,206,218 heifers with first calving between 1996 and 2020 were used. Age at first calving averaged 26.09 ± 3.07 mo and decreased across years. Heritability was estimated using a linear animal model which included the fixed effects of herd-year-season of birth and classes of gestation length, and the random animal additive genetic effect fitted to a pedigree-based relationship matrix. The EBV and genomically EBV (GEBV) were obtained, and they were standardized to mean 100 and standard deviation 5, where animals above the mean are those contributing to reduce AFC. Heritability estimates of AFC ranged from 0.031 to 0.045. The trend of sires' GEBV was favorable and indicated a reduced AFC across years. Approximate genetic correlations between GEBV of AFC and GEBV of other economically important traits were calculated on a subset of genotyped females born after 2015. Moderate favorable associations of AFC with production traits (0.39-0.51), udder depth (0.40), interval from first to last insemination in heifer (-0.43), and longevity (0.34) were assessed. Overall, the greatest lifetime productive performances and most favorable days open in first lactation were observed when heifers calved at 22 to 23 mo. In contrast, progeny of sires with GEBV of AFC above the mean yielded more milk, fat, and protein in first lactation, and had shorter days open than progeny of sires with GEBV of AFC below the mean. Results suggested that breeding strategies to improve AFC should be pursued, also considering genetic correlations between AFC and traits which are already part of the Italian Holstein breeding objective. The inclusion of AFC in an aggregate index is expected to contribute to enhance farm income.

Genetic correlations between fertility traits and milk composition and fatty acids in Holstein-Friesian, Brown Swiss, and Simmental cattle using recursive models.

This study aimed to investigate the genetic and putative causal relationships between fertility traits [i.e., days open (DO) and calving rate (CR)] and milk quality, composition, and fatty acid contents (milk composition traits) in Holstein-Friesian, Brown Swiss, and Simmental cattle, using recursive models within a Bayesian framework. Trivariate animal models were run, each including one fertility trait, one milk composition trait, and, in all models, milk yield. The DO and CR data were merged with the test days closest to the insemination date for milk composition traits. After editing, 16,468 to 23,424 records for Holstein-Friesian, 23,424 to 46,660 for Brown Swiss, and 26,105 to 35,574 for Simmental were available for the analyses. Recursive animal models were applied to investigate the possible causal influences of milk composition traits on fertility and the genetic relationships among these traits. The results suggested a potential cause-and-effect relationship between milk composition traits and fertility traits, with the first trait influencing the latter. We also found greater recursive effects of milk composition traits on DO than on CR, the latter with some putative differences among breeds in terms of sensitivity. For instance, the putative causal effects of somatic cell score on CR (on the observed scale, %) varied from -0.96 to -1.39%, depending on the breed. Concerning fatty acids, we found relevant putative effects of C18:0 on CR, with estimates varying from -7.8 to -9.9%. Protein and casein percentages, and short-chain fatty acid showed larger recursive effects on CR, whereas fat, protein, and casein percentages, C16:0, C18:0, and long-chain fatty acid had larger effects on DO. The results obtained suggested that these milk traits could be considered as effective indicators of the effects of animal metabolic and physiological status on fertility.

Genetic parameters for fertility traits assessed in herds divergent in milk energy output in Holstein-Friesian, Brown Swiss, and Simmental cattle.

