[Frequency of rare electrophoretic protein variants in normal human beings and in congenital pathology]

Abstract

17 blood proteins of infants with rough and multiple congenital malformations (CM), prematurely born infants and sick newborns without developmental anomalies were studied electrophoretically in polyacrylamide and starch gels (62422 locus tests). The control included blood samples of healthy newborns from ordinary maternity hospitals (60234 locus tests). The frequency of rare protein variants in all the cases was higher in sick children than in healthy ones. The frequency of rare genes (corrected for electrophoretically "silent" alleles) was 2.16 X 10(-3) in infants with CM and 0.99 X 10(-4) in the control. Examination of parents of 11 congenitally malformed infants with rare protein variants showed that at least in 5 cases such variants were absent in the parents and might be attributed to "fresh" mutations. However, only 3 variants (1 for serum albumin and 2 for red cell esterase) represented rare heterozygotes with codominant expression. This corresponds to the frequency of 0.59 X 10(-3). In the total population of newborns the proportion of infants with CM was 0.02, which means that the population mutation rate is 1.18 X 10(-5) per gene per generation. The data obtained support the conclusion about strong pressure of stabilizing selection against de novo mutations which change electrophoretic mobility of the protein molecule. The reasons for discrepancy between our data and the recent results of Neel and Mohrenweiser (1984) are discussed.