The role DNA replication defects play in causing DNA breaks and chromosome rearrangements. Given the parallels between common fragile sites in yeast and human chromosomes, these findings should inform studies to identify genetic determinants of chromosome fragility in humans.
Ultraconserved elements in the human genome are thought to harbor important biological functions. However, their removal in mice is of little consequence.
These investigators test the human consequences of sequence changes in ultraconserved sequences. They report that rare derived alleles of ultraconserved sequences are transmitted from heterozygous parents to offspring in an unbiased way.
That would seem to rule out an immediately and strongly deleterious effect of the rare derived alleles.
Ultraconserved elements in the human genome: Association and transmission analyses of highly constrained single-nucleotide polymorphisms, pp. 253-266 Charleston W. K. Chiang, Ching-Ti Liu, Guillaume Lettre, Leslie A. Lange, Neal W. Jorgensen, Brendan J. Keating, Sailaja Vedantam, Nora L. Nock, Nora Franceschini, Alex P. Reiner, Ellen W. Demerath, Eric Boerwinkle, Jerome I. Rotter, James G. Wilson, Kari E. North, George J. Papanicolaou, L. Adrienne Cupples, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Joanne M. Murabito, and Joel N. Hirschhorn