In this study, we aimed to investigate differences in the genetics of fertility traits (heritability of traits and correlations between traits in divergent environments) in dairy cows of different production levels defined on the basis of the herd-average daily milk energy output (herd-dMEO). Data were obtained from Holstein-Friesian (n = 37,359 for fertility traits, 381,334 for dMEO), Brown Swiss (n = 79,638 for fertility traits, 665,697 for dMEO), and Simmental cows (n = 63,048 for fertility traits, 448,445 for dMEO) reared in northeastern Italy. Fertility traits under study were interval from calving to first service, interval from first service to conception, days open, calving interval, calving rate, and nonreturn rate at d 56. We classified herds into low and high productivity based on the herd-average dMEO (inferred using mixed effects models). We estimated genetic parameters using Bayesian bivariate animal models, where expressions of a phenotype in the low and high dMEO herds were taken as being different-albeit correlated-traits. Fertility traits were more favorable in Simmental than in Holstein-Friesian cows, whereas for all traits, Holstein-Friesian had the highest estimates of intraherd heritability [ranging from 0.021 (0.006-0.038) to 0.126 (0.10-0.15)] and Simmental the lowest [ranging from 0.008 (0.001-0.017) to 0.101 (0.08-0.12)]. The genetic correlations between fertility traits and dMEO were moderate and unfavorable, ranging, in absolute values, from 0.527 (0.37-0.68) to 0.619 (0.50-0.73) in Holstein-Friesian; from 0.339 (0.20-0.47) to 0.556 (0.45-0.66) in Brown Swiss; and from 0.340 (0.10-0.60) to 0.475 (0.33-0.61) in Simmental cattle. The only exception was the nonreturn rate at d 56, which had weak genetic correlations with dMEO in all 3 breeds. The herd correlations between fertility and dMEO tended to be modest and favorable and the residual correlations modest and variable. The heritability of fertility traits tended to be greater in the low dMEO than in the high dMEO herds in the case of the Holstein-Friesians, but not in the case of the Brown Swiss or Simmentals. The additive genetic correlations between fertility traits in the low and high dMEO herds were always lower than 1 [0.329 (-0.17 to 0.85) to 0.934 (0.86 to 0.99)] for all traits considered in all breeds. The correlation was particularly low for the threshold characters and the interval from first service to conception in Holstein-Friesian, suggesting that the relative performances of genotypes vary significantly between herds of different dMEO levels. Although there was large variability in the estimates, results might support making separate genetic evaluations of fertility in the different herd production groups. Our results also indicate that Simmental, a dual-purpose breed, has higher fertility and lower environmental sensitivity than Holstein-Friesian, with Brown Swiss being intermediate.

Invited review: Determination of large-scale individual dry matter intake phenotypes in dairy cattle.

Feed efficiency has been widely studied in many areas of dairy science and is currently seeing renewed interest in the field of breeding and genetics. A critical part of determining how efficiently an animal utilizes feed is accurately measuring individual dry matter (DM) intake. Currently, multiple methods are used to measure feed intake or determine the DM content of that feed, resulting in different levels of accuracy of measurement. Furthermore, the scale at which data need to be collected for use in genetic analyses makes some methodologies impractical. This systematic review aims to provide an overview of the current methodologies used to measure both feed intake in ruminants and DM content of feedstuffs, current methods to predict individual DM intake, and applications of large-scale intake measurements. Overall, advances in milk spectral data analysis present a promising method of estimating individual DM intake on a herd scale with further validation of prediction models. Although measurements of individual feed intake rely on the same underlying principle, the methods selected are largely dictated by the costs of capital, labor, and necessary analyses. Finally, DM methodologies were synthesized into a comprehensive protocol for use in a variety of feedstuffs.

Alternative somatic cell count traits exploitable in genetic selection for mastitis resistance in Italian Holsteins.

