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I have been reading a paper that classifies genes in different groups by the type of disease-causing mutations. The categories of mutations (alleles) it gives are:

  • Haploinsufficient
  • Autosomal dominant
  • autosomal recessive

I was wondering what is the real difference between haploinsufficient and autosomal dominant.

As far as I know, a Haploinsufficient gene is the one that one copy LoF mutation produces the phenotype. This seems to be exactly the same as an Autosomal Dominant disease???

Can someone give me an example?

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Genes can be haploinsufficient, but genes cannot be autosomal dominant, only mutant alleles can be dominant or recessive. If m/+ has a wild type phenotype then the mutant allele ‘m’ is recessive (recessive to the wild type allele ‘+’). However if an m/+ heterozygote has a mutant phenotype then the mutant allele is dominant (dominant over the wild type allele ‘+’) Dominant alleles are usually, but not always, GoF (gain of function). If a gene is haploinsufficient then a heterozygote with a LoF mutant allele over wild type, m/+, has a mutant phenotype, and is dominant but is not a GoF. The classical test is when you have a deletion or deficiency of the gene, and still have one good copy, but still get a mutant phenotype. The autosomal dominant alleles you refer to then have to be GoF, either hypermorphs, antimorphs or neomorphs.

In the model organism, D. melanogaster, the genes Ubx (Ultrabithorax) and N (Notch) are both haploinsufficient, because a heterozygous deficiency of either of those genes have their respective mutant phenotypes. Examples of autosomal dominant mutations in humans are the classical oncogenes, for example the mutant ras gene alleles that cause bladder (and other) cancers.

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    $\begingroup$ In human genetic diseases there are in fact autosomal dominant mutations which upon detailed molecular analysis turn out to be loss-of-function alleles of a haploinsufficient gene. Autosomal dominance is a pattern of inheritance defined by a phenotypic pedigree, it is not a molecular mechanism underlying biological function. Haploinsufficiency, on the other hand, is a description for dose-sensitive genes where two copies of the gene are necessary for a wildtype phenotype. $\endgroup$
    – RosieF
    Nov 16, 2021 at 13:37
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Haploinsufficiency would be like a red and white allele making a pink flower. If the red allele were totally dominant, a flower with one red allele would look exactly the same as one with two red alleles

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  • $\begingroup$ In your example, if the red and white alleles are both dominant gf (gain-of-function) mutations, then what you have described, a flower where both phenotypes are present, is called codominant. A classic example of codominance is in the mating type locus of the baker’s yeast S. cerevisiae. a/a diploids, alpha/alpha diploids, and a/alpha diploids each have different phenotypes. I believe Ira Herskowitz wrote a small review article about this as an example of codominance. $\endgroup$
    – RosieF
    Nov 16, 2021 at 13:29
  • $\begingroup$ Typically, a white allele would be a loss of function; the pigment doesn't get made. A pink flower is pink because it makes less red pigment than the flower with two red alleles. $\endgroup$
    – swbarnes2
    Nov 16, 2021 at 17:14
  • $\begingroup$ The question is about the difference between haploinsuffieicny and complete dominance. Yeast mating types are neither. Co-dominant situations are neither. $\endgroup$
    – swbarnes2
    Nov 16, 2021 at 17:24

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