Human chromosome hot points

Summary Peripheral lymphocytes from 16 healthy adults, 9 pregnant women, and 3 fragile X syndrome patients were cultured in Eagle's minimum essential medium without folic acid (MEM-FA). The addition of 2mM, 4mM, or 8mM uridine 24h or 72h prior to harvest resulted in increases of chromosome gaps or breaks, especially at hot points 3p14, 16q23-24, and at fragile site Xq27. Pregnant women showed higher frequencies of 3p14 breaks and total chromosome breaks than men and non-pregnant women. The other chromosome regions, such as 6q26, 7q23, 7q35, 6p25, Xp22, 14q23 and 11p13, also frequently showed gaps or breaks. The results indicated that the unbalance of nucleotide pools was one of the causes of chromosome breakages. The higher frequencies of chromosome gaps and breaks under the condition of thymidylate stress may be due to the misincorporation of uracil instead of thymine into DNA.