Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease.
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.
Percy
M E
ME
Surrey Place Centre, Toronto, Ontario, Canada.
Markovic
V D
VD
Dalton
A J
AJ
McLachlan
D R
DR
Berg
J M
JM
Rusk
A C
AC
Somerville
M J
MJ
Chodakowski
B
B
Andrews
D F
DF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics; D000782:Aneuploidy; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009030:Mosaicism