Genome characterization and CRISPR-Cas9 editing of a human neocentromere

Abstract

The maintenance of genome integrity is ensured by proper chromosome inheritance during mitotic and meiotic cell divisions. The chromosomal counterpart responsible for chromosome segregation to daughter cells is the centromere, at which the spindle apparatus attaches through the kinetochore. Although all mammalian centromeres are primarily composed of megabase-long repetitive sequences, satellite-free human neocentromeres have been described. Neocentromeres and evolutionary new centromeres have revolutionized traditional knowledge about centromeres. Over the past 20 years, insights have been gained into their organization, but in spite of these advancements, the mechanisms underlying their formation and evolution are still unclear. Today, through modern and increasingly accessible genome editing and long-read sequencing techniques, research in this area is undergoing a sudden acceleration. In this article, we describe the primary sequence of a previously described human chromosome 3 neocentromere and observe its possible evolution and repair results after a chromosome breakage induced through CRISPR-Cas9 technologies. Our data represent an exciting advancement in the field of centromere/neocentromere evolution and chromosome stability.

Robertsonian Translocation between Human Chromosomes 21 and 22, Inherited across Three Generations, without Any Phenotypic Effect

“…The emergence of these new centromeres during evolution is associated with the ability to develop new centromeres on a chromosomal region without adversely affecting chromosome functionality [ 66 ]. These silent occurrences of neocentromere formation have been documented in humans, indicating that they are not phenotypically detectable and are often identified incidentally [ 67 , 68 ].…”