Researchers at The Children's Hospital of Philadelphia continue exploration of chromosome 22
Philadelphia, Pa. -- Chromosome 22, one of the smallest human chromosomes, is known to be a hot spot for disease, including heart defects, leukemias and schizophrenia. Genetics researchers at The Children's Hospital of Philadelphia are teasing out details of how that chromosome's chemical structure renders it particularly vulnerable to defects and rearrangements that may result in diseases. Their latest study focuses on a rare inherited condition called +der(22) syndrome that includes mental retardation, a heart defect, a small chin, and a cleft or abnormal palate. The researchers described unusual, unstable DNA structures in parents of children with the disease.
Reporting in the July issue of Human Molecular Genetics, the research team isolated specific DNA sequences at the junctions where broken pieces of chromosomes 11 and 22 attach to each other in a rearrangement called a translocation. The researchers found unusually frequent sequences of adenine and thymine, two of the four chemical letters in the genetic alphabet that spells out the body's blueprint. These repetitive stretches are called AT rich repeats and are arranged in an unusual configuration called a palindrome. "These palindromic sequences are unstable, and allow us to propose a model for how this translocation occurs," said Beverly S. Emanuel, Ph.D., chief of Human Genetics and Molecular Biology at The Children's Hospital of Philadelphia and senior author of the paper.
"This model of the disease's origin in chromosome structure is important not only for understanding +der(22) syndrome, but also may assist us in understanding other translocations," said Dr. Emanuel. Other diseases associated with such translocations in chromosomes include certain types of cancer and other birth defects. Children's Hospital treats hundreds of patients each year for genetic diseases.
Contact: Kajsa Haracz
Children's Hospital of Philadelphia