Europe is the oldest continent and is rapidly aging. The aim of the IP GEHA is to identify genes involved in healthy aging and longevity, allowing individuals to survive to advanced old age in good cognitive and physical function and in the absence of major age-related diseases. To achieve this aim a coherent, tightly integrated program of research that unites demographers, geriatricians geneticists, genetic epidemiologists, molecular biologists, bioinfomaticians and statisticians has been set up. The genetic analysis will be performed by 8 high throughput platforms, within the framework of a centralized database. The working plan of this IP is to: (i) collect an unprecedented number (2550) of long-lived (90+) sibpairs from 10 European countries; (ii) perform a genome scan by microsatellites in all the sibpairs (a total of 5100 individuals) (iii) refine the regions identified by the genome scan by a linkage disequilibrium (LD) mapping using SNPs in cases (i.e. the 2550 probands of the sibpairs) and in 2550 younger controls who will also be recruited, followed by positional cloning and mutational analysis. Three regions in chromosome 4 (D2S1564), 11(11.p15.5) and 19 (around APOE gene) suggested to be involved in aging and longevity in previous studies, will be investigated for their LD block structure in CEPH families and then by an economic number of SNPs in the entire collection of recruited people. All the recruited people will also be genotyped mitochondrial DNA haplogroups and mutations known to play a major role in aging and longevity. Additional advanced approaches (bioinformatics, advanced statistics, mathematical modelling, functional genomics and proteomics, molecular genetics) are envisaged to identify the gene variant(s) of interest. The experimental design will also allow (i) to identify gender-specific genes involved in healthy aging and longevity in women and men; (ii) to develop mathematical and statistical mod#
Keywords:
Healthy ageing, Longevity, Demography, Affected Sib Pair Analysis, Linkage Disequilibrium mapping, Mitochondrial DNA, ApoE, Functional genomics, Proteomics, Gender, Genetic ethical issue.
|
