A de novo germline mutation of KIT in a white-spotted Brown Swiss cow.

White-spotting coat colour phenotypes in cattle are either fixed characteristics of specific cattle breeds or occur sporadically owing to germline genetic variation of solid-coloured parents. A Brown Swiss cow showing a piebald pattern resembling colour-sidedness was referred for genetic evaluation. Both parents were normal solid-brown-coloured cattle. The cow was tested negative for the three known DNA variants in KIT, MITF and TWIST2 associated with different depigmentation phenotypes in Brown Swiss cattle. Whole-genome sequencing of the cow was performed and a heterozygous variant affecting the coding sequence of the bovine KIT gene was identified on chromosome 6. The variant is a 40 bp deletion in exon 9, NM_001166484.1:c.1390_1429del, and leads to a frameshift that is predicted to produce a novel 50 amino acid-long C-terminus replacing almost 50% of the wt KIT protein, including the functionally important intracellular tyrosine kinase domain (NP_001159956.1:p.(Asn464AlafsTer50)). Interestingly, among three available offspring, two solid-coloured daughters were genotyped as homozygous wt whereas a single son showing a slightly milder but still obvious depigmentation phenotype inherited a copy of the novel variant allele. The genetic findings provide strong evidence that the identified loss-of-function KIT variant most likely represents a de novo germline mutation that is causative owing to haploinsufficiency.

A non-coding regulatory variant in the 5'-region of the MITF gene is associated with white-spotted coat in Brown Swiss cattle.

Recently, the Swiss breeding association reported an increasing number of white-spotted cattle in the Brown Swiss breed, which is normally solid brown coloured. A total of 60 Brown Swiss cattle with variably sized white abdominal spots, facial markings and depigmented claws were collected for this study. A genome-wide association study using 40k SNP genotypes of 20 cases and 1619 controls enabled us to identify an associated genome region on chromosome 22 containing the MITF gene, encoding the melanogenesis associated transcription factor. Variants at the MITF locus have been reported before to be associated with white or white-spotted phenotypes in other species such as horses, dogs and mice. Whole-genome sequencing of a single white-spotted cow and subsequent genotyping of 172 Brown Swiss cattle revealed two significantly associated completely linked single nucleotide variants (rs722765315 and rs719139527). Both variants are located in the 5'-regulatory region of the bovine MITF gene, and comparative sequence analysis showed that the variant rs722765315, located 139 kb upstream of the transcription start site of the bovine melanocyte-specific MITF transcript, is situated in a multi-species conserved sequence element which is supposed to be regulatory important. Therefore, we hypothesize that rs722765315 represents the most likely causative variant for the white-spotting phenotype observed in Brown Swiss cattle. Presence of the mutant allele in a heterozygous or homozygous state supports a dominant mode of inheritance with incomplete penetrance and results in a variable extent of coat colour depigmentation.

[Unilateral peromelia of the left pelvic limb in a Brown Swiss calf]. / Unilaterale Peromelie der linken Beckengliedmasse bei einem Brown Swiss Kalb.

INTRODUCTION: Congenital deformities of the limbs occur sporadically in various species, but the cause is often unclear. The clinically healthy female Brown Swiss calf presented here showed a congenital peromelia of the left hind limb. The affected limb is twisted, disproportional and the bones distally of the metatarsus are missing. Karyotyping and genome sequencing did not indicate on a genetic cause of the anomaly. An infection with the Schmallenberg virus could not be ruled out. Furthermore, there was no evidence of further adverse environmental effects during pregnancy.

INTRODUCTION: Des malformations congénitales des membres, dont la cause est souvent peu claire, surviennent sporadiquement chez diverses espèces. Le veau Brown Swiss femelle présenté ici, tout en étant cliniquement sain, présentait une péromélie congénitale du postérieur gauche. Le membre concerné été en rotation interne, disproportionné et les os distalement au métatarse étaient absents. La détermination du caryotype et le séquençage de l'ensemble du génome n'ont apporté aucun élément parlant pour une cause génétique de l'anomalie. Il n'a pas été possible d'exclure une infection par le virus de ­Schmallenberg. D'autre part il n'y avait aucun élément évoquant d'autres influences environnementales néfastes durant la gestation.

A transposable element insertion in APOB causes cholesterol deficiency in Holstein cattle.

