Pedigree chart examples: inheritance patterns worked through

Short version. Reading a pedigree is a structured exercise: (1) identify the proband; (2) trace affected individuals through the generations; (3) ask whether transmission is vertical (every generation), horizontal (a single sibship), or sex-biased; (4) test each candidate pattern against the observed data; (5) rule out alternatives. The five worked examples below illustrate the hallmark features of each common Mendelian inheritance pattern, with the decision logic spelled out step by step.

The examples are schematic — real clinical pedigrees routinely show reduced penetrance, variable expressivity, and incomplete information that complicate pattern recognition. Treat these as training aids; in clinic, a pedigree narrows the differential and tells you which tests to order, but a definitive diagnosis usually requires molecular confirmation.

Example 1: Autosomal dominant inheritance

A three-generation family with a condition appearing in every generation. The proband's mother, maternal grandfather, and one maternal aunt are also affected. The grandfather has a brother who is also affected and who has two affected daughters.

                 I-1            I-2
                  ■───────────────○
                           │
        ┌───────────┬──────┴──────┬──────────┐
      II-1         II-2          II-3       II-4
       ■            ●             □          ○
       (affected   (affected)    (unaff.)   (unaff.)
        uncle)        │             │
                      │             │
              ┌───────┼───────┐     │
            III-1   III-2   III-3   (no children shown)
             ■ ←   ○        ■
           PROBAND

Decision rationale.

1. Identify the proband. III-1, marked with the arrow.
2. Trace affected individuals. Affected in every generation: I-1 (grandfather), II-1 and II-2 (uncle and mother), III-1 and III-3 (proband and brother). Vertical transmission.
3. Assess sex distribution. Both males and females affected, in roughly equal numbers. Not obviously sex-biased.
4. Check for male-to-male transmission. I-1 (male, affected) transmits to II-1 (male, affected). This excludes X-linked inheritance, because a father does not pass his X chromosome to his sons.
5. Assess fraction affected. Roughly half the offspring of each affected parent are affected (II-2's children: 2 of 3 affected; I-1's children: 2 of 4 affected) — consistent with autosomal dominant (50% expected transmission from an affected heterozygote).
6. Conclusion. Pattern consistent with autosomal dominant. Examples include Huntington disease, neurofibromatosis type 1, Marfan syndrome, familial hypercholesterolaemia, and many hereditary cancer predispositions (BRCA1/2-associated, Lynch syndrome).

Example 2: Autosomal recessive inheritance (with consanguinity)

A three-generation family in which a sibship in the third generation contains two affected individuals. Their parents are first cousins. No affected individuals appear in any other branch of the family.

      I-1          I-2         I-3          I-4
       □────────────○           □────────────○
            │                         │
     ┌──────┴──────┐            ┌─────┴──────┐
    II-1          II-2         II-3         II-4
     □             ●           □─────────────● (1st cousin
   (unaff.)      carrier      carrier         carriers)
                   │ ═════════════ │
                   │ (consanguineous)
                   │
             ┌─────┼─────┬─────┐
           III-1 III-2 III-3 III-4
            ○     ■     □     ● ←
          unaff.  aff.  unaff. PROBAND (aff.)

Decision rationale.

1. Identify the proband. III-4, marked with the arrow.
2. Trace affected individuals. Affected in one generation only (III-2 and III-4), clustered within a single sibship. Horizontal clustering.
3. Assess parental status. Both parents are unaffected. Affected children of unaffected parents strongly suggests recessive inheritance (both parents are obligate heterozygous carriers).
4. Note consanguinity. The double horizontal line between II-2 and II-3 indicates a first-cousin union. Consanguinity raises the prior probability of autosomal recessive disease because it increases the chance that both parents inherited the same variant identical by descent from a common ancestor.
5. Check sex distribution. One affected male and one affected female in the sibship — no sex bias.
6. Conclusion. Pattern consistent with autosomal recessive. Examples include cystic fibrosis, sickle cell disease, phenylketonuria, Tay-Sachs disease, and the autosomal recessive ataxias.

