As the basis for the lifelong clock and as a primary cause of aging, a process of shortening of hypothetical perichromosomal DNA structures termed chronomeres is proposed in the CNS. The lifelong clock is regulated by the shortening of chronomere DNA in postmitotic neurons of the hypothalamus. Shortening of these DNA sequences occurs in humans on a monthly basis through a lunasensory system and is controlled by release of growth hormone discharged from the anterior pituitary directly into the hypothalamus via local blood vessels.
Developmentally controlled genomic deletion-ligations occur during ciliate macronuclear differentiation. We have identified a novel activity in Tetrahymena cell-free extracts that efficiently catalyzes a specific set of intramolecular DNA deletion-ligation reactions. When synthetic DNA oligonucleotide substrates were used, all the deletion-ligation products resembled those formed in vivo in that they resulted from deletions between pairs of short direct repeats. The reaction is ATP-dependent, salt-sensitive, and strongly influenced by the oligonucleotide substrate sequence.
We analyzed sites of macronuclear telomere addition at a single genetic locus in Paramecium tetraurelia. We showed that in homozygous wild-type cells, differential genomic processing during macronuclear development resulted in the A surface antigen gene being located 8, 13, or 26 kilobases upstream from a macronuclear telomere. We describe variable rearrangements that occurred at the telomere 8 kilobases from the A gene. A mutant (d48) that forms a telomere near the 5' end of the A gene was also analyzed.
The autonomously replicating rRNA genes (rDNA) in the somatic nucleus of Tetrahymena thermophila are maintained at a copy number of approximately 10(4) per nucleus. A mutant in which the replication properties of this molecule were altered was isolated and characterized. This mutation of inbred strain C3, named rmm4, was shown to have the same effect on rDNA replication and to be associated with the same 1-base-pair (bp) deletion as the previously reported, independently derived rmm1 mutation (D. L. Larson, E. H. Blackburn, P. C. Yaeger, and E. Orias, Cell 47:229-240, 1986).
OBJECTIVES: Variation in the human genome may explain genetic contributions to complex traits and common diseases. FINDINGS: Until recently, single nucleotide polymorphisms were thought to be the most prevalent form of interindividual genetic variation. However, structural genomic rearrangements such as deletions, duplications, and inversions lead to variation in gene copy number and contribute even more to genomic diversity. Other sources of genomic variation include noncoding genes, pseudogenes, and mobile genetic elements (transposons).
Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans. It is typified by highly variable symptoms, which might be explained by epigenetic regulation of genes in the interval. Using computational algorithms, our laboratory previously predicted that DiGeorge critical region 6 (DGCR6), which lies within the deletion interval, is imprinted in humans. Expression and epigenetic regulation of this gene have not, however, been examined in 22q11DS subjects.