Human Congenital Diseases with Mixed Modes of Inheritance Have a Shortage of Recessive Disease. A Demographic Scenario?


N. Avrion Mitchison, Institute of Ophthalmology, University College London (UCL), 11–43 Bath St, London EC1V 9EL, UK. Tel.: 020 7608 4056/020 7359 5344; E-mail:


An archive of congenital human diseases is presented, aiming to contain all those where recessive (biallelic) can be compared with X-linked and/or dominant (monoallelic) inheritance. A significant deficit of recessive inheritance is evident, both in disease inheritance and in contribution to inheritance per known disease gene. The deficit contrasts with expectation derived from the cell biology of mutation, and from the importance of recessive mutation in evolution and its preponderance in N-ethyl-N-nitrosourea (ENU) mutagenesis. The deficit fits well with the standard model of demographic change since the neolithic era, and may also reflect natural selection acting on heterozygotes.