Familial transmission of chromoanagenesis leads to unpredictable
unbalanced rearrangements through meiotic recombination
Abstract
Chromoanagenesis are complex chromosomal rearrangements that are
supposed to occur during a single catastrophic event. They may result in
loss or gain of genetic material and may be responsible for various
phenotypes. These rearrangements are usually sporadic. However, some
familial cases have been reported. Here, we studied six families in
which a healthy parent carrying a chromoanagenesis transmitted its
rearrangement in an unbalanced manner to its descent. The rearrangements
were characterized by karyotype, fluorescent in situ
hybridization, chromosomal microarray and whole genome sequencing (WGS)
in the parents and their offspring. We then hypothesized meiosis-pairing
figures of parental chromosomes that may have led to meiotic
recombination between normal and abnormal homologous chromosomes,
resulting in the formation of new unbalanced rearrangements. This work
underlines that chromoanagenesis can be associated with a normal
phenotype and a normal fertility, even in males, and that WGS may be the
unique way to identify these rearrangements in some cases.
Chromoanagenesis can be transmitted in an unbalanced and unpredictable
way because of meiotic recombination. Thus, genetic counseling and
technical choice for prenatal diagnosis are complex. Finally this work
questions the meiotic pairing mechanisms of complex rearrangements,
still poorly understood.