Simons Center for Systems Biology

By John Hopfield 

From Rudyard Kipling's "Just So" story "The Elephant's Child"

All of us who have watched as a friend or relative has disappeared into the fog of Alzheimer’s arrive at the same truth. Although we recognize people by their visual appearance, what we really are as individual humans is determined by how our brains operate. The brain is certainly the least understood organ in the human body. If you ask a cardiologist how the heart works, she will give an engineering description of a pump based on muscle contraction and valves between chambers. If you ask a neurologist how the brain works, how thinking takes place, well . . . Do you remember Rudyard Kipling’s Just So Stories, full of fantastical evolutionary explanations, such as the one about how the elephant got its trunk? They are remarkably similar to a medical description of how the brain works.

The annual meeting of the Society for Neuroscience attracts over thirty thousand registrants. It is not for lack of effort that we understand so little of how the brain functions. The problem is one of the size, complexity, and individuality of the human brain. Size: the human brain has approximately one hundred billion nerve cells, each connecting to one thousand others. Complexity: there are one hundred different types of nerve cells, each with its own detailed properties. Individuality: all humans are similar, but the operation of each brain is critically dependent on its individual details. Your particular pattern of connections between nerve cells contains your personality, your language skills, your knowledge of family, your college education, and your golf swing.

By Chang S. Chan, Suzanne Christen, and Asad Naqvi 

This plot of genetic data from an individual with autism shows a deletion in the gene NCAM2, one of four genes that researchers in the Simons Center for Systems Biology found to be associated with autism.

Autism is a common child­hood neurodevelop­mental disorder affecting one in 180 children. It is characterized by impaired social interaction and communication, and by restric­ted interests and rep­etitive behav­ior. Autism is a complex disease exhibiting strong genetic liability with a twenty-five-fold increas­ed risk for individuals having affected first-degree relatives. Moreover, the concordance for developing autism is over 90 percent in identical twins, but only 5–10 percent for fraternal twins. Recent advances in genetics show that autism is associated with many diverse genes, with each gene accounting only for a few percent of cases, as well as complicated multigenic effects.

Researchers at the Simons Center for Systems Biology have been studying autism for the past two years. We have identified novel genes associated with autism. Our approach is to use single nucleotide polymorphism (SNP) genotyping chips that measure differences between individuals and can uncover candidate genes or regulatory elements (which control gene activity) associated with the disease.

Most individuals differ very little from one another across the human genome. SNPs are the largest class of DNA sequence variation among individuals. A SNP occurs when one base out of the four bases used in DNA is exchanged for another base at the same locus, such that the minor allele frequency is at least 1 percent in a given population. SNPs are found at the rate of roughly one out of every 1,000 base pairs of the human genome. These SNPs provide the best chance of detecting genetic variation, both normal and otherwise, between people.