Complete chromosome 21 centromere sequencing of families with Down Syndrome.
Kumara Mastrorosa, F et al. The American Journal of Human Genetics 113, 1381-1398,
July 2026 https://doi.org/10.1016/j.ajhg.2026.05.010
Down syndrome, the most common form of intellectual disability, results from the
presence of an extra copy of chromosome 21 (trisomy 21) due to non-disjunction,
mostly in maternal meiosis. The current hypothesis suggests that the inability of
chromosomes to separate during cell division is due to small centromeres. Testing this
hypothesis has been hampered in part by centromere sequencing challenges. The
authors in this report performed centromere long-read and ultra long sequencing on
cells from eight families with a child with trisomy 21, including cell lines from a triad
(parents-child) obtained from the NIA Aging Cell Repository. Based on their data, the
authors suggest a new hypothesis that centromere asymmetry might be a risk factor for
nondisjunction in Down Syndrome, albeit only in a subgroup of families. However, this is
the first genetic risk factor ever described for Down Syndrome. . The study highlights
the value of biospecimens from well characterized families. The NIA Aging Cell
Repository has unique collections of cells from families with genetic diseases such as
Alzheimer’s, Parkinson’s, premature aging disorders, diabetes, among others. The NIA
Aging Cell Repository cell lines used in this study were: AG16777 (proband), AG16778
(mother), and AG16782 (father).
