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Genetics Unit 5: Pedigrees and Human Genetics

Humans cannot be crossed experimentally, so geneticists read family pedigrees to find modes of inheritance and calculate the risk to future children.

Covers: Pedigree symbols and terms, Autosomal recessive and dominant patterns, X-linked, Y-linked and mitochondrial patterns, Genetic risk calculation, Consanguinity and inbreeding, Imprinting and uniparental disomy, Genetic testing, screening and twin studies

Study guide

A pedigree is a family tree using standard symbols: squares for males, circles for females, filled symbols for affected people, horizontal lines for matings and vertical lines down to children. Generations are labeled with Roman numerals, and the proband who brought the family to attention is often marked with an arrow. Reading a pedigree means testing each mode of inheritance against the data and ruling out any mode that would require an impossible event. Rare traits are usually assumed to enter a family only once, so people marrying in are assumed not to carry the allele unless stated.

Autosomal recessive traits often skip generations, affect both sexes equally, and appear in children of unaffected carrier parents, especially in consanguineous matings. Autosomal dominant traits appear in every generation, every affected person usually has an affected parent, and both sexes pass the trait, including father to son. X-linked recessive traits mostly affect males, pass from affected men through carrier daughters to grandsons, and never go father to son; an affected woman must have an affected father and all affected sons. X-linked dominant traits pass from an affected father to all daughters and no sons. Y-linked traits pass father to all sons, and mitochondrial traits pass from mothers to all children.

Risk calculation uses the probability rules from Unit 1. The key fact is that an unaffected child of two carriers has a 2/3 chance, not 1/2, of being a carrier, because the aa class has been excluded. For an unrelated partner, use the population carrier frequency. Multiply each parent's carrier probability by the chance two carriers have an affected child (1/4). When new information arrives, such as unaffected children or a parent who stays unaffected despite incomplete penetrance, update the carrier probability with conditional probability (Bayes' rule): weight each possibility by how likely it makes the observed data.

Some human patterns break the simple rules. Genomic imprinting makes expression depend on the parent of origin: deletion of a chromosome 15 region from the father gives Prader-Willi syndrome, and from the mother gives Angelman syndrome. Uniparental disomy, in which both homologs come from one parent, can cause imprinting disorders or make a child homozygous for one parent's recessive allele. Consanguinity raises the risk of recessive disorders because relatives may share an allele identical by descent; the inbreeding coefficient for a child of first cousins is 1/16.

Genetic testing applies these ideas. Carrier screening identifies heterozygotes in couples or at-risk populations. Prenatal diagnosis tests fetal cells from chorionic villus sampling or amniocentesis, and noninvasive prenatal screening examines fetal DNA fragments in maternal blood. Newborn screening looks for treatable conditions like PKU, where early diet prevents brain damage. For complex traits, twin studies compare identical and fraternal twins; higher identical-twin concordance suggests genetic influence, and Falconer's formula H² = 2(r_MZ − r_DZ) estimates heritability in that population.

Key ideas

• Rule out modes of inheritance that would require impossible transmissions.
• Father-to-son transmission rules out X-linked inheritance.
• An affected daughter of an unaffected father rules out X-linked recessive inheritance.
• Unaffected siblings of an affected child of carriers have a 2/3 carrier risk.
• Risk = parent 1 carrier probability × parent 2 carrier probability × 1/4.
• Conditional probability updates carrier risk when unaffected children or relatives are observed.
• Imprinting and uniparental disomy create parent-of-origin effects.

Formulas and rules

Common mistakes

• Using 1/2 instead of 2/3 for the carrier risk of an unaffected sibling.
• Using 1/4 per child when one parent is affected (aa); the correct factor is 1/2 for a carrier partner.
• Calling a trait X-linked recessive when an affected daughter has an unaffected father.
• Confusing mitochondrial inheritance (all children of affected mothers) with X-linked dominant.
• Multiplying a parental carrier risk separately for every child instead of conditioning once.

Before the test, make sure you can

• Read pedigree symbols and identify the proband and generations.
• Determine the mode of inheritance and justify what rules out the others.
• Calculate carrier and recurrence risks, including the 2/3 rule.
• Update carrier risks with conditional probability.
• Explain imprinting with Prader-Willi and Angelman syndromes.
• Explain how consanguinity increases recessive disease risk.
• Describe carrier, prenatal and newborn screening and their uses.
• Interpret twin concordance and estimate heritability.

Words to know

Pedigree

A diagram of a family's relationships and phenotypes across generations.

Proband

The affected individual who brings the family to medical attention.

Consanguineous mating

A mating between related individuals, shown with a double line.

Autosomal recessive pattern

Skips generations, affects both sexes, and affected children usually have carrier parents.

Autosomal dominant pattern

Appears in every generation, with father-to-son transmission possible.

X-linked recessive pattern

Mostly affects males, passes through carrier females, never father to son.

X-linked dominant pattern

Affected fathers pass the trait to all daughters and no sons.

Mitochondrial inheritance

Traits pass from mothers to all their children, never from fathers.

Identical by descent

Two alleles that are copies of the same ancestral allele.

Inbreeding coefficient (F)

The probability that two alleles at a locus are identical by descent.

Genomic imprinting

Gene expression that depends on whether the allele came from the mother or father.

Uniparental disomy

Both homologs of a chromosome inherited from one parent.

Carrier screening

Testing to find heterozygotes for a recessive disorder.

Amniocentesis

Sampling amniotic fluid to obtain fetal cells for testing.

Concordance

The percentage of twin pairs in which both twins show a trait.

Heritability

The proportion of phenotypic variation in a population due to genetic variation.

Sample practice questions

30 more questions like these, from level 1 to 5, are in the practice set.