作者: Rosa Rademakers , Marc Cruts , Kristel Sleegers , Bart Dermaut , Jessie Theuns
DOI: 10.1086/491749
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摘要: We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained population-based study early-onset AD the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses Dutch patient-control sample further supported 7q36. In addition, we identified shared between 1270 three six AD-affected families from same geographical region, which is indicative founder effect defines priority 9.3 cM. Mutation analysis coding exons 29 genes one linked synonymous mutation, g.38030G→C exon 10, that affected codon 626 PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has functional role expression or another mutation this locus explains observed sharing. Together, our data informative strongly support identification novel re-emphasize genetic heterogeneity AD.