A new scoring system in cancer genetics: application to criteria for BRCA1 and BRCA2 mutation screening.

Background: In hereditary forms of cancer due to mutations of genes such as BRCA1 and BRCA2, methods have been proposed to predict the presence of a mutation in a family.

Methods: Relying on carriage probability computation is the most predictive, but scores are a good proxy and avoid using computer software. An empirical method, the Manchester scoring system, has been elaborated for BRCA1 and BRCA2 mutation identification.

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.

[A new scoring system for the diagnosis of BRCA1/2 associated breast-ovarian cancer predisposition].

Criteria have been proposed for genetic testing of breast and ovarian cancer susceptibility genes BRCA1 and BRCA2. Using simulations, this study evaluates the efficiency (sensitivity, positive predictive value [PPV] and specificity) of the various criteria used in France. The efficiency of the criteria published in 1998, which are largely used, is not optimal.

Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.

Context: Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome.

Objective: To estimate the age-specific cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes.

Design, Setting, And Participants: Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6) were analyzed.

Estimating penetrance from multiple case families with predisposing mutations: extension of the 'genotype-restricted likelihood' (GRL) method.

Some diseases are due to germline mutations in predisposing genes, such as cancer family syndromes. Precise estimation of the age-specific cumulative risk (penetrance) for mutation carriers is essential for defining prevention strategies. The genotype-restricted likelihood (GRL) method is aimed at estimating penetrance from multiple case families with such a mutation.

TTR familial amyloid polyneuropathy: does a mitochondrial polymorphism entirely explain the parent-of-origin difference in penetrance?

The Val30Met transthyretin familial amyloid polyneuropathy (TTR-V30M-FAP) is the most frequent familial amyloidosis, with autosomal dominant transmission. This severe disease shows important differences in age of onset and penetrance. Recently, a difference in penetrance according to the gender of the transmitting parent was elicited in different geographic areas with a higher penetrance in case of maternal transmission of the trait.

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.

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.

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.