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Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.

Publication ,  Journal Article
Pericak-Vance, MA; Bebout, JL; Gaskell, PC; Yamaoka, LH; Hung, WY; Alberts, MJ; Walker, AP; Bartlett, RJ; Haynes, CA; Welsh, KA
Published in: Am J Hum Genet
June 1991

A genetic component in the etiology of Alzheimer disease (AD) has been supported by indirect evidence for several years, with autosomal dominant inheritance with age-dependent penetrance being suggested to explain the familial aggregation of affecteds. St. George Hyslop et al. reported linkage of familial AD (FAD) in four early-onset families (mean age at onset [M] less than 50 years). Subsequent studies have been inconsistent in their results; Goate et al. also reported positive lod scores. However, both Pericak-Vance et al.'s study of a series of mainly late-onset FAD families (M greater than 60 years) and Schellenberg et al.'s study failed to confirm linkage to chromosome 21 (CH21). These various studies suggest the possibility of genetic heterogeneity, with some families linked to CH21 and others unlocalized. Recently, St. George Hyslop et al. extended their analysis to include additional families. The extended analyses supported their earlier finding of linkage to CH21, while showing strong evidence of heterogeneity between early-onset (M less than 65 years) and late-onset (M greater than 60 years) FAD families. Because our families did not show linkage to CH21, we undertook a genomic search for an additional locus for FAD. Because of both the confounding factor of late age at onset of FAD and the lack of clear evidence of Mendelian transmission in some of our families, we employed the affected-pedigree-member (APM) method of linkage analysis as an initial screen for possible linkage. Using this method, we identified two regions suggesting linkage: the proximal long arm of chromosome 19 (CH19) and the CH21 region of FAD linkage reported by St. George Hyslop et al. Application of standard likelihood (LOD score) analysis to these data support the possibility of an FAD gene locate on CH19, particularly in the late-onset FAD families. These data further suggest genetic heterogeneity and delineate this region of CH19 as an area needing additional investigation in FAD.

Duke Scholars

Published In

Am J Hum Genet

ISSN

0002-9297

Publication Date

June 1991

Volume

48

Issue

6

Start / End Page

1034 / 1050

Location

United States

Related Subject Headings

  • Pedigree
  • Middle Aged
  • Lod Score
  • Humans
  • Genetics & Heredity
  • Genetic Linkage
  • DNA
  • Chromosomes, Human, Pair 19
  • Chromosome Mapping
  • Alzheimer Disease
 

Citation

APA
Chicago
ICMJE
MLA
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Pericak-Vance, M. A., Bebout, J. L., Gaskell, P. C., Yamaoka, L. H., Hung, W. Y., Alberts, M. J., … Welsh, K. A. (1991). Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Hum Genet, 48(6), 1034–1050.
Pericak-Vance, M. A., J. L. Bebout, P. C. Gaskell, L. H. Yamaoka, W. Y. Hung, M. J. Alberts, A. P. Walker, R. J. Bartlett, C. A. Haynes, and K. A. Welsh. “Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.Am J Hum Genet 48, no. 6 (June 1991): 1034–50.
Pericak-Vance MA, Bebout JL, Gaskell PC, Yamaoka LH, Hung WY, Alberts MJ, et al. Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Hum Genet. 1991 Jun;48(6):1034–50.
Pericak-Vance, M. A., et al. “Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.Am J Hum Genet, vol. 48, no. 6, June 1991, pp. 1034–50.
Pericak-Vance MA, Bebout JL, Gaskell PC, Yamaoka LH, Hung WY, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA. Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Hum Genet. 1991 Jun;48(6):1034–1050.
Journal cover image

Published In

Am J Hum Genet

ISSN

0002-9297

Publication Date

June 1991

Volume

48

Issue

6

Start / End Page

1034 / 1050

Location

United States

Related Subject Headings

  • Pedigree
  • Middle Aged
  • Lod Score
  • Humans
  • Genetics & Heredity
  • Genetic Linkage
  • DNA
  • Chromosomes, Human, Pair 19
  • Chromosome Mapping
  • Alzheimer Disease