The structure and variability of human chromosome ends were investigated using a direct cloning strategy for telomere-associated DNA. The study identified that human chromosomes end with a tandem array of TTAGGG repeats, with some chromosome ends containing additional subtelomeric repeats that are not conserved in rodent DNA. These subtelomeric repeats are present at 10 to 25% of human chromosome ends and are not conserved in rodent DNA, making them useful for physical mapping of human chromosomes in human-rodent hybrid cell lines. The subtelomeric repeat is at least 4 kb in size and shows high variability, with a high frequency of restriction fragment length polymorphisms and de novo methylation in somatic cells. The terminal region of the chromosome, beyond the subtelomeric repeat, consists of a long region of TTAGGG repeats that is highly variable in length. Telomeres in somatic cells are shorter and more heterogeneous than those in sperm, and further shortening is observed in primary tumors, indicating that somatic telomeres are unstable and continuously lose sequences from their ends. Telomeres in human cells are maintained by telomerase, an RNA-dependent DNA polymerase that can elongate telomeres by using an internal RNA component as a template. However, other mechanisms of telomere maintenance may also be involved. The study also found that telomeres in human cells are not conserved in rodent DNA, and that subtelomeric repeats can be used as markers for physical mapping of human chromosomes. The results suggest that the subtelomeric repeat is a common element in a subset of human chromosomes, including chromosomes 7, 16, 17, and 21. The study also identified that telomeres in human cells undergo de novo methylation during the formation of somatic tissues, and that this methylation is not present in sperm DNA. The findings provide important insights into the structure and variability of human chromosome ends, and have implications for understanding the stability and maintenance of telomeres in somatic cells.The structure and variability of human chromosome ends were investigated using a direct cloning strategy for telomere-associated DNA. The study identified that human chromosomes end with a tandem array of TTAGGG repeats, with some chromosome ends containing additional subtelomeric repeats that are not conserved in rodent DNA. These subtelomeric repeats are present at 10 to 25% of human chromosome ends and are not conserved in rodent DNA, making them useful for physical mapping of human chromosomes in human-rodent hybrid cell lines. The subtelomeric repeat is at least 4 kb in size and shows high variability, with a high frequency of restriction fragment length polymorphisms and de novo methylation in somatic cells. The terminal region of the chromosome, beyond the subtelomeric repeat, consists of a long region of TTAGGG repeats that is highly variable in length. Telomeres in somatic cells are shorter and more heterogeneous than those in sperm, and further shortening is observed in primary tumors, indicating that somatic telomeres are unstable and continuously lose sequences from their ends. Telomeres in human cells are maintained by telomerase, an RNA-dependent DNA polymerase that can elongate telomeres by using an internal RNA component as a template. However, other mechanisms of telomere maintenance may also be involved. The study also found that telomeres in human cells are not conserved in rodent DNA, and that subtelomeric repeats can be used as markers for physical mapping of human chromosomes. The results suggest that the subtelomeric repeat is a common element in a subset of human chromosomes, including chromosomes 7, 16, 17, and 21. The study also identified that telomeres in human cells undergo de novo methylation during the formation of somatic tissues, and that this methylation is not present in sperm DNA. The findings provide important insights into the structure and variability of human chromosome ends, and have implications for understanding the stability and maintenance of telomeres in somatic cells.