Expert: Dana Krempels, Ph.D. - 9/21/2008

Question
QUESTION: Hi Dana, my questions are about some autosomal disorders.
First of all, I can't understand why do autosomal genetic disorders exist. From the book, autosomal disorders should be quite common cause
1) between a heterozygous affected person and a homozygous unaffected would produce 75% affected, and rest of the combination all produces 100% affected(except a pair of homozygous recessive).
Somehow, I thought that autosomal chromosome are suppose to the 22 pairs of chromosome except the one that determines sex, if I'm right, then all disorders on it should be inherited rather than in the above case 75%.
Could you explain why and give me some examples of this type of disorder?

After that, could you explain to me what is the difference between autosomal recessive and autosomal dominant? I saw these disorders on Princeton Review, but I have no idea what is it.

Finally, could you also explain the difference between X-linked dominant and recessive disorder?

ANSWER: Dear Angela,

I think the main reason you're confused about this phenomenon is that you are not clear on the definitions of dominant and recessive alleles of a particular gene.  Let's clear that up first.

A gene can exist in several different forms called alleles.  (Think of the gene as "ice cream" and the alleles as "chocolate, vanilla, coffee, pistachio" or whatever).  Every person inherits one copy of a gene from each parent, and so has only two alleles, even if more than two alleles exist for that gene.

A *dominant* allele is one that masks the expression of a *recessive* allele.  For example, in humans the allele coding for a little "Widow's Peak" (a pointy bit of hair coming down onto the forehead) is dominant
to the allele coding for a straight hairline across the forehead.  We'll call the Widow's Peak allele (W) and the straight hairline allele (w).

A person who inherits two copies of W (genotype WW) will have a Widow's peak, as will a person who inherits one copy of each of the alleles (genotype Ww), because W masks the expression of w.  A person who has the genotype ww will have a straight hairline.

Now, back to the autosomal genetic disorders.  An autosomal gene is one that occurs on one of the 22 pairs of autosomes (i.e., the chromosomes that are not the X and/or Y chromosomes that are involved in sex determintion).  That's all that "autosomal" means.

If an autosomal genetic disorder is *dominant* (X), only then will you get the 75% expression in the cross you describe.  If the condition is recessive (x), then a cross between a heterozygote (Xx) and a homozygote (XX; unaffected) will give 100% unaffected offspring, 50% of whom will be carriers of the condition.

I hope this helps explain the situation more clearly.

An X-linked gene is one that is located on the X chromosome.  And just as with an autosomal trait, the dominant version will *mask* the expression of the recessive one.  This can get very complicated, so if you need more information on how X-linked traits are inherited differently by males and females (mammals), then please see my Gentics notes here:

http://www.bio.miami.edu/dana/250/25008_5.html

I hope that will help!

Good luck!

Dana


---------- FOLLOW-UP ----------

QUESTION: Hi, Dana. Thanks for the detailed explanation, however, I'm still confused about a couple of things.
1) How will a recessive disorder come up?
Dominant ones show up because the affected person is either homozygous affected or heterozygous, so what is the genotype of the recessive disorders?
2) Could you explain the difference between each? I mean like, if I have an unknown disorder occurring in a family, with given data, ask to determine the type of genetic disorder

P.s Do you know any site that provide exercises for this kind of genetic question? Say, the question gives statistical data and asks you to figure out whether the disorder is autosomal or X-linked, dominant or recessive?

Answer
Dear Angela,

1) How will a recessive disorder come up?
Dominant ones show up because the affected person is either homozygous affected or heterozygous, so what is the genotype of the recessive disorders?

For a recessive disorder to be expressed, the individual must have two copies of the recessive, faulty gene.  In other words, if the gene for Tay Sachs disease has two alleles, normal (T) and faulty (t), then a person will not express Tay Sachs disease if s/he has the genotype TT (homozygous dominant) or Tt (heterozygous).  For expression of the disorder to occur, the genotype must be tt (homozygous recessive).

2) Could you explain the difference between each? I mean like, if I have an unknown disorder occurring in a family, with given data, ask to determine the type of genetic disorder?

Difference betweeen each what?  Dominant and recessive?  I think I already did that in my previous answer, and you can also read the lecture notes for which I sent the link for more explanation.

P.s Do you know any site that provide exercises for this kind of genetic question? Say, the question gives statistical data and asks you to figure out whether the disorder is autosomal or X-linked, dominant or recessive?

Most genetics textbooks will have such exercises and problems.  I'm not sure how in depth practice problem web sites will be, but here are a few:

http://biology.clc.uc.edu/courses/bio105/geneprob.htm

http://www.ksu.edu/biology/pob/genetics/intro.htm

http://www.biology.arizona.edu/Mendelian_genetics/mendelian_genetics.html

Hope that helps!

Dana