The aim of the present study was to characterize alternative somatic cell count (SCC) traits that could be exploited in genetic selection for mastitis resistance. Data were from 66,407 first-parity Holsteins in 404 herds. Novel SCC traits included average somatic cell score (SCS, log-transformation of SCC) in early lactation (SCS_150), standard deviation of SCS of the entire lactation (SCS_SD), the presence of at least one test-day (TD) SCC >400,000 cells/mL in the lactation, and the ratio of number of TD SCC >400,000 cells/mL to total number of TD in the lactation. Novel traits and lactation-mean SCS (SCS_LM) were analyzed using linear mixed or logistic regression models, including month of calving, year of calving, number of TD, and milk yield as fixed effects, and herd and residual as random terms. A multitrait linear animal model was applied to a random subset of 152 herds (n = 22,695 cows) to assess heritability of and genetic correlations between SCC traits. Alternative SCC traits were affected by the environmental factors included in the model; in particular, results suggested a seasonal effect and a tendency toward an improvement of the udder health status in the last years. Association was also found between novel SCC traits and milk production. Alternative SCC traits exhibited coefficients of additive genetic variation that were similar to or larger than that of traditional SCS_LM. Heritability of novel SCC traits was smaller than heritability of SCS_LM (0.126 ± 0.014), ranging from 0.044 ± 0.008 (SCS_SD) to 0.087 ± 0.010 (SCS_150). Genetic correlations between SCC traits ranged from 0.217 ± 0.096 (SCS_150 and SCS_SD) to 0.969 ± 0.010 (SCS_LM and SCS_150). Alternative SCC traits exhibited additive genetic variation that is potentially exploitable in breeding programs of Italian Holstein population to improve resistance to mastitis.

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. INTRODUCTION: The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. METHODS: This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. RESULTS: Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. CONCLUSIONS: This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.

Genetic and nongenetic variation of heifer fertility in Italian Holstein cattle.

Excellent fertility performance is important to maximize farmers' profit and to reduce the number of culled animals. Although female fertility of adult cows has been included in Italian Holstein breeding objectives since 2009, little has been done to quantify genetic variation of heifer fertility characteristics so far. The aim of the present study was to estimate genetic parameters of 4 fertility traits in nulliparous Italian Holstein heifers and to develop an aggregate selection index to improve heifer fertility. Data were retrieved from the national fertility database and included information on insemination, calving, and pregnancy diagnosis dates. The investigated phenotypes (mean ± standard deviation) were age at first insemination (AFI, mo; 17.25 ± 2.89), nonreturn rate at 56 d from the first insemination (NRR56, binary; 0.78 ± 0.41), conception rate at first insemination (CR, binary; 0.61 ± 0.49), and interval from first to last insemination (IFL, d; 26.09 ± 51.85). Genetic parameters were estimated using a 4-trait animal model that included the following fixed effects: herd-year of birth and month of birth for AFI, and herd-year-season of birth and month-year of insemination for IFL, NRR56, and CR; the animal additive genetic effect (fitted to the pedigree-based relationship matrix) was considered as a random term. An aggregate index was developed from the estimated additive genetic (co)variance matrix by considering CR as the breeding goal and AFI, NRR56, and IFL as selection criteria. Heritability estimates from average covariance matrices ranged from 0.012 (CR) to 0.015 (IFL), with the exception of AFI (0.071). Conception rate at first insemination was strongly correlated with both IFL (-0.730) and NRR56 (0.668), and weakly to AFI (-0.065), and the relative emphasis placed on each selection criteria in the aggregate index was 10%, 47%, and 43% for AFI, IFL, and NRR56, respectively. The results of the present study suggest that heifer fertility should be considered as an additional trait in the breeding objectives of Italian Holstein.

Hierarchical structure of the Sicilian goats revealed by Bayesian analyses of microsatellite information.

Genetic structure and relationship amongst the main goat populations in Sicily (Girgentana, Derivata di Siria, Maltese and Messinese) were analysed using information from 19 microsatellite markers genotyped on 173 individuals. A posterior Bayesian approach implemented in the program STRUCTURE revealed a hierarchical structure with two clusters at the first level (Girgentana vs. Messinese, Derivata di Siria and Maltese), explaining 4.8% of variation (amovaФ(ST) estimate). Seven clusters nested within these first two clusters (further differentiations of Girgentana, Derivata di Siria and Maltese), explaining 8.5% of variation (amovaФ(SC) estimate). The analyses and methods applied in this study indicate their power to detect subtle population structure.

