Linkage disequilibrium in the 13q12 region in Finnish late onset Alzheimer's disease patients

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder, for which several diseaseassociated loci have been located on different chromosomes. We have used a population-based linkage disequilibrium mapping approach in order to find potential AD-associated loci on chromosome 13. To avoid population stratification, late onset AD patients and age-matched controls were carefully chosen from the same geographical area in Eastern Finland, where the population is mainly descended from a small group of original founders. During the initial screening with chromosome 13-specific microsatellite markers, tetranucleotide marker D13S787 was found to be in linkage disequilibrium in the 13q12 region. Screening this region with additional microsatellite markers revealed that marker D13S292 was also significantly associated with AD. Stratification of the AD patients and controls into groups according to apolipoprotein E, sex, and familial/sporadic status indicated that the 13q12 locus was associated with female familial AD patients regardless of ApoE genotype. Based on the physical data from the region 13q12, markers D13S292 and D13S787 were estimated to reside in a 810 kb long YAC clone 754h7 together with two infant brain-derived ESTs and the H,K-ATPase α-subunit protein gene (ATP1AL1). The localisation of these sequences at the linkage disequilibrium region suggests that they may be candidate genes involved in a sexspecific effect during development of AD.

Genome-Wide Linkage Disequilibrium Mapping of Hypertension in Japan

“…Each of the two large-scale LD mappings of Alzheimer's disease employed approximately 50 cases and 50 controls in their initial mappings (34,35). The numbers of loci detected in their mappings were 6 and 22, respectively (34,35,41,42). In apparent agreement with these numbers, our mapping of hypertension detected 15 loci that were nominally associated with hypertension (Table 3).…”

Genome-wide linkage disequilibrium mapping of late-onset Alzheimer’s disease in Finland

“…13 Sizes of the PCR products were determined with an ABI Prism 310 genetic analyzer (Applied Biosystems) and Genescan 2.1 analysis program (Applied Biosystems). Genomic DNA was isolated from the peripheral blood lymphocytes of patients and control subjects.…”

“…This severely limits the utility of linkage analysis as a mapping tool. 13 To avoid population admixture, the above-mentioned late-onset AD patients and agematched control subjects were chosen from a geographically restricted area in eastern Finland, where the population has descended from a small group of original founders who migrated to the region in the late 16th and early 17th century. 9 It has been suggested that the use of genetically homogeneous populations with a small number of original founders may allow the detection of LD between disease and marker loci over a large chromosomal interval (1 to10 cM) when compared with more admixed, cosmopolitan populations.…”

Polymorphisms in the CYP19 gene confer increased risk for Alzheimer disease

“…[5][6][7][8] These genes are unlikely to fully account for inherited susceptibility for AD. 11,12 We found 22 regions of interest. 11,12 We found 22 regions of interest.…”