Complications In Linkage Disequilibrium And Genetic Maps In General

The human genome is a potential minefield of uncharted genetic events, hidden rearrangements, new mutations, and genetic heterogeneity. Failure to see linkage disequilibrium near a gene does not mean that the gene is far away. Two of the most plausible potential complications are the existence of more than one founder or the existence of a significant fraction of alleles in the population that have arisen by new mutations. For example, in the case of dominant lethal diseases (those in which, nominally, the affected individuals have no offspring), one must expect that most disease alleles will be new mutations. Multiple founders can occur in distinct geographical populations, and they can be tested for by subdividing the linkage disequilibrium analysis accordingly. However, our increasingly mobile population, at least in developed countries, will make such analyses increasingly difficult.

Two other reasonable explanations for a failure to see linkage disequilibrium near a disease gene of interest are shown in Figure 6.27. The first of these is the possible presence of recombination hot spots. If the recombination pattern in the region of interest is punctate, then an even gradient of linkage disequilibrium will not be seen. Instead, markers that lie within a pair of hot spots will appear to be in disequilibrium, while those that lie on opposite sides of a hot spot will appear to have equilibrated. The occurrence of any disequilibrium in the region is presumptive evidence that a disease gene is there, since this is the basis for selection of the particular set of individuals to be examined. However, the complex pattern of allele statistics in the region will make it difficult to narrow in on the location of the disease gene.

Figure 6.27 complications that can obscure evidence for linkage disequilibrium. (a) Recombination hotspots near the disease gene. (b) Mutation hot spots near the disease gene.

A second potential source of confusion is the presence of mutation hotspots. These are quite common in the human genome. For example, the sequence CpG is quite mutagenic in those regions of the genome where the C is methylated, as discussed in Chapter 1. When mutation hotspots are present, these alleles appear to have equilibrated with their neighbors, while more distant pairs of alleles may still show deviations from equilibrium. As in the case of recombination hotspots, disequilibrium indicates that one has not sampled the population randomly. This is presumptive evidence for a disease gene nearby, but mutation hotspots weaken the power of the disequilibrium approach to actually focus in on the location of the desired gene.

Natural Vertigo And Dizziness Relief

Natural Vertigo And Dizziness Relief

Are you sick of feeling like the whole world Is spinning out of control. Do You Feel Weak Helpless Nauseous? Are You Scared to Move More Than a Few Inches From The Safety of Your Bed! Then you really need to read this page. You see, I know exactly what you are going through right now, believe me, I understand because I have been there & experienced vertigo at it's worst!

Get My Free Ebook


Post a comment