Absence of severe recurrent infections in glycogen storage disease type Ib with neutropenia and neutrophil dysfunction.

We describe a 10-year-old boy with glycogen storage disease type Ib (GSD Ib) with neutropenia and neutrophil dysfunction who never suffered from severe recurrent infections. Lymphocyte subpopulations and assay of intracellular cytokines (IL-2, IL-4 and IFN-gamma) showed a pattern of lymphocyte activation suggesting a shift of T(H)1/T(H)2 balance towards a T(H)1 response. This is the first report of GSD Ib without severe recurrent infections in spite of neutropenia and neutrophil dysfunction.

Parameters for milk somatic cell score and relationships with production traits in primiparous dairy sheep.

A total of 13,066 first-lactation test-day records of 2,277 Valle del Belice ewes from 17 flocks were used to estimate genetic parameters for somatic cell scores (SCS) and milk production traits, using a repeatability test-day animal model. Heritability estimates were low and ranged from 0.09 to 0.14 for milk, fat, and protein yields, and contents. For SCS, the heritability of 0.14 was relatively high. The repeatabilities were moderate and ranged from 0.29 to 0.47 for milk production traits. The repeatability for SCS was 0.36. Flock-test-day explained a large proportion of the variation for milk production traits, but it did not have a big effect on SCS. The genetic correlations of fat and protein yields with fat and protein percentages were positive and high, indicating a strong association between these traits. The genetic correlations of milk production traits with SCS were positive and ranged from 0.16 to 0.31. The results showed that SCS is a heritable trait in Valle del Belice sheep and that single-trait selection for increased milk production will also increase SCS.

Effect of D-ribose on purine synthesis and neurological symptoms in a patient with adenylosuccinase deficiency.

Oral supplementation of 10 mmol/kg/day of D-ribose to a patient with an inherited deficit of adenylosuccinase, severe psychomotor retardation, and epilepsy caused a marked increase in plasma concentration and urinary excretion of urate, while minor changes in succinylpurine levels were observed. D-Ribose administration was accompanied by a slight improvement of behaviour and a progressive reduction of seizure frequency, which increased dramatically upon two attempts to withdraw the drug. Substitution of D-ribose with an equivalent amount of D-glucose did not result in an increase of seizure frequency.

Child with manifestations of dermotrichic syndrome and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome.

We report on a boy with short stature, mental retardation, seizures, follicular ichthyosis, generalized alopecia, hypohydrosis, enamel dysplasia, photophobia, congenital aganglionic megacolon, inguinal hernia, vertebral, renal and other anomalies, and a normal chromosome constitution. The clinical findings include all the features that dermotrichic and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia, recurrent respiratory infections, etc.), those that are present only in dermotrichic syndrome (nail anomalies, hypohydrosis, megacolon, vertebral defects, etc.) and additional ones (enamel dysplasia, renal anomalies, inguinal hernia, etc.). Two maternal uncles were referred as being affected by alopecia and ichthyosis suggesting X-linked recessive transmission. Various hypotheses concerning the relationship between the 2 syndromes and the present case are discussed.

Low serum tryptophan to large neutral amino acids ratio in idiopathic infantile autism.

The serum tryptophan to large neutral amino acids ratio (Try/LNAA) is considered a reliable marker of tryptophan availability for brain serotonin synthesis. A dysfunction of brain serotonergic activity has been postulated to exist in autistic disorder and supported by recent studies. On this basis, we determined the serum amino acids levels in 40 children with idiopathic infantile autism as well as in 46 control children. A significantly lower serum Try/LNAA ratio was observed in the autistic subjects compared to the normal controls. In 14 autistic children (35%) this ratio was 2 SD below the mean value obtained in the control group. These results suggest that a low brain tryptophan availability due to a low serum Try/LNAA ratio could be one of the possible mechanisms involved in the alteration of serotonergic function in autism.

