Mutations not inherited from parents cause more than half the cases of schizophrenia

Columbia University Medical Center researchers have shown that new, or ''de novo,'' protein-altering mutations - genetic errors that are present in patients but not in their parents - play a role in more than 50 per cent of ''sporadic'' - ie, not hereditary - cases of schizophrenia. The findings were published online on August 7, 2011, in Nature Genetics.

A group led by Maria Karayiorgou, MD, and Joseph A Gogos, MD, PhD, examined the genomes of patients with schizophrenia and their families, as well as healthy control groups. All were from the genetically isolated, European-descent Afrikaner population of South Africa.

These findings build on earlier studies by Karayiorgou, professor of psychiatry at Columbia University Medical Center. More than 15 years ago, Karayiorgou and her colleagues described a rare de novo mutation that accounts for 1-2 percent of sporadic cases of schizophrenia. With advances in technology, three years ago the Columbia team was able to search the entire genome for similar lesions that insert or remove small chunks of DNA. The mutations found accounted for about 10 percent of sporadic cases.

Encouraged by their progress, they wondered whether other, previously undetectable, de novo mutations accounted for an even greater percentage of sporadic cases.

Using state-of-the-art ''deep sequencing,'' they examined the nucleotide bases of almost all the genes in the human genome. This time they found 40 mutations, all from different genes and most of them protein-altering.

The results point the way to finding more, perhaps even hundreds, of mutations that contribute to the genetics of schizophrenia - a necessary step toward understanding how the disease develops.