GENOMICS: REVOLUTIONIZING MEDICINE

MENDEL — GENETICS

Working in obscurity in the mid-19th century, an Austrian monk quietly formulated some basic principles of a science that would not mature for many decades. Using his monastery garden as a research laboratory, Gregor Mendel bred pea plants to investigate how physical characteristics or traits pass from one generation to the next. His results, carefully quantified and tabulated, led him to two fundamental conclusions.

For each trait he studied, Mendel concluded that a plant had two hereditary units, one from each "parent." He also formulated a theory of dominant and recessive traits — by analyzing the numbers of offspring having different characteristics. Dominant traits, he surmised, are expressed in offspring if either parental plant has the trait. Recessive traits are expressed only when the offspring has received such hereditary units from both parents.

Mendel's breeding experiments — variables and results.

Mendel's units of heredity, now known as genes, were a hypothetical concept that would not be tied to chromosomes (a physical structure) until the 20th century. We now know that a gene consists of a particular sequence of nucleotides in DNA.

Left: Upper-case letters denote dominant "hereditary units." Those in lower case are recessive.

Right: Human chromosomes, with differential banding caused by staining. A correct and precise count of the number of human chromosomes was not firmly established until 1956, when the count was put at 46, or 23 pairs of chromosomes.

Mendel updated — mapping chromosomes and genes. The first genetic map was published in 1913. It showed the relative locations of known drosophila (fruit fly) genes, as derived from statistical linkage analysis. Current research is of a different order of magnitude. This diagram of human chromosome 6, for example, shows the location of the site that codes for the genes of the major histocompatibility complex (MHC). The site spans 4 million base pairs and contains over 100 genes. More detailed maps show the precise locations of individual bases.