In Evagene, consanguinity is marked with the double horizontal line and Wright's coefficient of inbreeding (F) is computed automatically — for first-cousin offspring F = 1/16, raising the expected frequency of rare recessive homozygous states appreciably.

Example 3: X-linked recessive inheritance (haemophilia-style)

The classical haemophilia pedigree: affected males across generations, inherited through unaffected female carriers. Queen Victoria's descendants are the canonical historical example.

          I-1                I-2
           □─────────────────●  (carrier)
                    │
    ┌────────┬──────┴──────┬─────────┐
   II-1    II-2          II-3      II-4
    ■       ●             □         ●
  (affected) (carrier)   (unaff.)  (carrier)
             │                        │
     ┌───────┴────┐              ┌────┴─────┐
   III-1        III-2          III-3      III-4
    □            ■ ←             ●          □
  (unaff.)    PROBAND         (carrier)   (unaff.)
             (affected)

Decision rationale.

1. Proband. III-2, affected male.
2. Sex distribution of affected individuals. Affected individuals are overwhelmingly male (II-1 and III-2). Female relatives are unaffected but many are obligate carriers (I-2, II-2, II-4, III-3).
3. Transmission. The condition skips generations on the female side but reappears in male descendants through female carriers. Affected males inherit from carrier mothers, never from affected fathers (no male-to-male transmission).
4. Test for male-to-male transmission. None present. Compatible with X-linked recessive.
5. Carrier inference. I-2 must be a carrier (she has an affected son and is unaffected herself). II-2 and II-4 (daughters of I-2) each have a 50% carrier probability a priori; II-2 is confirmed because she has an affected son.
6. Conclusion. Pattern consistent with X-linked recessive. Examples include haemophilia A and B, Duchenne muscular dystrophy, red-green colour blindness, and G6PD deficiency.

Example 4: X-linked dominant inheritance (Alport-style)

X-linked dominant inheritance is less common than X-linked recessive but has distinctive features. Affected fathers transmit the condition to all their daughters but none of their sons; affected mothers transmit to 50% of each.

          I-1                I-2
           ■─────────────────○  (affected father × unaff. mother)
                    │
   ┌────────┬───────┴───────┬──────────┐
  II-1    II-2             II-3       II-4
   □       ●                □          ●
  (unaff.) (affected,     (unaff.,   (affected,
   son —    daughter)      son)       daughter)
   no     (milder in                 (variable
   trans-  females due                severity)
   mission) to X-inactiv.)

Decision rationale.

1. Affected father, offspring distribution. I-1 is an affected male. All his daughters (II-2, II-4) are affected; none of his sons (II-1, II-3) are affected. That specific pattern — 100% of daughters, 0% of sons — is nearly pathognomonic of X-linked dominant.
2. Severity in females. Affected females are often less severely affected than affected males, a consequence of X-inactivation (lyonization) producing mosaic expression. This is characteristic of X-linked dominant.
3. Male lethality check. Some X-linked dominant conditions are male-lethal (Rett syndrome, incontinentia pigmenti) — affected males are rare or absent, and female-to-female-only transmission is seen. If the pedigree shows only affected females, consider this variant.
4. Conclusion. X-linked dominant. Examples include Alport syndrome (in its X-linked form, which accounts for roughly 80% of cases and is caused by COL4A5 variants), vitamin-D-resistant rickets (X-linked hypophosphataemia), and Rett syndrome (male-lethal).

Example 5: Mitochondrial inheritance

Mitochondrial DNA is inherited exclusively from the mother. A mitochondrial pedigree shows a strict maternal transmission pattern, with affected mothers passing the condition to all offspring and affected fathers passing it to none.

          I-1                I-2
           □─────────────────●  (affected mother)
                    │
    ┌────────┬──────┴──────┬─────────┐
   II-1    II-2          II-3      II-4
    ■       ●             ■         ●
  (all offspring of affected mother — both sons and
   daughters potentially affected, but expression varies
   due to heteroplasmy)

  II-1 partner (unaffected female):
   II-1───────○
            │
       ┌────┴────┐
     III-1     III-2
      □          ○    (NO transmission from affected father)
     unaff.   unaff.

