Demographic genetics of the endangered Amiata donkey breed

The demogenetic structure of the Amiata donkey, an endangered breed from Central Italy, was investigated using information from pedigrees. Genealogical data of 602 donkeys reared in Tuscany were recorded in a database and analysed by the computer package ENDOG. Population size increased from 89 subjects in 1995 to 503 (129 males and 374 females) in 2005. Animals were distributed among 152 herds, but the effective number of herds was 21, suggesting that a small number of herds provided stallions for the entire breed. The maximum number of traced generation was 4, the mean maximum generation was 1.14, the mean com- plete generation was 0.53, and the mean equivalent generation was 0.78. The average relatedness coeffi- cient (AR) in the 503 alive animals was 0.94% while the mean F was 0.29% so the effective population size was 172.41. Among 24 animals with a 4-generation history, 3 (12.5%) were 25% inbred. Although the incompleteness of genealogical information did not permit accurate inference of the current values of popu- lation genetic parameters, the present work represents a first step towards an efficient management of the breed

Haplotype association analysis of meat quality traits at the bovine PRKAG3 locus

The current study presents the results of a preliminary haplotype association analysis at the bovine PRKAG3 locus with meat quality traits in the Chianina breed. No significant association was shown between haploid haplotypes (or diplotypes) and phenotypical traits after applying a Bonferroni correction for multiple comparison. Nonetheless, data from Longissimus dorsi muscle suggest the presence of a statistically non-significant trend toward an influence of the PRKAG3 haploid haplotypes on meat colour (a*) and water holding capacity (M/T) traits, as confirmed also by diplotype-based association analysis. A less clear set of results was observed for the Triceps brachii and Semitendinosus muscles

Long-Lived Plasma Cells and Memory B Cells Produce Pathogenic Anti-GAD65 Autoantibodies in Stiff Person Syndrome

Stiff person syndrome (SPS) is a rare, neurological disorder characterized by sudden cramps and spasms. High titers of enzyme-inhibiting IgG autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GAD65) are a hallmark of SPS, implicating an autoimmune component in the pathology of the syndrome. Studying the B cell compartment and the anti-GAD65 B cell response in two monozygotic twins suffering from SPS, who were treated with the B cell-depleting monoclonal anti-CD20 antibody rituximab, we found that the humoral autoimmune response in SPS is composed of a rituximab-sensitive part that is rapidly cleared after treatment, and a rituximab-resistant component, which persists and acts as a reservoir for autoantibodies inhibiting GAD65 enzyme activity. Our data show that these potentially pathogenic anti-GAD65 autoantibodies are secreted by long-lived plasma cells, which may either be persistent or develop from rituximab-resistant memory B lymphocytes. Both subsets represent only a fraction of anti-GAD65 autoantibody secreting cells. Therefore, the identification and targeting of this compartment is a key factor for successful treatment planning of SPS and of similar autoimmune diseases

Genetic epidemiology of colorectal cancer

Starting from a survey of the studies on familiar aggregation of colorectal cancer, we introduce the aims of genetic epidemiology. One of its main goals is to assess population frequency of cancer susceptibility genes and to determine the age-specific risks for carriers with respect to non-carriers. In section two, segregation analysis investigations are reviewed, and inferences on the relevance of genetic components of susceptibility to colorectal cancer are drawn. In section three, the HNPCC paradigm is discussed in the light of the Knudson model of tumorigenesis and recent advances of molecular research. In the last section we show an example of genotype/environment interaction in the etiology of a particular cancer and present a conceptual framework for studies on cancer genetic epidemiology in terms of attributable and relative risk