Individual Genetic Variation

Differences in alleles can be scored via laboratory testing. The ability to score allele differences accurately within families, between families, and between laboratories is critically important for linkage analysis in both simple Mendelian and genetically complex common disorders. Linkage analysis traces coinheritance of a disease gene and polymorphic markers such as SNPs to discover where in the chromosomes the disease gene is located.

Allele scoring strategies may be as simple as noting the presence (+) or absence (−) of a deletion or point mutation, or as complicated as assessing the allele size in base pairs of DNA. The latter application is common when highly polymorphic; microsatellite repeat markers are used in linkage analysis.

When genetic counselors talk to patients and families about mutations (a type of genetic variation) that are present in themselves or their children, they are careful to point out that each individual is estimated to carry between five to seven deleterious alleles that, in the right combination with other genes or with specific environmental influences, can lead to disease. Most of us do not know which deleterious genes we carry. Some are recessive and do not influence the genotype unless paired with a second recessive allele. Thus, these alleles will not be noticed without genetic analysis. And, genetic counselors are careful to avoid the term "mutation," because it is potentially stigmatizing. When speaking with patients, they prefer to use the more neutral term "variant."