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Please observe the following pedigree of a family with a x-recessive disease (bleeder disease).

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The A's are genetic markers so close to the disease gene that recombination is negligible.

I understand it like this: They place markers that cut the DNA at the locus of the diseased gene. If you have the disease, your gene snip will be different in size than someone who does NOT have the disease and this will be visible on a gel. So if A1 is the disease marker, how come II:1 is not affected? He only has 1 X-chromosome and has the A1 marker?

EDIT: Another problem:

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Is the coming child affected? Here I don't understand how the mother A1,A1 is NOT affected when the child A1 is?! Obviously A1 is the diseased marker and the mother has two of them...So she should be sick? Unless it's spontaneous?

Am I misunderstanding something fundamentally?

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Genetic markers don't cut the DNA. They're simply regions of DNA sequence that happen to be variable between individuals (see my answer to your previous question). They might be measured using restriction enzymes (i.e. RFLP) to identify the exact difference, but it's not the marker that's cutting DNA. Furthermore, they don't necessarily cause disease. They're used in pedigree analysis to find regions that are linked with various phenotypes, among which is disease. However, linkage does not imply causation, especially with so few individuals.

To answer your first question II:1 isn't in the affected family - he married into it. In the affected family, A1 has become linked with the disease mutation. It is not necessarily linked with the disease in other families.

This is also the answer to your second question. I:2 has A1 marker on one chromosome associated with the disease allele, and one that's not. II:3 presumably inherited an X chromosome with the disease allele.

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  • $\begingroup$ So the unaffected individual who is married into the family has the same marker on the gene, called marker A1, in other words, if there's a sequence AGTAGTAGTAGT in the affected family and it is called marker A1, this means they have a disease, but he also has this sequence but not the disease because he doesn't have other traits the family members have? Am I finally understanding this right? (I'm really trying!) $\endgroup$ – Paze Jun 7 '15 at 0:48
  • $\begingroup$ Almost, but not quite. There is a marker A1 that has sequence AGTAGTAGTAGT where individuals with A2 with have sequence AGTAGTAAAAGT at the same A locus. Some very short distance away from the A locus, there is a disease locus - when individuals have only the m allele instead of the M allele, they have the disease. Because the A locus and the M locus are so close together (i.e. linked), meiotic recombination is very unlikely. So if the M locus becomes mutated on one chromosome that happens to have the A1 allele, the disease m allele becomes linked to the A1 allele + $\endgroup$ – blep Jun 7 '15 at 5:38
  • $\begingroup$ (cont'd) and you will see that the disease goes along with the A1 allele in successive generations. However, it could have just as easily been the M locus becoming mutated on a chromosome that has the A2 allele - and in some other families, this might be true for the same disease. In that case, the disease will be associated with the A2 allele for that family, for the very same disease. The marker allele is only informative within the context of a single pedigree - you don't know which allele is associated for unrelated families. What you do know is that the marker is linked to the disease + $\endgroup$ – blep Jun 7 '15 at 5:41
  • $\begingroup$ (cont'd) because the two loci are so close by -- it could just be a different allele in different families. Does that make sense? $\endgroup$ – blep Jun 7 '15 at 5:42
  • $\begingroup$ It all makes sense and I'm drawing it up right now but it would help if you clarified what you mean by "m" and "M" allele as it is the only thing confusing me and I need that information to read the rest of the answer. $\endgroup$ – Paze Jun 7 '15 at 13:00

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