Question

The human eye disease retinitis pigmentosa is caused by a loss of function mutation (rp) in the gene PRPF31. The disease is expressed when combined with wildtype allele 1 (rp+1) in a heterozygote, but not expressed when combined with wildtype allele 2 (rp+2) in a heterozygote. When comparing the number PRPF31 mRNA transcripts in the eyes of rp/rp+1 and rp/rp+2 individuals, researchers have found higher number of functional PRPF31 mRNAs in the eyes of rp/rp+2 individuals.

This is an example of                            [ Select ]                       ["incomplete penetrance", "incomplete dominance", "pleiotropy", "variable expressivity"]         caused by                            [ Select ]                       ["haplosufficiency", "haploinsufficiency"]         when is rp occurs in the same genotype as rp+2

Answer 1

Retinitis pigmentosa (RP) is a set of hereditary retinal disorder caused by a loss of function mutation (rp) in the gene PRPF31 (Human pre-mRNA splicing factor 31 (PRPF31). The disease is expressed when combined with wildtype allele 1 (rp+1) in a heterozygote, but not expressed when combined with wildtype allele 2 (rp+2) in a heterozygote. Among inherited retinal dystrophies (IRDs) RP is in itself a large and genetically heterogeneous group of disorders. RP can be transmitted with an autosomal dominant, recessive or X-linked mode of inheritance. The PRPF31, is a ubiquitously expressed component and they are either large deletions or result in a premature termination codon. The mutant transcript is cleared through nonsense-mediated decay (NMD). The photoreceptors are more sensitive to PRPF31 levels due to their high demand on the spliceosome machinery and follow a special splicing program that produces high levels of alternatively spliced transcripts. This is the only cause retinal disease in the heterozygous state. To correlate with protein levels, the mode of action of PRP31 mutations appears to be haploinsuciency, a situation in which the total level of a particular protein produced by the cell is about half of the normal level and that is not sufficient to permit the cell to function normally.

Hence this is an example of incomplete dominance, caused by haploinsufficiency when is rp occurs in the same genotype as rp+2.