The diagram to the right shows the co-segregation or co-inheritance of a tetranucleotide polymorphism (here called a 'microsatellite' which is short for 'microsatellite polymorphic marker') and a disease phenotype in a family. The line drawing depicts the family pedigree (refer to the section on how to draw your pedigree). Males are depicted as squares, females as circles, affected individuals are red and unaffected individuals are black. In this family, an affected man has five children of whom the third and fifth are affected. The fifth child has a daughter who is also affected. All family members and the unaffected parents participated in the study. Each individual's DNA was radioactively amplified by PCR using primers to a specific STR and then loaded into the lane on the gel under their specific symbol in the pedigree.
The first step in interpreting this data is to determine if the polymorphism is inherited in a Mendelian fashion. Each individual has two bands or 'alleles' in their lane, one inherited from their father and one from their mother. The alleles are numbered 2 through 6 in ascending order from the bottom of the gel. The first individual, the father of the five children, has alleles 2 and 5. The second individual, the mother of the five children, has alleles 3 and 6. Therefore, Mendelian genetics would lead us to expect that each child has alleles 2-3, 2-6, 5-3, or 5-6. And looking at the children, this is what they have (2-6, 2-3, 5-6, 2-3, and 5-3). The last daughter, who has alleles 5-3, has a husband with alleles 3-4. Their child is a 5-4. So the family does show inheritance of this polymorphism consistent with Mendelian genetics. Next, look at the relationship between the allele size and affection status. The father is affected and has alleles 5-2. He passes his allele 5 on to both affected daughters, and his allele 2 on to the three unaffected children. The affected daughter, who is a 5-3, again passes the 5 allele on to her affected daughter. Therefore, allele 5 of this marker is co-inherited, or co-segregates with the disease phenotype. If the family were larger and this pattern continued, the analysis would generate a lod score consistent with linkage.
Family size and stucture, the number of family members who agree to participate in the linkage study, and accuracy of clinical data from each participant all play a major role in the success of linkage analysis. To obtain a significant LOD score, it is necessary to have a minimal number of family members participating in the study. In addition, for the analysis to be successful, it is also necessary to have accurate clinical information about each participant.
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