Genetics: understand variation and inheritance
Genetics studies variations in DNA (the genetic code) and how traits are passed through generations. A person’s health is also influenced by their environment and/or other factors. Begin by distinguishing between the genetics of interest in a problem and the specific question(s) posed.
Put each term at the right scale
Genetic information is contained in DNA. Regions of DNA with biologic significance are referred to as genes. Chromosomes are large units consisting of long DNA molecules wrapped around associated proteins. Genes may include coding regions for proteins while others encode for functional RNAs. The terms gene, chromosome and genome are NOT interchangeable.
An illustration of the organization of these concepts will help clarify the relationship among them. Identify a portion of a DNA molecule, and show this portion as part of a chromosome. Your drawing should illustrate organization, but does not have to demonstrate all features. Before you begin interpreting a report, determine if it refers to a mutation in one gene, a series of genes or a complete chromosome.
A change in sequence needs interpretation
People differ in their DNA sequences. These genetic variations are referred to as "variants," and simply having a variant does not automatically indicate disease. Many variants appear to have no impact on biology; however, those that cause an alteration in the normal functioning of a biological process can increase the likelihood that an individual may develop a medical condition. Identifying a variant is the first step toward understanding its implications. However, determining the implications of a variant requires additional evidence beyond the designation "variant."
A DNA change may be inherited or arise during life. In addition to the potential for heritability, a DNA change has different inheritance implications in a gamete (egg or sperm) and a somatic cell. Additionally, individuals may acquire a novel variant and still lack an identified family history of disease. Therefore, prior to attempting to evaluate a finding, avoid assuming that there must be multiple generations of affected relatives.
Use family patterns with care
There are many single-gene conditions that follow recognizable family patterns such as dominant, recessive or X-linked (sex-chromosome). Dominant and recessive describe how copies of a gene contribute to the particular condition. Neither term implies strength nor weakness. There are many conditions caused by multiple genes; environmental factors; or chromosomal abnormalities. These types of conditions do not always fit into a simple single-gene model. The most suitable model will depend on the nature of the condition under study.
Prior to selecting a family pattern for use in constructing a teaching pedigree, consider the relationships demonstrated by the pedigree and the information provided. Do not fill-in omitted information based solely on assumptions. Pedigrees can serve as evidence but cannot independently diagnose an individual or assess an individual's reproductive risk. Assessments of both require consideration of that which remains unknown.
Match the test to the question
Genetic testing has many goals including investigating suspected conditions; establishing carrier status; or estimating certain inherited risks. Genetic tests also vary significantly with regard to the number and length of DNA segments that they evaluate. As a result, the findings of one type of test cannot definitively answer all questions regarding genetics. Consider the reasons for conducting the test; the source of the sample tested; and the types of findings produced by the methods used.
A negative result from a test does not eliminate all possible genetic explanations for the suspected condition. The identification of a variant via testing does not necessarily equate to an established diagnosis or increased risk to reproductive health. Genetic counseling provides education related to the intent behind a test; possible outcomes from testing; and interpretations related to those findings. Decisions concerning an individual or family need a clinical assessment of the complete situation.
Check your understanding
A short quiz, with an explanation after each answer.
Does the term variant automatically mean that a DNA difference causes disease?
When revising a teaching case, document the structural relationship between components in addition to documenting the observation (finding), as well as addressing what specifically is being questioned. Also, use the quiz to verify that you distinguish between observed family patterns and conclusions related to inheritance before expanding on details.