alexa Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Down Syndrome & Chromosome Abnormalities

Author(s): Percy ME, Markovic VD, Dalton AJ, McLachlan DR, Berg JM,

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Abstract We previously observed low level mosaicism (2-4\% normal cells) in phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) in 29\% of a small group of elderly persons with Down syndrome (DS). An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age. Thus, the "occult" mosaicism in PBL of the elderly persons with DS is likely due to the accumulation of cells that have lost a chromosome 21. A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted. Loss of a chromosome 21 from trisomic cells might result in tissue-specific mosaicism and "classical" mosaicism in different age groups. Chromosome 21 loss might also be relevant to the development of Alzheimer-type dementia in DS and in the general population. This article was published in Am J Med Genet and referenced in Journal of Down Syndrome & Chromosome Abnormalities

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