trisomy because the broken chromatid may be saved by telomere restitution. In both cases, the inverted duplicated marker forms only after cell division and replication by rejoining the broken, replicated ends of the fragment. It is also suggested that U-type exchange during meiosis I may lead to partial tetrasomy. On the other hand, Class II marker chromosomes result from the second most common type of rearrangement: interstitial deletions. A chromosome is rearranged to give a ring chromosome, and a linear chromosome. Hence, in hindsight, the first observation of neocentromeres made by Andy Choo in 1997 was most likely an example of a Class II pericentric interstitial deletion, followed by a complex rearrangement. The neocentromere can either appear on the linear chromosome or on the ring chromosome, depending on which ever one lacks a centromere. For Class II, it is unclear when the rearrangement occurs. General postulations include the chromosome breaking twice, with the ends rejoining. The alternative argument is that during meiosis I, looping and homologous recombination within a sister chromatid can cause this rearrangement. A rough estimation approximates that neocentromere formation on inverted duplicated chromosomes happens every 70,000–200,000 live births. However, this statistic does not include Class II rearrangements. Neocentromeres in humans and human diseases Human centromeres usually consist of 2000–4000 kilobases of a 171 base pair repeat unit. This alpha satellite is not present at all in human neocentromeres. By 2008, more than 90 reported cases of human neocentromeres were detected on marker chromosomes that experienced a loss of centromere, and a subsequent rearrangement. Common traits among these human neocentromeres include being analphoid, staining C-band negative, containing a primary constriction site, and binding to essential centromere proteins that signal the presence of a kinetochore. Neocentromeres have been detected in human cancers, even though the observed frequency of neocentromeres in the population is relatively low. There is a strong correlation between neocentromeres and a specific class (ALP-WDLPS) of lipomatous tumors. It has been observed that lipomatous tumors with alphoid sequences in the centromere are more aggressive and metastatic. Hence, one suggestion is that neocentromeres may quickly evolve into a centromere with alpha satellite but the correlation between repetitive sequence and aggressiveness of tumors remains unclear. Neocentromeres have also been reported in lung carcinoma and acute myeloid leukemia. It may be worth noting that neocentromeres in cancer may occur more frequently than currently observed, because many cancer screenings involving karyotyping