12.5: Pedigree Analysis

A pedigree is a diagram displaying a family’s history of a trait. Analyzing pedigrees can reveal (1) whether a trait is dominant or recessive, (2) the type of chromosome, autosomal or sex, a trait is linked to, (3) genotypes of family members, and (4) probabilities of phenotypes in future generations. For families with a history of autosomal or sex-linked diseases, this information can be crucial to family planning.

Pedigrees Display Family Histories

In various plant and animal species, scientists study the inheritance of phenotypes, or traits, using carefully controlled mating experiments called crosses. For example, monohybrid crosses can establish trait dominance or recessiveness, and test crosses can determine the genotype (homozygous or heterozygous) of an organism exhibiting a known dominant phenotype.

Humans, however, cannot be ethically or feasibly crossed. Therefore, researchers analyze pedigrees, or family trees, to understand how human traits and diseases are inherited. Pedigrees display a family’s history of a trait across generations and family members. Using the same principles that apply to crosses to analyze reproductive events that have already occurred, information about trait heritability can be inferred.

Rows of a Pedigree Represent Generations of a Family

On a typical pedigree, squares represent males and circles represent females. Shaded squares or circles signify the presence of a trait of interest. Rows are generations, sometimes labeled with Roman numerals. The oldest generation comprises the top row, with each subsequent generation on separate rows. Within each generation, or row, family members may be labeled numerically from left to right and referred to by their generation and position. For instance, the second individual in the first generation is I-2.

A horizontal line connecting two parents is called a marriage line, although marriage is not necessarily involved. A vertical line of descent extending downward from a marriage line connects to a horizontal sibling line. Individuals connected to the line of descent via the sibling line are offspring. Individuals that are not directly connected to the sibling line entered the family via marriage lines, and are not biological offspring of the preceding generation.

Pedigrees Reveal Information about Trait and Disease Inheritance

Dominant traits are distributed differently than recessive traits. Inheritance is also distinct for traits determined by genes on sex chromosomes compared to traits linked to autosomes (non-sex chromosomes). By examining a trait’s presence and absence throughout a family’s history, pedigree analysis can provide information about trait inheritance. Although many diseases are influenced by multiple genes, several display Mendelian inheritance patterns. For these conditions, pedigrees can give important clues about the risk of disease inheritance and propagation.

Traits caused by genes on autosomes and requiring two allele copies to influence a phenotype are autosomal recessive. Several disorders are autosomal recessive, including cystic fibrosis, Tay-Sachs disease, and maple syrup urine disease. Most people with these diseases have heterozygous parents who do not have the condition but carry a causal allele.

These carriers can unknowingly impart the disease to their children, which partially explains why autosomal recessive diseases are more common than their dominant counterparts. Comparing generations on a pedigree can reveal whether an autosomal trait is dominant or recessive. Neither parent has the trait, but one child inherits it. Thus, it must be recessive.

Freckles and polydactylism (extra fingers or toes) are autosomal dominant traits in humans, requiring only one copy of the determining allele to influence phenotype. Autosomal dominant diseases, such as Huntington’s disease, afflict ~50% of offspring with one affected parent. Many of these diseases do not cause symptoms until later in life, after reproductive age. Children can inherit these diseases from unknowingly affected parents, highlighting the importance of analyzing family history. Although both parents exhibit the trait, one of their children does not. Since a cross between two recessive parents consistently produces a recessive phenotype, this trait must be dominant.

Traits Can Be Autosomal or Sex-linked

In addition to 44 autosomes, humans have two sex chromosomes, which are homologous in females (XX), but non-homologous in males (XY). Traits determined by sex chromosomes are sex-linked. Most sex-linked traits in humans are X-linked recessive. Only males can inherit Y-linked traits because females lack a Y chromosome. Additionally, the X chromosome contains ~800-900 protein-coding genes compared to ~70-80 on the Y chromosome.

X-linked traits include hemophilia, muscular dystrophy, and red-green color blindness. Since males have only one X chromosome, they are hemizygous (rather than homozygous or heterozygous) for an X-linked trait. Males are more susceptible to recessive X-linked traits than females because they have no second allele to potentially mask a causal recessive allele.

To understand how traits or disorders are inherited in humans, scientists analyze family trees also known as pedigrees.

In a typical pedigree, squares denote males, circles indicate females and a horizontal line between these shapes represents a mating.

If such a union produces children, a perpendicular line is drawn down from the parents towards any sons and daughters.

Thus progressively lower rows in the pedigree represent subsequent generations in a family.

For individuals that demonstrate a disease phenotype, like the skin rashes associated with biotinidase deficiency disorder where a person lacks the enzyme necessary to obtain vitamin B7, their associated shapes in the pedigree are shaded in.

By assessing which family members have been diagnosed with biotinidase deficiency, researchers can determine whether this disease results from a recessive or dominant mutation in a single gene, situated on an autosome or sex chromosome.

Here females and males are stricken at the same rate. Unafflicted parents have children with the disorder and not every generation contains a family member with the disease, a pattern that suggests biotinidase deficiency is autosomal recessive.

Importantly pedigree analysis not only elucidates inheritance patterns, but can also help couples understand their risk of having a child with the disorder given their family history.