4.3: Pedigrees

Learning Objectives

• Draw a pedigree based on information in a story problem.
• Using pedigrees, distinguish between dominant and recessive autosomal inheritance.

 

When working with plants, animals, or humans, pedigrees can be used to follow traits among family groups.

Pedigrees are diagrams that show the phenotypes and/or genotypes for a particular organism and its ancestors. While commonly used in human families to track genetic diseases, they can be used for any species and any inherited trait. These diagrams are used to determine the mode of inheritance of a particular disease or trait, and to predict the probability of its appearance among offspring. Pedigree analysis is therefore an important tool in both basic research and genetic counseling. Historically, a standardized set of symbols has been used to represent an individual’s sex (circle for female, square for male), family relationships (lines between individuals) and phenotype (unfilled or filled symbol). Matings that represent a union of gametes (not necessarily marriage or other relationships) are drawn as a line joining a two symbols, while a consanguineous mating (a mating between closely related individuals) is two lines.

A modern understanding of assisted reproduction, complex family relationships, disorders of sex determination (DSD), and gender identity requires us to consider inclusive symbols and notations. When gender is unknown, convention has dictated that a diamond be used. The diamond has also been suggested as substitute symbol to indicate a transgender or non-binary individual. However, there is not yet an official standard for indicating trans or non-binary persons; a recent survey of genetic counselors presents several alternatives (Sheehan et al., 2020). These possibilities including a square with a circle inside for a trans male or circle with a square inside for a trans female, the appropriate symbol for the persons gender identify with text or abbreviations can be used to provide additional information, for example trans male, trans female, FTM (female to male), or FTNB (female to non-binary). A circle or square symbol with the gender identify could be used with the sex chromosomes indicated could also be used. Updates and standardization of these symbols are likely to continue to occur. Other circumstances that might need to be noted are assisted reproduction, including sperm or egg donors as well as surrogates, as these may include individuals who contribute genes to the offspring, but may not have a role in the family or family group.

 

Figure \(\PageIndex{1}\): Left: Traditional symbols used in drawing a pedigree are circles for females and squares for males (Copyright: Original-Deyholos-CC:AN). Right: Possible approaches for depicting trans people in pedigree charts compiled from a survey of genetic counseling professionals (Sheehan et al., 2019) as well as non-official proposals to present diversity in biology classes (Hale, 2020).

 

Figure \(\PageIndex{2}\): Left: Example pedigree in which an unaffected male and female have three offspring, one female to non-binary, one female, and one male who is affected with a disease or phenotype. Right: Example designation of egg or sperm donors as a symbol with a D for donor connected by a diagonal line to the offspring.

Each pedigree represents all of the available information about the inheritance of a single trait (most often a disease) within a family. If an individual is known to have symptoms of the disease or trait (affected), the symbol is filled in. Sometimes a half-filled in symbol is used to indicate a known carrier of a disease; carriers are unaffected but can pass an allele to subsequent generations because they are heterozygous. Note that when a pedigree is constructed, it is often unknown whether a particular individual is a carrier or not, so carriers are not always explicitly indicated in a pedigree. Unless additional information is provided, assume that the pedigrees presented in this section are accurate, and represent fully penetrant traits.

The pedigree is drawn using factual information, but there is always some possibility of errors in this information, especially when relying on family members’ recollections or even clinical diagnoses. In real pedigrees, further complications can arise due to incomplete penetrance (including age of onset) and variable expressivity of disease alleles. A pedigree may be drawn when trying to determine the nature of a newly discovered disease, or when an individual with a family history of a disease wants to know the probability of passing the disease on to their children.

References

Bennett, R.L., French, K.S., Resta, R.G. and Doyle, D.L. (2008), Standardized Human Pedigree Nomenclature: Update and Assessment of the Recommendations of the National Society of Genetic Counselors. J Genet Counsel, 17: 424-433. https://doi.org/10.1007/s10897-008-9169-9

Hales KG. Signaling Inclusivity in Undergraduate Biology Courses through Deliberate Framing of Genetics Topics Relevant to Gender Identity, Disability, and Race. CBE Life Sci Educ. 2020 Jun;19(2):es2. doi: 10.1187/cbe.19-08-0156. PMID: 32357097.

Sheehan E, Bennett RL, Harris M, Chan-Smutko G. Assessing transgender and gender non-conforming pedigree nomenclature in current genetic counselors' practice: The case for geometric inclusivity. J Genet Couns. 2020 Dec;29(6):1114-1125. doi: 10.1002/jgc4.1256. Epub 2020 Mar 30. PMID: 32232917.

 

 

Using pedigrees to visualize patterns of inheritance

Given a pedigree of an uncharacterized disease or trait, one of the first tasks is to determine which modes of inheritance are possible and then which mode of inheritance is most likely. This information is essential in calculating the probability that the trait will be inherited in any future offspring.

Important to remember about autosomes & allosomes (sex chromosomes)

• Remember that in humans the autosomes are the same in both sexes. Both sperm and oocytes contain one copy of each autosome.
• Remember that sex chromosomes may differ between individuals of different sexes. Both sperm and oocytes normally contain one copy of a sex chromosome. In oocytes this chromosome is almost always an X; in sperm, it could be X or Y.

Autosomal Dominant Inheritance

When a disease is caused by a dominant allele of a gene, every person with that allele will show symptoms of the disease (assuming complete penetrance), and only one disease allele needs to be inherited for an individual to be affected. Thus, every affected individual must have an affected parent and the trait often appears in every generation; this pattern is often called a vertical inheritance pattern, as in from top to bottom of the pedigree. A pedigree with affected individuals in every generation is typical of autosomal dominant diseases. However, beware that other modes of inheritance can also show the disease in every generation, as described below. It is also possible for an affected individual with an autosomal dominant disease to have a family without any affected children, if the affected parent is a heterozygote. This is particularly true in small families, where the probability of every child inheriting the normal, rather than disease allele is not extremely small. Note that autosomal domintant diseases are usually rare in populations, therefore affected individuals with autosomal dominant diseases tend to be heterozygotes (otherwise, both parents would have had to been affected with the same rare disease). Achondroplastic dwarfism, and polydactyly are both examples of human conditions that may follow an autosomal dominant mode of inheritance.

Figure \(\PageIndex{3}\): A pedigree consistent with autosomal dominant inheritance. (Original-Deyholos-CC:AN)

Autosomal Recessive Inheritance

Diseases that are inherited in an autosomal recessive pattern require that both parents of an affected individual carry at least one copy of the disease allele. With autosomal recessive traits, many individuals in a pedigree can be carriers, probably without knowing it. Compared to pedigrees of dominant traits, autosomal recessive pedigrees tend to show fewer affected individuals and are often described as "skipping" generations. Thus, the major feature that distinguishes autosomal recessive from dominantly inherited traits is that unaffected individuals can have affected offspring.

Figure \(\PageIndex{4}\): A pedigree consistent with autosomal recessive inheritance. (Original-Deyholos_CC:AN)

 

Contributors and Attributions

• Dr. Todd Nickle and Isabelle Barrette-Ng (Mount Royal University) The content on this page is licensed under CC SA 3.0 licensing guidelines.