Fatty acid profile of oesophageal mucosa in children with gastro-oesophageal reflux disease.

BACKGROUND: Polyunsaturated fatty acids, as precursors of eicosanoids, are involved in the pathogenesis of oesophageal mucosal damage and healing. AIMS: To evaluate a possible role of polyunsaturated fatty acids in the pathogenesis of gastro-oesophageal reflux, we assayed fatty acids profile of oesophageal mucosal specimens obtained by endoscopy in children without oesophageal disease and children affected by gastro-oesophageal reflux disease. PATIENTS: Eighteen children with normal 24-h oesophageal pH monitoring (GOR- group) and 18 children with gastro-oesophageal reflux disease (GOR+ group, eight with oesophagitis and 10 without), were included in the study. METHODS: Fatty acids were extracted from oesophageal mucosal specimens obtained by endoscopy and assayed by gas chromatography. RESULTS: In the GOR+ group we observed an increased percentage of mucosal polyunsaturated fatty acids, mainly arachidonic and docosohexaenoic acids (p<0.01), without differences between groups with and without oesophagitis. Significant positive correlation was found between reflux index and docosahexaenoic acid (r=0.805; p<0.001). CONCLUSIONS: The results obtained show that the current methods are able to reveal changes between normal and pathological mucosa that could be relevant in the pathogenesis of gastro-oesophageal reflux disease.

The effect of brain radiotherapy on the P3 component of ERP's.

Nine patients with lung cancer without brain metastasis were studied pre and post brain prophylactic radiotherapy (30 Gy) to verify the effect of radiation on the cognitive processes. The P3 component of event-related potentials was used in this study. The latencies pre and post-radiation were compared and a significant delay (p less than 0.01) was detected in patients after treatment. These results suggest that brain radiotherapy may produce a cognitive impairment, as reported by many Authors.

Brain-stem auditory evoked potentials in supratentorial brain tumors.

A group of 42 adult patients with supratentorial brain tumors were studied with computed tomography (CT or/and NMR) and brain-stem evoked potentials (BAEPs). 12 patients had meningiomas and 30 had malignant tumors (gliomas and metastases). The latencies of wave V and of the interpeak latency I-III, III-V and I-V were evaluated both on the lesion side and the opposite side. In meningiomas mean latencies did not show significant differences from normal, while mean latencies in malignant tumors were significantly prolonged, except for the I-III interpeak latency. The results of this study demonstrate that BAEPs may be altered by supratentorial brain tumors. This examination appears to be useful in the monitoring of these lesions after treatment.

Taurine deficiency in thalassemia major-induced osteoporosis treated with neridronate.

The aetiology of thalassemia major-induced osteoporosis is multifactorial. Up to now, bisphosphonates seem to be a promising therapy. Taurine is found in a high concentration in bone cells enhancing bone tissue formation and inhibiting bone loss. Recently we found a decrease taurine plasma level in children affected by osteogenesis imperfecta during neridronate (amino-bisphosphonate) therapy suggesting a possible interaction between pharmacological effect of this drug and taurine availability. On the basis of these results, we performed plasma and urine amino acid (AA) analysis in thalassemia major-induced osteoporosis before and after 12 months of neridronate treatment. Twelve patients, five males and seven females, aged from 20 to 29 years following a hypertransfusion treatment protocol were enrolled in the study. Patients were treated with neridronate infusion every one month (30 mg in 100ml of saline). Plasma and urine specimens for AA analysis, bone mineral density, bone mineral content and vertebral project area were examined at baseline (T0) and after 12 months of treatment (T12). A significant decrease was observed for plasma level and urinary excretion of taurine (T0 vs. T12=p<0.01) whereas bone mineral content and vertebral projection area showed a statistical significant increase (T0 vs. T12=p<0.05). These results and other experimental researches warrant further studies examining the long-term effect of taurine supplementation in association with neridronate treatment.