TY - JOUR
T1 - β-Amyloid gene is not present in three copies in autopsy-validated Alzheimer's disease
AU - Warren, Andrew C.
AU - Robakis, Nikolaos K.
AU - Ramakrishna, Narayanarao
AU - Koo, Edward H.
AU - Ross, Christopher A.
AU - Robb, Adelaide S.
AU - Folstein, Marshal F.
AU - Price, Donald L.
AU - Antonarakis, Stylianos E.
N1 - Funding Information:
The authors thank Dr. Robert G. Struble for preparation of frozen brain tissues, Dr. Gary R. Cutting for assistance with pulsed-field electrophoresis, Dr. Michael D. Applegate for assistance in computer-imaging technology, and Drs. Ernest Barbosa and Linda C. Cork for helpful discussions. This work was supported by grants from the U.S. Public Health Service (NIH HD 19591, AG 03359, AG 05146, NS 20471) as well as funds from The Commonwealth Fund, the Claster family, the Robert L. & Glara G. Patterson Trust, and the John Douglas French Foundation for Research in Alzheimer’s Disease. Dr. Price is the recipient of a Javits Neuroscience Investigator Award (NIH NS 10580).
PY - 1987/12
Y1 - 1987/12
N2 - Recently, it has been suggested that Alzheimer's disease is associated with a duplication of the amyloid precursor protein gene localized to chromosome 21q21. In this study, a cloned DNA probe (B2.3), complementary to the sequence coding the β-amyloid peptide, and DNA polymorphisms adjacent to this sequence were used to determine the number of copies of the β-amyloid gene in DNA isolated from human blood and brain. Individuals with trisomy 21 (Down syndrome) who were heterozygous for the polymorphisms showed a gene-dosage effect, with one allele exhibiting twice the autoradiographic intensity as the other. Heterozygous individuals with Alzheimer's disease and controls showed equal intensities of the two allelic bands, suggesting that there are only two copies of the β-amyloid gene in these individuals. In individuals with Alzheimer's disease and in controls who were homozygous for these polymorphisms, the number of copies of the β-amyloid gene was determined by comparing the autoradiographic intensity of β-amyloid alleles to that of DNA fragments detected by a reference probe. No difference was detected between these two groups.
AB - Recently, it has been suggested that Alzheimer's disease is associated with a duplication of the amyloid precursor protein gene localized to chromosome 21q21. In this study, a cloned DNA probe (B2.3), complementary to the sequence coding the β-amyloid peptide, and DNA polymorphisms adjacent to this sequence were used to determine the number of copies of the β-amyloid gene in DNA isolated from human blood and brain. Individuals with trisomy 21 (Down syndrome) who were heterozygous for the polymorphisms showed a gene-dosage effect, with one allele exhibiting twice the autoradiographic intensity as the other. Heterozygous individuals with Alzheimer's disease and controls showed equal intensities of the two allelic bands, suggesting that there are only two copies of the β-amyloid gene in these individuals. In individuals with Alzheimer's disease and in controls who were homozygous for these polymorphisms, the number of copies of the β-amyloid gene was determined by comparing the autoradiographic intensity of β-amyloid alleles to that of DNA fragments detected by a reference probe. No difference was detected between these two groups.
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U2 - 10.1016/0888-7543(87)90029-2
DO - 10.1016/0888-7543(87)90029-2
M3 - Article
C2 - 2966761
AN - SCOPUS:0023497512
SN - 0888-7543
VL - 1
SP - 307
EP - 312
JO - Genomics
JF - Genomics
IS - 4
ER -