Heterogeneity of the Silent Gene for Plasma Cholinesterase

Abstract

Rocket immuno-electrophoresis and enzyme-linked immunosorbent assays were used to estimate the amount of cholinesterase present in 29 apparent silent homozygotes. 26 of these samples were segregated into four groups representing zero, very low, low and high levels of immunoreactive protein. These groups may represent the genotypes E^s₁, E^s₁, E^s₁, E^t₁, Ε^t₁, E^t₁ and a new genotype E^x₁, E^x₁, respectively. The possible genotypes of the remaining 3 individuals are discussed.

Immunological Studies of Families Segregating the Silent Gene for Plasma Cholinesterase

“…It is re markable that the E|k gene appears to be segregating in the 3 families each having the propositus with genotype E|SE|', and although this is a striking result we attach no significance to this segregation within these families until more data are avail able. Our earlier studies [Whittaker et al, 1990] indicated that 2 of the propositi (CH and MS) in families 5 and 7 appeared to be segregating the new silent gene E |\ The propositus 11-1 (KM) and her brother 11-2 in family 5 each show a high percentage protein binding ratio with MAb 2-1 and MAb 2-4, although the enzymic activities are very low, and from this we deduce that the E |' gene is segregating in this family. The ELISA results for their mother 1-1 with either MAb2-l or MAb 2-4 are low and so it is extremely improbable that she is segregating the E|x gene.…”

“…Three families (2, 3 and 4) appear to be segregating both the E f and Ef genes in the propositus. One of them, 11-1 (KQ, family 2), has been phenotyped as E fE f in our earlier survey [Whittaker et al, 1990] and one of his siblings (11-4) has the same genotype. In this family the father 1-1 is segregating a usual gene E f but it is diffi cult to assign either the E f or Ef gene to the father 1-1 in preference to the mother 1-2.…”

“…In our earlier paper [Whittaker et al, 1990] we proposed that 4 individuals, which included CH and DS from families 6 and 7, respectively, were segregating a new gene E f and that these 4 individuals were probably homozygotes E|X E|X . Our family studies have indicated that CH and DS are, in fact, heterozygotes with prob able genotype E |'E |\ All 4 individuals in our previous study had very similar immunoprotein binding ratios by ELISA with MAb 2-1 and MAb2-4.…”

“…These are E ,\ Ei1 and E|r [Scott, 1973;Scott and Wright, 1976]. An enzymelinked immunosorbent assay (ELISA) has been developed and used to separate 29 apparently silent homozygotes into 4 groups which probably represent the genotypes E,SE |\ E|SE|', E /E / and a new variant E|X E|X [Whittaker et al, 1990]. We have extended our ELISA studies to the families of 7 'silent' homozygotes in order to substantiate our early hypothesis.…”

“…1990). Cholinesterase activity was as sayed by a microplate modified Ellman reaction [Ellman et al, 1961] with butyrylthiocholine substrate [Whittaker et al, 1990).…”