Follow-up mapping supports the evidence for linkage in the candidate region at 9q22 in the NIMH Alzheimer's disease genetics initiative cohort

Rodney T. Perry, Howard Wiener, Lindy E. Harrell, Deborah Blacker, Rudolph E. Tanzi, Lars Bertram, Susan S. Bassett, Rodney C.P. Go

Research output: Contribution to journalArticle

Abstract

Other than the APOE peak at 19q13, the 9q22 region was identified in our original genomic scan as the candidate region with the highest multipoint lod score (MLS) in the subset of late onset Alzheimer's Disease (AD) families (MLS = 2.9 at 101 cM) from the NIMH Genetics Initiative sample. We have now genotyped an additional 12 short tandem repeats (STR) in this region. Multipoint analysis shows the region remains significant with an increase in the peak MLS from 2.9 to 3.8 at 95 cM near marker D9S1815, and the 1 LOD interval narrows from 21.5 to 11 cM. HLOD scores also provide evidence for significant linkage (4.5 with an α = 31%) with a further narrowing of the region to 6.6 cM (92.2-98.8 cM). Single nucleotide polymorphisms (SNPs) in the Ubiquilin1 gene (UBQLN1), located at 83.3 cM, have been reported to be significantly associated to AD, accounting for a substantial portion of the original linkage signal [Bertram et al., 2005]. Our analyses of the higher resolution genotype data generated here provide further support for the existence of a least one additional locus on chromosome 9q22. In an effort to pinpoint this putative AD susceptibility gene, we have begun, to analyze SNPs in other candidate genes in and around this narrowed region to test for additional associations to AD.

Original languageEnglish (US)
Pages (from-to)220-227
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume144
Issue number2
DOIs
StatePublished - Mar 5 2007

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Keywords

  • Chromosome
  • Genomic scan
  • Neurodegenerative
  • SNPs
  • STR

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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