Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers.

OBJECTIVE: Glucocerebrosidase (GBA) gene mutations represent a strong risk factor for Parkinson disease (PD). PD penetrance in GBA mutation carriers, which represents a key issue for genetic counseling, especially for relatives of patients with Gaucher disease (GD), is unknown. Our objective was to estimate PD penetrance in a familial study of GBA mutation carriers. METHODS: Probands with familial PD were recruited through the French Parkinson Disease Genetic Study Group. All GBA exons were sequenced in probands and their relatives. To estimate the age-specific cumulative PD risk (i.e., penetrance) in GBA mutation carriers, we used the proband's phenotype exclusion likelihood method and corrected for selection of familial cases by considering the status of one affected relative per family as unknown. RESULTS: Of 525 probands with familial PD, 24 (4.6%) were GBA mutation carriers. Of their 256 relatives, 43 (16.8%) had PD and 26 of 32 affected relatives tested for GBA mutations were mutation carriers; 213 relatives did not have PD and 31 of 71 of unaffected relatives tested for GBA mutations were mutation carriers. Under a dominant model, penetrance was estimated as 7.6%, 13.7%, 21.4%, and 29.7% at 50, 60, 70, and 80 years, respectively. There was no significant difference in penetrance at 70 years between N370S carriers, L444P carriers, and carriers of rarer mutations. CONCLUSION: The relatively high penetrance estimate in GBA carriers obtained in this study should lead to consideration of GBA as a dominant causal gene with reduced penetrance and should be taken into account for genetic counseling in relatives of patients with GD and patients with GBA-associated PD.

Milk yield, age at first calving, and the risk of BSE: an analysis at the farm level in France.

The epidemic of bovine spongiform encephalopathy (BSE) in France, as in the UK, has affected dairy cattle much more than beef cattle. However, the intensification of dairy herd management as a risk factor for BSE has not to date been analyzed. For this purpose, two databases were merged: the French Milk Records database, and the French BSE database, which can be considered as being devoid of notification bias since July 2001, when systematic tests were implemented. Only pure Holstein herds were considered, which represent the vast majority of total and BSE-affected dairy herds in France. A case-control study was designed so that 20 control herds were matched to each case herd according to the location of the farm and the year of birth of the index case. Three thousand and forty five farms were included, among which 145 with a BSE case notified between July 2001 and July 2003, and 2900 controls. With respect to the risk of BSE, odds ratios for each class of milk yield and age at first calving were estimated by using conditional logistic regression models with appropriate adjustments to herd size. The two main results were the following: firstly, whereas most Holstein herds, with average production between 7000 and 10,000kg, had nearly the same BSE risk, a small category of very intensive herds, with annual milk yields above 10,000kg, were significantly more at risk than the other herds. Secondly, a very early first calving (under 26 months of age) was found to be at risk for BSE as compared to other categories, independently of the milk yield. These results are discussed in the light of the known age-dependent susceptibility to BSE.

Three methods to validate the estimation of genetic trend for dairy cattle.

Three methods are proposed to validate the estimation of genetic trend for dairy cattle. With the first method, official evaluations, which are generally derived from a repeatability animal model applied to lactation records from several parities, are compared with evaluations based only on first parity to determine whether estimates of genetic trend are similar. With the second method, daughter yield deviations are analyzed within sire by calving year to determine whether these deviations remain stable over time. With the third method, variations of successive official evaluations are analyzed by regression to determine any systematic trend associated with information from additional daughters. Access to raw data is needed for the first two methods, but only published evaluations are needed for the third method. The three methods were applied to French Holstein evaluations calculated with 1990 and 1993 animal models and validated estimates of genetic trend based on information from the 1993 animal model.

Effects of feeding practices on milk fat concentration for dairy cows.

Thirty-seven dairy farms, using high producing (7500 kg/yr per cow on average) Montbéliarde cows that were fed hay-based rations, were included in a detailed survey involving the structure of the farm and the herd, the quality of forage, the feeding practices in winter and summer, and genetic characteristics of the cows (breeding values and herd effects). These data were used to analyze variation in milk fat concentration among farms, particularly variation linked to environmental factors, as assessed by the herd effect. When farms were ranked according to herd effect of fat concentration, farms with the highest herd effects fed concentrate to cows in rolled form, distributed forage before or with the concentrate, and provided hay in the trough in summer. The effects of such practices on digestive phenomena in the rumen are discussed. This study supported the use of herd effects to identify factors related to variation in dairy cow performance.