Is Huntington's Disease Dominant with Hh or HH?

[Math Is Hard]

We were doing Punnett squares in my bio class the other night and one of the problems I was working out was about chances of a person inheriting Huntington's chorea.

I thought I had done the problem correctly. Since Huntington's is a dominant disease, I counted any resulting Hh genotypes (one dominant and one recessive allele) as having Huntington's. But then the teacher worked the problem out and said that the genotype would have to be HH (the person MUST have BOTH dominant alleles) in order for the person to have Huntington's chorea. I am completely confused now.

I did some Googling and what I am finding seems to support my original assumptions. For instance this:

http://evolution.berkeley.edu/evolibrary/article/0_0_0/medicine_05

And I have looked at some other sites which state that an individual inheriting the HH genotype has a very low chance of survival, and will not make it to adulthood.

Can anyone help me understand this? Thanks!

 

[Astronuc]

According to the site you posted, Hh would have the disease, but HH would probably have a more severe form. So it appears that while Hh can survive to adulthood (IIRC - Woody and Arlo Guthrie), the HH would not. So Hh can survive to pass on the gene to another.

If the partner is hh, then Hh risk is 0.50. If parter is Hh, then risk of HH is 0.25 and risk of Hh is 0.5.

See also - http://en.wikipedia.org/wiki/Huntington's_Disease - but this is not under strict QC.

 

[Math Is Hard]

But the question remains: why does my professor state that only those with the HH genotype have Huntington's disease? She excludes Hh, and that does not make sense to me.

 

[Astronuc]

Well, from the literature on the internet, it would appear that your professor is incorrect.

A defective gene causes Huntington's disease. Only a single defective gene, inherited from either parent, is necessary to produce the disease. If one parent has a faulty gene, there is a 50 percent chance of the gene being passed on to children. Because symptoms do not appear until middle age, some parents may not even know that they are gene carriers until after they have children. Anyone inheriting the gene will eventually develop the disease. There is also a 50 percent chance that a child will not inherit the gene or develop the disease. Tests may now detect the gene for the disease before symptoms begin. This provides an opportunity for affected families to have informed genetic counseling.

University of Iowa - http://www.uihealthcare.com/topics/neurologicalhealth/neur3530.html

Huntington's disease is inherited as a single faulty gene on chromosome #4. There is a part of the gene that is repeated in multiple copies. The greater the number of repeats, the more likely it is that the person will develop symptoms and the greater the chance they will occur at a younger age. The disease may occur earlier and more severely in each succeeding affected generation because the number of repeats can increase.

National Institutes of Health - http://www.nlm.nih.gov/medlineplus/ency/article/000770.htm

The mode of inheritance of the disorder is "autosomal dominant" which means that the defective gene is located on one of the paired chromosomes (chromosome 4 in this case).

http://biology.wsc.ma.edu/biology/students/posters/caseit/10499m/Huntington/ - see bottom of page for more links to other sites.

 

[Math Is Hard]

Funny you should mention the Guthries, 'Nuc. I am going to post the exact question as given. Possibly there is some nuance in the wording that I have missed:

The allele for Huntington's Chorea is dominant. Woody Guthrie was heterozygous for this trait, and Mrs. Guthrie did not have Huntington's Chorea. What are the chances that their son Arlo will develop the symptoms?

I say: 50%

Prof says: 0%

 

[Astronuc]

Woody Guthrie is perhaps one of the most well-known (famous) people who died from Huntingdon's disease.

The Wikipedia bio says that his mother did have the disease, so presumably she is heterozygous -

He received various diagnoses (including alcoholism and schizophrenia), before he was finally discovered to be suffering from the Huntington's disease, the genetic disorder that had caused the death of his mother.

http://en.wikipedia.org/wiki/Woody_Guthrie

I am trying to remember is Arlo has it. He was very reluctanct to get the test for it - he just didn't want to know, and if he had it, then he likely would (or has) passed it along to his children.

A site devoted to Woody simply mentions that his mother was institutionalized - http://www.woodyguthrie.org/biography.htm


And this site that mentions he inherited HD from his mother -

Huntington's Disease was called "Huntington's Chorea" back when Woody Guthrie was diagnosed with it in 1952. He inherited the deadly degenerative brain disorder from his mother, who died from it at the age of 41...when Woody was 15 years old.

After a brave struggle, Woody Guthrie succumbed to Huntington's Disease on October 3rd, 1967.

Two of Woody's daughters have died of the disease as well.

http://www.songaweek.com/woody/songs/huntington.html

So somebody has got it wrong - Woody's mother either had it or she didn't.

 

[Hootenanny]

Funny you should mention the Guthries, 'Nuc. I am going to post the exact question as given. Possibly there is some nuance in the wording that I have missed:

The allele for Huntington's Chorea is dominant. Woody Guthrie was heterozygous for this trait, and Mrs. Guthrie did not have Huntington's Chorea. What are the chances that their son Arlo will develop the symptoms?

I say: 50%

Prof says: 0%

I would agree with you, if Woody was a heterozygote (Hh) and his spouse was homozygous recessive (hh) a simple monohybrid cross reveals that the genotype of any offspring have a 50% chance of being either heterozygous (Hh) or homozygous recessive (hh) and thus a 50% chance of the phenotypes being normal : HC patient. Perhaps, your proffessor meant to ask for the probability of the offspring having the more sevre case?

Reagrds,
-Hoot

 

[Math Is Hard]

Thanks. I am more and more convinced that my response is accurate, from reading things like this:

The allele for Huntington's is dominant, so only one copy is needed for the disease to occur.

http://www.emunix.emich.edu/~rwinning/genetics/beyond3.htm

and

Huntington's chorea is also a lethal dominant condition (HH = fatal) but homozygous dominant (Hh) people live to be ~40 or so, then their nervous system starts to degenerate. Woody Guthrie died of Huntington's.

http://www.biology.iupui.edu/biocourses/N100/2k4ch10mendelexcept.html

so I am going to have to go back to the prof and see what she meant.

Does anyone know how long someone who is homozygous dominant for Huntington's can live? I think I remember reading that embryonic death is common, and best case scenario, he/she will survive into early childhood.

 

[Astronuc]

Does anyone know how long someone who is homozygous dominant for Huntington's can live? I think I remember reading that embryonic death is common, and best case scenario, he/she will survive into early childhood.

It's apparently somewhat complicated because it depends on how many times the errent CAG sequence is repeated.

How Does It Persist?: Huntington's Disease as a Case Study in Population Genetics - http://www.hdac.org/features/article.php?p_articleNumber=22

We had a paradox, then: A disease gene that should be selected against persists in human populations at a relataively high frequency. The solution was arrived at once the nature of the gene as a trinucleotide repeat expansion was revealed. The gene for HD is maintained by a force that previously had been dismissed: Mutation. For the huntingtin gene, mutation from the normal to the disease gene does indeed occur at a higher frequency than the reverse. This is because expansion of the CAG repeat between generations is more likely to occur than contraction. As copies of the disease gene are being lost to negative selection, new copies are coming into the population by expansion of the CAG repeat from the normal into the disease range. It has been estimated that as many as 1% of persons with HD express such new mutations.

The CAG repetition was mentioned in one of the other links I posted.

So the professor may be thinking that Hh person will not get the disease, which may be the case if the person does not have the necessary number of CAG repeats.

See also - http://www.hdsa.org/site/PageServer