Cholesterol deficiency, a new autosomal recessive inherited genetic defect in Holstein cattle, has been recently reported to have an influence on the rearing success of calves. The affected animals show unresponsive diarrhea accompanied by hypocholesterolemia and usually die within the first weeks or months of life. Here, we show that whole genome sequencing combined with the knowledge about the pedigree and inbreeding status of a livestock population facilitates the identification of the causative mutation. We resequenced the entire genomes of an affected calf and a healthy partially inbred male carrying one copy of the critical 2.24-Mb chromosome 11 segment in its ancestral state and one copy of the same segment with the cholesterol deficiency mutation. We detected a single structural variant, homozygous in the affected case and heterozygous in the non-affected carrier male. The genetic makeup of this key animal provides extremely strong support for the causality of this mutation. The mutation represents a 1.3kb insertion of a transposable LTR element (ERV2-1) in the coding sequence of the APOB gene, which leads to truncated transcripts and aberrant splicing. This finding was further supported by RNA sequencing of the liver transcriptome of an affected calf. The encoded apolipoprotein B is an essential apolipoprotein on chylomicrons and low-density lipoproteins, and therefore, the mutation represents a loss of function mutation similar to autosomal recessive inherited familial hypobetalipoproteinemia-1 (FHBL1) in humans. Our findings provide a direct gene test to improve selection against this deleterious mutation in Holstein cattle.

Injury Patterns among Elite Football Players: A Media-based Analysis over 6 Seasons with Emphasis on Playing Position.

The study objective was to describe the types, localizations and severity of injuries among first division Bundesliga football players, and to study the effect of playing position on match and training injury incidence and severity, based on information from the public media. Exposure and injuries data from 1 448 players over 6 consecutive seasons were collected from a media-based register. In total, 3 358 injuries were documented. The incidence rate for match and training injuries was 11.5 per 1 000 match-hours (95% confidence interval [CI]: 10.9-12.2), and 61.4 per 100 player-seasons (95% CI: 58.8-64.1), respectively. Strains (30.3%) and sprains (16.7%) were the major injury types, with the latter causing significantly longer lay-off times than the former. Significant differences between the playing positions were found regarding injury incidence and injury burden (lay-off time per incidence-rate), with wing-defenders sustaining significantly lower incidence-rates of groin injuries compared to forwards (rate ratio: 0.43, 95% CI: 0.17-0.96). Wing-midfielders had the highest incidence-rate and injury burden from match injuries, whereas central-defenders sustained the highest incidence-rate and injury burden from training injuries. There were also significant differences in match availability due to an injury across the playing positions, with midfielders sustaining the highest unavailability rates from a match and training injury. Injury-risk and patterns seem to vary substantially between different playing positions. Identifying positional differences in injury-risk may be of major importance to medical practitioners when considering preventive measures.

In situ determination of Clostridium endospore membrane fluidity during pressure-assisted thermal processing in combination with nisin or reutericyclin.

This study determined the membrane fluidity of clostridial endospores during treatment with heat and pressure with nisin or reutericyclin. Heating (90°C) reduced laurdan (6-dodecanoyl-2-dimethylaminonaphthalene) general polarization, corresponding to membrane fluidization. Pressure (200 MPa) stabilized membrane order. Reutericyclin and nisin exhibit divergent effects on heat- and pressure-induced spore inactivation and membrane fluidity.

[Grey, curly and short-haired Swiss Holstein cattle show genetic traces of the Simmental breed]. / Graue, kraus- und kurzhaarige Schweizer Holstein Rinder weisen genetische ­Spuren der Rasse Simmental auf.

INTRODUCTION: Occasionally black-and-white spotted calves appear in Switzerland, which show a special fur only in the pigmented area. Otherwise these animals are normally developed. The white hairs are normal, but they appear relatively long and smooth, because the pigmented hairs are curly and thus appear shortened. In addition, the affected animals show a variable intensity of coat colour in the pigmented area. At birth affected calves often appear black, whereas older cattle show bright colours from reddish brown to grey. This is associated with a variable hair loss that increases during growth and is limited to the pigmented area of the coat. In adult cattle the coloured hairs appear rather smooth, but they are considerably shorter. This phenomenon of pigmentation-associated hypotrichosis was previously described internationally in various beef cattle populations. The affected cattle are often solid black and show only small white spots. Therefore, the loss of hair at the pigmented fur and most visibly at the pigmented tail is called rat-tail syndrome. Another name used is also crossbreeding-related congenital hypotrichosis. Molecular genetic investigations showed that the affected animals are heterozygous carriers for two variants in two different genes associated with pigmentation. The same genotype constellation was found in the 33 similarly affected cattle from Switzerland presented here. On one hand, they each carry a copy of the MC1R gene gain-of-function variant causing dominant black, as well as a copy of the recessively inherited red factor loss-of-function variant in the MC1R gene. On the other hand, all cases are heterozygous carriers for a variant in the PMEL gene that is associated with a semi-dominantly inherited form of colour dilution (dun or silver) in Simmental, Hereford and Highland Cattle. The introgression of Holstein cattle into the Original Simmental breed, which has been practised for decades, explains the occasional occurrence of this phenomenon in Swiss cattle breeding.

