The Gene / Genealogy Forum II: The Genius of the Genes

Gregor Mendel was fortunate that he was a pea-picker, because he chanced upon a plant in which the wrinkling and the other features were all controlled by single genes, acting independently. Of course the term "gene" was unknown until 1909, and there were many other popular concepts of heredity before scientists began to zero in on DNA. The advent of the microscope brought with it an appreciation of micro-organisms and their complexities. The theory of "spontaneous generation" was widely held before 1865, when Louis Pasteur cast serious doubts upon it. Later in the 19th century, Friedrich Miescher proposed that heredity could be controlled by large molecules of protein.

The Puzzle of Hemophilia
The appearance of a hemorrhagic disease in the family of Queen Victoria of England attracted considerable attention, as it occurred in related royal families and in males who were heirs to various thrones. It first appeared in her son Leopold at the age of twelve. Although he was the eighth of nine children, he was the only one to suffer from a disease which would become known as hemophilia A, or classic hemophilia. He bruised easily, was frequently ill and suffered from a chronic injury to one knee. He survived to adulthood, married and had one daughter, but died shortly after reinjuring his knee. Then Alexis, the son of one Czar Nicholas II of Russia, developed hemophilia. His mother, Alexandra, was a grand-daughter of Queen Victoria. The disease also affected the Spanish Royal Family. Naturally the involvement of inbred royalty resulted in considerable attention to this hemorrhagic disease, long before the defective clotting methods were understood.

Many years later extensive research would show that hemophilia A is caused by a faulty gene located in the X chromosome. But long before this, it was appreciated that the disease is almost entirely limited to males, all of whose sons will be normal and all of whose daughters will be obligatory carriers of the trait. Daughters of these carriers have a 50% chance of also being carriers. Doctors were taught that hemophilia should be suspected from the sex of the patient and the presence of similar cases in the family tree. They confirmed their suspicions by performing various laboratory tests. Although blood platelet function, bleeding time and the number of platelets present were normal, other coagulation tests would show a pattern typical of hemophilia.

Studying diseases such as hemophilia helped define some of the patterns, if not the mechanisms, of heredity. At the same time, puzzling sporadic exceptions occurred in 15 to 20% of the males. Because hemophilia A has a high mutation rate, about a third of these patients have no family history of the disease, nor are any of the lab test of help. The classic inheritance pattern looks like this: