Mutations at the disease locus arise all the time, and (in homozygotes for recessive mutations, or heterozygotes for dominant mutations) cause disease.
A mutation was considered transient if its frequency subsequently decreased below 100% for complete mutations, or below 50% for dominant mutations, or if minor mutations disappeared over the observation period; e.g, a minor transient mutation is outlined at position 419 in Figure 2B.
To further elucidate the cataract phenotype, and identify the gene and mutation for autosomal dominant cataract (ADC) in an American family of European descent (ADC2) by sequencing the major intrinsic protein gene (MIP), a candidate based on linkage to chromosome 12q13.
To recover mutations that affect pairing-sensitive silencing, we screened for dominant mutations that suppressed en 181bp-mediated mini- white repression.
This can, for example, classify mutations that are potentially allelic, which is particularly useful for dominant mutations, and allows isolation of the affected genes on the basis of their positions.
These studies indicate that recurrence in families in which a child with lethal OI is born is increased as a result of parental carrier status for recessive mutations in addition to the well-known risk of parental mosaicism for dominant mutations.
For example, we would expect to see more fixation of proviruses on X for recessive mutations that are of benefit to males but harmful to females or for dominant mutations that are of benefit to females but harmful to males [ 30].
We alter gene expression on a genome-wide scale by selecting for dominant mutations in a randomly mutagenized general transcription factor.
For dominant mutations, gene dosage is a common factor affecting the phenotype, in that homozygotes, if viable, are more likely to exhibit extreme characteristics.
Our lab, and others, have conducted genetic screens for dominant mutations that suppress this gene silencing [Su var)s][18] [23]. Between 30 and 50 loci can be mutated to produce the Su var) phenotype.