INTRODUCTION: En Suisse, on peut parfois observer des veaux tachetés noirs et blancs présentant un pelage spécial uniquement dans la zone pigmentée des poils. Ces animaux sont normalement développés; les poils blancs sont normaux mais semblent relativement longs et lisses, alors que les poils pigmentés sont bouclés et raccourcis. En outre, les animaux atteints présentent une intensité variable de la couleur du pelage dans la zone pigmentée. À la naissance, ces veaux apparaissent souvent noirs, alors qu'en grandissant ils présentent une couleur plus claire allant du brun rougeâtre au gris. Chez les bovins adultes, les poils colorés semblent plutôt lisses mais sont nettement raccourcis. Ceci est associé à une diminution de la pilosité variable augmentant pendant la croissance et se limitant à la zone pigmentée du pelage. Ce phénomène d'hypotrichose associée à la pigmentation a déjà été décrit au niveau international dans diverses races à viande bovines. Ces bovins sont souvent d'un noir uniforme et ne présentent que de petites taches blanches. En raison de la perte de poils dans le pelage pigmenté et plus visiblement au niveau de la queue pigmentée, on appelle ce syndrome syndrome de la queue de rat (rat-tail syndrom), également appelé hypotrichose congénitale liée au croisement. Les études de génétique moléculaire ont montré que les animaux affectés sont porteurs hétérozygotes de deux variantes de deux gènes différents associés à la pigmentation. La même constellation génotypique a été retrouvée chez les 33 bovins suisses présentés ici. D'une part, ces derniers portent chacun une copie de la variante du gène dominant MC1R causant le noir, ainsi qu'une copie de la variante récessive du facteur rouge dans le gène MC1R. D'autre part, tous les cas sont porteurs hétérozygotes d'une variante du gène PMEL associée à une forme de dilution de couleur semi-dominante héréditaire (dun ou argent) chez les races Simmental, Hereford et Highland Cattle. Le croisement des bovins Holstein avec la race Simmental originale, pratiquée depuis des décennies, explique la présence occasionnelle de ce phénomène dans l'élevage bovin suisse.

The management of juxtahepatic venous injuries without an atriocaval shunt: preliminary clinical observations.

Juxtahepatic venous injuries are usually fatal. The optimal method of dealing with these injuries remains controversial, but most experience has been with the insertion of an atriocaval shunt. However, the mortality rate with atriocaval shunting remains prohibitively high (60% to 100%). The experience at the Bellevue Hospital Trauma and Shock Unit during a 9-year period revealed a 50% mortality rate in four consecutive patients who underwent atriocaval shunting. As such, a different approach was used in the following five patients, all of whom survived. One additional patient died in the operating room before any definitive repair could be undertaken. Four steps are considered essential to the successful management of these patients: (1) compression of the injury site until adequate resuscitation has been achieved; (2) early recognition that a juxtahepatic venous injury exists, as indicated by failure of the Pringle maneuver to adequately arrest hemorrhage; (3) prolonged portal triad occlusion with hepatocyte protection by means of large doses of steroids and topical hypothermia (portal triad occlusion time in the nonshunted group ranged from 20 to 64 minutes with a mean occlusion time of 46 minutes; although a transient rise in liver function test results seemed to correlate with the length of ischemia time, neither hepatic dysfunction nor hepatic necrosis occurred; and (4) extensive finger fracture of the liver to the site of vascular injury for primary repair or ligation; the extent of the finger fracture varied from 15 to 30 cm in length and from 5 to 15 cm in depth. The successful results achieved in five consecutive patients who sustained juxtahepatic venous injuries treated without a shunt serve as a basis for recommending this operative approach.

Open and percutaneous paracentesis and lavage for abdominal trauma: a randomized prospective study.

To compare the accuracy and safety of open abdominal paracentesis and lavage vs percutaneous paracentesis and lavage, 210 consecutive patients were prospectively randomized into two groups of 105 each. There were no false-negative diagnoses in either group. The accuracy rate for the open method was 98.1%, and 91.4% for the percutaneous method. Six major complications were encountered with the percutaneous method, for a complication rate of 5.7% compared with no major complications with the open method. The results suggest that the open technique is superior to the percutaneous method.

The current status of nonoperative management of adult blunt hepatic injuries.

This review of 14 recent publications encompassing 495 patients highlights the current role of the nonoperative management of adult blunt hepatic injuries. When careful inclusion criteria were met, the most important of which is hemodynamic stability, a 94% success rate was achieved, clearly attesting to the safety and efficacy of this approach. A 0% liver-related mortality in these 495 patients was achieved, and there were no documented missed enteric injuries. Delayed hemorrhage that led to laparotomy occurred in 2.8% of patients. The mean length of hospital stay was 13 days, and the mean transfusion requirement was 1.9 units of blood per patient. Computed axial tomography scanning was essential and played an integral role in delineating the extent of the injury, identifying other intra-abdominal injuries that would mandate immediate laparotomy, and following the progress of injury resolution. Overall, 34% of blunt liver injuries were managed nonoperatively. As of 1993, however, available data confirms that 51% of adult reported blunt hepatic injuries have been treated nonoperatively. Rigid adherence to the described guidelines may allow the majority of blunt hepatic injuries to be treated nonoperatively. It should be stressed, however, that this method of patient management should only be undertaken at institutions where the appropriate resources necessary to deal with this patient population are readily available.