Patricia A. Jacobs

I was fortunate to have studied cytogenetics as an undergraduate and this led to my being employed in research in the new field of human cytogenetics. My research has remained focused in this field for over 50 years. The correct number of human chromosomes was first described in 1956 and in 1959 it was shown that additional or missing chromosomes, present in every cell in the body were compatible with life and the cause of a number of clinical syndromes. In 1959 I reported the first human chromosome abnormality, namely the 47,XXY constitution associated with Klinefelter's syndrome, thus demonstrating that (i) the syndrome was the result of an additional X chromosome in males and (ii) the Y chromosome was male determining in mammals. My subsequent research has ranged widely over the whole field of human cytogenetics but has had 3 main foci: 1) the frequency, mechanism of origin and epidemiology of congenital numerical and structural chromosome abnormalities, 2) the phenotype associated with congenital chromosome abnormalities with particular reference to those associated with fetal loss, and 3) studies of the Fragile X syndrome, an X-linked disease causing mental retardation and the first disease shown to be the result of a novel mutational mechanism, namely trinucleotide repeat expansion. This type of mutation is now known to be associated with over 20 neurological diseases in man.