Evidence for sex-linked lethal factors in man

Abstract

Among the points brought to light during the investigations which followed the rediscovery of Mendel's Law of Heredity were two of especial interest to medical men. These were lethal factors and sex-linked inheritance.

A lethal factor is a Mendelian unit which can be carried by a normal individual as can any recessive, but which when present without its normal allelomorph to balance it, causes the death of the individual possessing it. Among those lethal factors demonstrated for mammals is that for yellow coat color in mice. The color of the wild house mouse is called by geneticists “black agouti.” It has as an alternative condition or allelomorph, a type in which almost if not all, black and brown pigment has disappeared from the coat leaving only the yellow pigment unmodified. When black agouti mice are crossed together yellows are never produced. When yellows are crossed together however, yellows and black agoutis are produced in a ratio of 2 to 1. If the yellows had been ordinary mendelian heterozygotes, the ratio should have been 3 to 1, but it is clear that the 2 to 1 ratio is the one involved. The obvious hypothesis is that the homozygous yellow individuals start their development, but perish in early embryonic stages. This suggestion was therefore made by Castle and Little (1910) and has since been supported by the histological and embryological findings of Kirkham, Ibsen and others.

The case may be diagrammed as follows:

Sex-linked inheritance is slightly more complicated but has been completely demonstrated. The approximate equality of male and female individuals which characterizes most species of the higher animals, is strongly suggestive of the I : I mendelian ratio. This ratio is obtained in mendelian inheritance when a DR individual is crossed with either a DD or an RR individual.