Genetic diversity analyses reveal first insights into breed-specific selection signatures within Swiss goat breeds.

We used genotype data from the caprine 50k Illumina BeadChip for the assessment of genetic diversity within and between 10 local Swiss goat breeds. Three different cluster methods allowed the goat samples to be assigned to the respective breed groups, whilst the samples of Nera Verzasca and Tessin Grey goats could not be differentiated from each other. The results of the different genetic diversity measures show that Appenzell, Toggenburg, Valais and Booted goats should be prioritized in future conservation activities. Furthermore, we examined runs of homozygosity (ROH) and compared genomic inbreeding coefficients based on ROH (FROH ) with pedigree-based inbreeding coefficients (FPED ). The linear relationship between FROH and FPED was confirmed for goats by including samples from the three main breeds (Saanen, Chamois and Toggenburg goats). FROH appears to be a suitable measure for describing levels of inbreeding in goat breeds with missing pedigree information. Finally, we derived selection signatures between the breeds. We report a total of 384 putative selection signals. The 25 most significant windows contained genes known for traits such as: coat color variation (MITF, KIT, ASIP), growth (IGF2, IGF2R, HRAS, FGFR3) and milk composition (PITX2). Several other putative genes involved in the formation of populations, which might have been selected for adaptation to the alpine environment, are highlighted. The results provide a contemporary background for the management of genetic diversity in local Swiss goat breeds.

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.

[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.

Rapid Communication: Cholesterol deficiency-associated APOB mutation impacts lipid metabolism in Holstein calves and breeding bulls.

During the last months, the number of reports on Holstein calves suffering from incurable idiopathic diarrhea dramatically increased. Affected calves showed severe hypocholesterolemia and mostly died within days up to a few months after birth. This new autosomal monogenic recessive inherited fat metabolism disorder, termed cholesterol deficiency (CD), is caused by a loss of function mutation of the bovine gene. The objective of the present study was to investigate specific components of lipid metabolism in 6 homozygous for the mutation (CDS) and 6 normal Holstein calves with different genotypes. Independent of sex, CDS had significantly lower plasma concentrations of total cholesterol (TC), free cholesterol (FC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triacylglycerides (TAG), and phospholipids (PL) compared with homozygous wild-type calves ( < 0.05). Furthermore, we studied the effect of the genotype on cholesterol metabolism in adult Holstein breeding bulls of Swissgenetics. Among a total of 254 adult males, the homozygous mutant genotype was absent, 36 bulls were heterozygous carriers (CDC), and 218 bulls were homozygous wild-type (CDF). In CDC bulls, plasma concentrations of TC, FC, HDL-C, LDL-C, VLDL-C, TAG, and PL were lower compared with CDF bulls ( < 0.05). The ratios of FC:cholesteryl esters (CE) and FC:TC were higher in CDC bulls compared with CDF bulls, whereas the ratio of CE:TC was lower in CDC bulls compared with CDF bulls ( < 0.01). In conclusion, the CD-associated mutation was shown to affect lipid metabolism in affected Holstein calves and adult breeding bulls. Besides cholesterol, the concentrations of PL, TAG, and lipoproteins also were distinctly reduced in homozygous and heterozygous carriers of the mutation. Beyond malabsorption of dietary lipids, deleterious effects of apolipoprotein B deficiency on hepatic lipid metabolism, steroid biosynthesis, and cell membrane function can be expected, which may result in unspecific symptoms of reduced fertility, growth, and health.

Clinicopathological Phenotype of Autosomal Recessive Cholesterol Deficiency in Holstein Cattle.

BACKGROUND: Cholesterol deficiency (CD), a newly identified autosomal recessive genetic defect in Holstein cattle, is associated with clinical signs of diarrhea, failure to thrive, and hypocholesterolemia. HYPOTHESIS/OBJECTIVES: The objective is to describe the clinicopathological phenotype of affected Holstein cattle homozygous for the causative apolipoprotein B gene (APOB) mutation. ANIMALS: Six Holstein cattle, 5 calves with a clinical history of chronic diarrhea, and 1 heifer with erosions in the buccal cavity and neurologic symptoms were admitted to the Clinic for Ruminants. METHODS: This case review included a full clinical examination, a complete blood count, blood chemistry, and measurements of cholesterol and triglycerides. The animals were euthanized and necropsied. A PCR-based direct gene test was applied to determine the APOB genotype. RESULTS: All 6 animals were inbred, could be traced back to the sire Maughlin Storm, and were confirmed homozygous for the APOB mutation. The clinical phenotype included poor development, underweight, and intermittent diarrhea in the calves, and neurologic signs in the heifer included hypermetria and pacing. Hypocholesterolemia and low triglycerides concentrations were present in all animals. The pathological phenotype of all animals was steatorrhea with enterocytes of the small intestine containing intracytoplasmic lipid vacuoles. The peripheral nervous system of the heifer displayed degenerative changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Suspicion of CD in Holstein cattle is based on the presence of chronic diarrhea with no evidence of primary infections. Confirmation of the associated APOB gene mutation is needed. Additionally, the heifer demonstrated primarily signs of neurologic disease providing an unexpected phenotype of CD.