Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene

Morphological and genetic characterization of Sardinian trout Salmo cettii Rafinesque, 1810 and their conservation implications

The morphological and genetic structure of Western Mediterranean trout Salmo cettii inhabiting basins in Sardinia was completed to assist the design of its conservation programmes. Genetic analysis of protein-coding LDH-C1 plus sequencing mitochondrial control region gene and analyses of morphological characters described 253 specimens from seven localities in two basins in Southwest Sardinia. Nuclear and mitochondrial analyses revealed all of the fish were pure-bred native S. cettii, with no introgression from allochthonous S. trutta. The novel 18 mtDNA control region haplotypes were clustered in an ‘insular’ clade, strictly related to the Adriatic haplogroup, and depicted a radial network around two ancestral haplotypes. Completion of discriminant analysis using data on body pigmentation and quantitative morphologic parameters revealed three phenotypic groups within the fish. Each population and phenotype, characterised by high values of nucleotide and haplotype diversity, were not genetically differentiated and not geographically structured according to the two hydrological basins. Geometric morphometric analysis, based on 15 landmarkers, revealed pronounced and highly significant differences in body shape morphology between populations, suggesting S. cettii is locally adapting to extreme environmental conditions and so future management plans for these populations should treat the two basins as distinct morphological unit

Mining the pig genome to investigate the domestication process

Pig domestication began around 9000 YBP in the Fertile Crescent and Far East, involving marked morphological and genetic changes that occurred in a relatively short window of time. Identifying the alleles that drove the behavioural and physiological transformation of wild boars into pigs through artificial selection constitutes a formidable challenge that can only be faced from an interdisciplinary perspective. Indeed, although basic facts regarding the demography of pig domestication and dispersal have been uncovered, the biological substrate of these processes remains enigmatic. Considerable hope has been placed on new approaches, based on next-generation sequencing, which allow whole-genome variation to be analyzed at the population level. In this review, we provide an outline of the current knowledge on pig domestication by considering both archaeological and genetic data. Moreover, we discuss several potential scenarios of genome evolution under the complex mixture of demography and selection forces at play during domestication. Finally, we highlight several technical and methodological approaches that may represent significant advances in resolving the conundrum of livestock domestication