  II-2 partner (unaffected male):
   ○───────II-2
            │
       ┌────┴────┐
     III-3     III-4
      ●          ■    (BOTH affected — from affected mother)

Decision rationale.

1. Transmission through mothers only. Offspring of affected females (II-2's children III-3, III-4) show transmission. Offspring of affected males (II-1's children III-1, III-2) do not.
2. Sex distribution. Both males and females affected, because mitochondria pass to all offspring irrespective of sex.
3. Variable expression. Heteroplasmy means the proportion of mutant mitochondrial genomes differs between cells and tissues. Affected individuals from the same mother can show very different severities, and tissues with high energy demand (muscle, brain) tend to express disease earlier.
4. Conclusion. Mitochondrial. Examples include Leber hereditary optic neuropathy (LHON), MELAS syndrome, mitochondrial encephalomyopathy, and mitochondrial DNA deletion syndromes.

How to tell them apart: a decision tree

Faced with an unfamiliar pedigree, a useful sequence of questions is:

START
  │
  ├─ Is every affected individual descended from an affected mother,
  │  and does no affected father transmit to any child?
  │    YES → MITOCHONDRIAL
  │    NO  → continue
  │
  ├─ Is transmission vertical (affected in every generation)?
  │    YES → DOMINANT (continue to distinguish AD vs XLD)
  │    NO  → RECESSIVE (continue to distinguish AR vs XLR)
  │
  ├─ [DOMINANT branch] Is there male-to-male transmission?
  │    YES → AUTOSOMAL DOMINANT
  │    NO, but affected father → all daughters affected, no sons affected
  │         → X-LINKED DOMINANT
  │    NO, ambiguous → both possible
  │
  └─ [RECESSIVE branch] Are affected individuals mostly or only male?
       YES, plus unaffected carrier mothers with affected sons → X-LINKED RECESSIVE
       NO, both sexes affected in a single sibship, often consanguineous parents
            → AUTOSOMAL RECESSIVE

Caveats: what can mislead pattern recognition

Real pedigrees often resist clean categorisation. Common confounders include:

• Reduced penetrance. Not everyone carrying a dominant variant expresses the phenotype. A pedigree with skipped generations does not rule out autosomal dominant — it suggests incomplete penetrance.
• Variable expressivity. A condition can be mild in one relative and severe in another. Mild affected relatives may be mis-recorded as unaffected, distorting the pattern.
• De novo mutations. An affected individual with two unaffected parents may carry a new variant rather than indicating recessive inheritance.
• Small families. Many modern families are too small to show pattern reliably. Two affected out of three siblings is compatible with multiple patterns.
• Ascertainment bias. The family came to attention because of the proband — so sampling is not random. Families with more affected individuals are more likely to seek counselling.
• Mosaicism. Germline mosaicism in a parent can produce multiple affected children without the parent carrying the variant in blood.

How Evagene supports this

Evagene's batch pattern-identifier screens a pedigree against autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant, and mitochondrial patterns simultaneously. For each pattern, the tool reports the features that support it (for example, "male-to-male transmission" for autosomal dominant) and the features that argue against it (for example, "affected father with all affected daughters and no affected sons" for anything other than X-linked dominant). Where multiple patterns remain compatible, Evagene ranks them and explains the ambiguity — useful for teaching, and useful for informing which molecular tests to order.

Beyond pattern identification, Evagene's Mendelian inheritance calculator computes transmission probabilities for specific offspring given a confirmed pattern, and the BayesMendel integration (BRCAPRO, MMRpro, PancPRO) applies age-dependent penetrance models for the specific cancer predispositions those models cover. For conditions outside the BayesMendel remit, the Mendelian module handles autosomal dominant, autosomal recessive, and X-linked recessive transmission with user-supplied penetrance values.

Evagene's AI interpretation can also narrate the pattern analysis in plain clinical language — a drafting aid for the report's inheritance-pattern section, not a replacement for clinical judgement.

Frequently asked questions

Related reading

• Complete pedigree symbols reference
• How to make a pedigree chart in 5 steps
• Mendelian inheritance calculator
• Hereditary cancer risk assessment
• Clinical genetics pedigree tools
• Pedigree charts for biology class