Mutation screening of a haplotype block around the insulin degrading enzyme gene and association with Alzheimer's disease.

Abstract

Genetic and biological studies point to a role for insulin-degrading enzyme (IDE) in Alzheimer's disease (AD). Two SNP-based studies recently reported evidence for association with AD using markers in a approximately 270 kb haplotype block on chromosome 10q. This haplotype block region harbors three known genes; insulin-degrading enzyme (IDE), kinesin family member 11 (KIF11), and hematopoietically expressed homeobox (HHEX). In an attempt to search for susceptibility variants we have sequenced all coding exons, 2 kb of 5' and 3'-flanking sequence, and all regions showing a high degree of human-mouse conservation in these three genes in 30 individuals. We found a total of 40 single nucleotide polymorphisms and 8 insertion/deletion polymorphisms. No coding variants were identified in any of the three genes. Nine polymorphisms in IDE and four polymorphisms in KIF11 situated in conserved regions or near coding exons were subsequently genotyped in a set of AD cases and controls. Two markers in KIF11 yielded borderline significant results in the ApoE4 non-carrier subgroup, but the results were otherwise not significant in this small set of samples. This study of multiple new markers in the region will facilitate further association studies in this important AD region.

• Authors: Lars Feuk, Shane McCarthy, Björn Andersson, Jonathan A Prince, Anthony J Brookes
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 136B Issue 1 Pg. 69-71 (Jul 05 2005) ISSN: 1552-4841 [Print] United States
• PMID: 15858821 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2005 Wiley-Liss, Inc.

Chemical References

• Genetic Markers
• Homeodomain Proteins
• Insulysin
• Kinesins

Topics

• Alzheimer Disease (enzymology, genetics)
• Animals
• Chromosomes, Human, Pair 10 (genetics)
• Gene Frequency
• Genetic Markers (genetics)
• Haplotypes (genetics)
• Homeodomain Proteins (genetics)
• Humans
• Insulysin (genetics)
• Kinesins (genetics)
• Linkage Disequilibrium
• Mice
• Mutation
• Polymorphism, Single Nucleotide