Lap-Chee Tsui

(b. 1950)

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(1950–) Chinese–Canadian molecular biologist

Tsui was born at Shanghai in China and educated at the Chinese University, Hong Kong, and at the University of Pittsburgh, where he obtained his PhD in 1979. He joined the staff of the Hospital for Sick Children, Toronto, in 1980 and has continued to work there while also holding (since 1990) a professorship of medical genetics at the University of Toronto.

In 1989, in collaboration with his Toronto colleagues Jack Riordan and Francis Collins of the University of Michigan and against strong competition, Tsui announced that he had located the cystic fibrosis gene. Cystic fibrosis (CF) is caused by a recessive gene widely distributed among Caucasians; about 1000 children with CF are born in the United States each year. The disease affects secretory epithelia and, until recently, patients tended to die from lung infections and heart failure in their twenties.

When Tsui arrived in Toronto in 1980 new techniques were being proposed which, if effective, should allow defective genes to be identified. The procedure, introduced by Ray White and his colleagues, involved identifying an appropriate RFLP (restriction fragment length polymorphism), i.e., a fragment of DNA for use as a genetic marker to locate the site of the defective gene. The difficulty was that the human genome contains 3 billion base pairs of DNA; it was, therefore, a very remote possibility that any genetic marker would be within a reasonable distance of the CF gene. The chances would, however, be much improved if it was known on which chromosome the gene was sited. This was established as chromosome 7 by a Massachusetts biotechnology firm, Collaborative Research Inc (CRI), in 1985.

Thereafter it was a matter of using the available probes to focus on the area in which the gene could be found. By 1989 it had been narrowed to 300,000 base pairs. Further work demonstrated that the defective gene encoded a membrane protein of 1480 amino acids and has been dubbed the CF transmembrane conductance regulator (CFTR). Tsui and his colleagues have shown that a loss of one amino acid one third of the way along the gene is responsible for 68% of cases of CF. He has continued to search for the mutations responsible for the other cases and has also sought to understand at the molecular level variations in the severity of the disease.

Subjects: Science and Mathematics.

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