That Disturb Hardy-Weinberg Equilibrium

Thus, less than 2% of all the mutant alleles in the population are in affected homozygotes and would therefore be exposed to selection in the absence of effective treatment.

Reduction or removal of selection against an autosomal recessive disorder by successful medical treatment (e.g., as in the case of PKU [see Chapter 12]) would have just as slow an effect on increasing the gene frequency over many generations. Thus as long as mating is random, genotypes in autosomal recessive diseases can be considered to be in Hardy-Weinberg equilibrium, despite selection against homozygotes for the recessive allele. Thus the mathematical relationship between genotype and allele frequencies described in the Hardy-Weinberg law holds for most practical purposes in recessive disease.

Selection in Dominant Disorders.


Examples of Disorders Occurring as Sporadic Conditions due to New Mutations with Zero Fitness

Disorder Description
Atelosteogenesis Early lethal form of short-limbed skeletal dysplasia
Cornelia de Lange syndrome Intellectual disability, micromelia, synophrys, and other abnormalities; can be caused by mutation in the NIPBL gene
Osteogenesis imperfecta, type II Perinatal lethal type, with a defect in type I collagen (COL1A1, COL1A2) (see Chapter 12)
Thanatophoric dysplasia Early lethal form of skeletal dysplasia due to de novo mutations in the FGFR3 gene (see Fig. 7-6C)

Mutation and Selection Balance in Dominant Disease.



As an illustration of this relationship, in achondroplasia, the fitness of affected patients is not zero, but they have only approximately one fifth as many children as people of normal stature in the population. Thus their average fitness, f, is 0.20, and the coefficient of selection, s, is 1 − f, or 0.80. In the subsequent generation, then, only 20% of current achondroplasia alleles are passed on from the current generation to the next. Because the frequency of achondroplasia appears stable from generation to generation, new mutations must be responsible for replacing the 80% of mutant genes in the population lost through selection.

If the fitness of affected persons suddenly improved (e.g., because of medical advances), the observed incidence of the disease in the population would be predicted to increase and reach a new equilibrium. Retinoblastoma (Case 39and other dominant embryonic tumors with childhood onset are examples of conditions that now have a greatly improved prognosis, with a predicted consequence of increased disease frequency in the population. Allele frequency, mutation rate, and fitness are related; thus, if any two of these three characteristics are known, the third can be estimated.

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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on That Disturb Hardy-Weinberg Equilibrium

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