Linkage analysis of familial Alzheimer disease, using chromosome 21 markers

Gerard D. Schellenberg, Margaret A Pericak-Vance, Ellen M. Wijsman, Deborah K. Moore, Perry C. Gaskell, Larry A. Yamaoka, Jacqueline L. Bebout, Leojean Anderson, Kathleen A. Welsh, Christopher M. Clark, George M. Martin, Allen D. Roses, Thomas D. Bird

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Abstract

Chromosome 21 markers were tested for linkage to familial Alzheimer disease (FAD) in 48 kindreds. These families had multiple cases of Alzheimer disease (AD) in 2 or more generations with family age-at-onset means (M) ranging from 41 to 83 years. Included in this group are seven Volga German families which are thought to be genetically homogeneous with respect to FAD. Autopsy documentation of AD was available for 32 families. Linkage to the 21 q11-q21 region was tested using D21S16, D21S13, D21S110, D21S1/S11, and the APP gene as genetic markers. When linkage results for all the families were summed, the LOD scores for these markers were consistently negative and the entire region was formally excluded. Linkage results were also summed for the following family groups; late-onset (M > 60), early-onset (M ≤ 60), Volga Germans (M = 56), and early-onset non-Volga Germans (M ≤; 60). For the first three groups, LOD scores were negative for this region. For the early-onset non-Volga German group (six families), small positive LOD scores of Zmax = 0.78 (recombination fraction θ = .15), Zmax = 0.27 (θ = .15), and Zmax = 0.64 (θ = .0), were observed for D21S13, D21S16, and D21S110, respectively. The remainder of the long arm of chromosome 21 was tested for linkage to FAD using seven markers spanning the q22 region. Results for these markers were also predominantly negative. Thus it is highly unlikely that a chromosome 21 gene is responsible for late-onset FAD and at least some forms of early-onset FAD represented by the Volga German kindreds.

Original languageEnglish
Pages (from-to)563-583
Number of pages21
JournalAmerican Journal of Human Genetics
Volume48
Issue number3
StatePublished - Mar 1 1991
Externally publishedYes

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Chromosomes, Human, Pair 21
Genetic Markers
Alzheimer Disease
Age of Onset
Documentation
Genetic Recombination
Genes
Autopsy
Alzheimer disease type 2

ASJC Scopus subject areas

  • Genetics

Cite this

Schellenberg, G. D., Pericak-Vance, M. A., Wijsman, E. M., Moore, D. K., Gaskell, P. C., Yamaoka, L. A., ... Bird, T. D. (1991). Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. American Journal of Human Genetics, 48(3), 563-583.

Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. / Schellenberg, Gerard D.; Pericak-Vance, Margaret A; Wijsman, Ellen M.; Moore, Deborah K.; Gaskell, Perry C.; Yamaoka, Larry A.; Bebout, Jacqueline L.; Anderson, Leojean; Welsh, Kathleen A.; Clark, Christopher M.; Martin, George M.; Roses, Allen D.; Bird, Thomas D.

In: American Journal of Human Genetics, Vol. 48, No. 3, 01.03.1991, p. 563-583.

Research output: Contribution to journalArticle

Schellenberg, GD, Pericak-Vance, MA, Wijsman, EM, Moore, DK, Gaskell, PC, Yamaoka, LA, Bebout, JL, Anderson, L, Welsh, KA, Clark, CM, Martin, GM, Roses, AD & Bird, TD 1991, 'Linkage analysis of familial Alzheimer disease, using chromosome 21 markers', American Journal of Human Genetics, vol. 48, no. 3, pp. 563-583.
Schellenberg GD, Pericak-Vance MA, Wijsman EM, Moore DK, Gaskell PC, Yamaoka LA et al. Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. American Journal of Human Genetics. 1991 Mar 1;48(3):563-583.
Schellenberg, Gerard D. ; Pericak-Vance, Margaret A ; Wijsman, Ellen M. ; Moore, Deborah K. ; Gaskell, Perry C. ; Yamaoka, Larry A. ; Bebout, Jacqueline L. ; Anderson, Leojean ; Welsh, Kathleen A. ; Clark, Christopher M. ; Martin, George M. ; Roses, Allen D. ; Bird, Thomas D. / Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. In: American Journal of Human Genetics. 1991 ; Vol. 48, No. 3. pp. 563-583.
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abstract = "Chromosome 21 markers were tested for linkage to familial Alzheimer disease (FAD) in 48 kindreds. These families had multiple cases of Alzheimer disease (AD) in 2 or more generations with family age-at-onset means (M) ranging from 41 to 83 years. Included in this group are seven Volga German families which are thought to be genetically homogeneous with respect to FAD. Autopsy documentation of AD was available for 32 families. Linkage to the 21 q11-q21 region was tested using D21S16, D21S13, D21S110, D21S1/S11, and the APP gene as genetic markers. When linkage results for all the families were summed, the LOD scores for these markers were consistently negative and the entire region was formally excluded. Linkage results were also summed for the following family groups; late-onset (M > 60), early-onset (M ≤ 60), Volga Germans (M = 56), and early-onset non-Volga Germans (M ≤; 60). For the first three groups, LOD scores were negative for this region. For the early-onset non-Volga German group (six families), small positive LOD scores of Zmax = 0.78 (recombination fraction θ = .15), Zmax = 0.27 (θ = .15), and Zmax = 0.64 (θ = .0), were observed for D21S13, D21S16, and D21S110, respectively. The remainder of the long arm of chromosome 21 was tested for linkage to FAD using seven markers spanning the q22 region. Results for these markers were also predominantly negative. Thus it is highly unlikely that a chromosome 21 gene is responsible for late-onset FAD and at least some forms of early-onset FAD represented by the Volga German kindreds.",
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