Two MC1R loss-of-function alleles in cream-coloured Australian Cattle Dogs and white Huskies.

Loss-of-function variants in the MC1R gene cause recessive red or yellow coat-colour phenotypes in many species. The canine MC1R:c.916C>T (p.Arg306Ter) variant is widespread and found in a homozygous state in many uniformly yellow- or red-coloured dogs. We investigated cream-coloured Australian Cattle Dogs whose coat colour could not be explained by this variant. A genome-wide association study with 10 cream and 123 red Australian Cattle Dogs confirmed that the cream locus indeed maps to MC1R. Whole-genome sequencing of cream dogs revealed a single nucleotide variant within the MITF binding site of the canine MC1R promoter. We propose to designate the mutant alleles at MC1R:c.916C>T as e1 and at the new promoter variant as e2 . Both alleles segregate in the Australian Cattle Dog breed. When we considered both alleles in combination, we observed perfect association between the MC1R genotypes and the cream coat colour phenotype in a cohort of 10 cases and 324 control dogs. Analysis of the MC1R transcript levels in an e1 /e2 compound heterozygous dog confirmed that the transcript levels of the e2 allele were markedly reduced with respect to the e1 allele. We further report another MC1R loss-of-function allele in Alaskan and Siberian Huskies caused by a 2-bp deletion in the coding sequence, MC1R:c.816_817delCT. We propose to term this allele e3 . Huskies that carry two copies of MC1R loss-of-function alleles have a white coat colour.

[Adverse internal medicine drug effects at hospital admission]. / Unerwünschte internmedizinische Arzneimittelwirkungen bei Spitaleintritt.

Hospital admissions due to adverse drug reactions are an important concern, but there are few data concerning the specific situation in Switzerland. During one year we therefore prospectively studied all admissions to our medical department to determine the profile. 138 of 2168 patients presented a total of 150 adverse drug reactions at hospitalisation (6.4%) and among them 65% of the admissions were directly related to adverse drug reaction. Age stratification revealed that with each decade of age there was an increasing risk of adverse drug reactions and that the patients were sicker (more diagnoses), were consuming more drugs and had longer stays. The majority of adverse drug reactions were type A reactions and therefore potentially preventable. Cardio- and cerebrovascular drugs (diuretics, ACE-inhibitors, platelet aggregation inhibiting therapy) accounted for 65% of the side effects. Analysed by affected organ system, the most frequent adverse drug reactions were gastrointestinal complications followed by dehydration (contracted extracellular fluid volume) and hypo-/hyperkalaemia. Non-compliance by the patients was less frequently at the origin of the admission than iatrogenic causes related to physician errors. The patients generally did not know the reasons, details and side effects of their medical treatment. Based on our data, we estimate that the national number of drug-related hospital admissions caused by inappropriate or unnecessary treatment is 12,000-16,000, with direct annual extra costs of 70-100 million Swiss francs. Adverse drug reactions therefore represent a serious medical and financial problem. Specialised computing systems designed to reduce these events should be introduced in hospitals and ambulatory care.