Alzheimer Disease 14


For a general phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease, see 104300.


In a genome screen of individuals from an isolated population from the southwestern area of the Netherlands, ascertained as part of the Genetic Research in Isolated Populations (GRIP) program, Liu et al. (2007) found the strongest evidence of linkage for chromosome 1q21 (AD13; 611152). Approximately 30 cM upstream of this locus, at 1q25, another peak (AD14) was found (hlod = 4.0 at marker D1S218). Liu et al. (2007) noted that these 2 loci were in a linkage region spanning 1q21-q31 identified by Zubenko et al. (1998), Hiltunen et al. (2001), Myers et al. (2002), and Blacker et al. (2003). Haplotype analysis showed that the 2 linkage peaks on chromosome 1q21 and 1q25 are explained by different haplotypes, of 15 cM and 21 cM, respectively, segregating in different families. The 1q25 region was confirmed when testing for association with cognitive function as an endophenotype of AD in 197 distantly related subjects. The study indicated that potential disease-causing genes at 1q25 are RGSL2 (611013), RALGPS2 (617819), and C1ORF49.