Prader Willi Syndrome and Angelman Syndrome

Slide 1 · Prader–Willi Syndrome and Angelman Syndrome

Genomic imprinting, parent-of-origin effects, clinical phenotypes and molecular diagnosis

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain how genomic imprinting creates parent-specific allelic expression.

Compare the clinical signatures of Prader–Willi and Angelman syndromes.

Trace deletion, uniparental disomy and imprinting defects to lost gene function.

Interpret the complementary roles of methylation, deletion and SNP-based assays.

One chromosomal region produces two distinct disorders because parental origin changes gene activity.

Slide 3 · A shared locus does not imply a shared phenotype

Prader–Willi syndrome

Angelman syndrome

Loss of paternal-expression functions in 15q11.2–q13.

Characteristic hypotonia, hyperphagia and obesity.

Hypogonadism, short stature and intellectual disability.

Loss of maternal UBE3A function in relevant neurons.

Microcephaly, ataxic gait and seizures.

Intellectual disability and inappropriate laughter.

The identity of the affected parent determines which genes lack active alleles.

Slide 4 · Why genomic imprinting changes inheritance

Two alleles

An autosomal locus has maternal and paternal copies.

Parent-specific silencing

An epigenetic imprint reduces expression of one parental allele.

One functional contribution

Deletion or silencing of the expressed copy may leave no functional allele.

The functional genotype depends on allele activity, not just copy number.

Slide 5 · Imprinting is an epigenetic mechanism

The DNA sequence need not be changed to silence an allele.

Maternal and paternal versions of an autosomal locus can be functionally unequal.

Selective transcriptional repression establishes the parent-of-origin effect.

Imprinting is a property of gene expression, not simply chromosome inheritance.

Slide 6 · Maternal imprinting: The maternal allele is silent

Maternal allele SILENCED

The term specifies which parental allele is inactivated.

For maternally imprinted loci, paternal expression remains available.

The PWS-associated gene region is maternally imprinted.

Maternal imprint ≠ maternal expression.

Slide 7 · Paternal imprinting: The paternal allele is silent

Paternal allele SILENCED

A paternally imprinted gene is expressed predominantly from its maternal copy.

In relevant neurons, UBE3A shows this expression pattern.

Loss of the maternal contribution can therefore be pathogenic.

Paternal imprint ≠ paternal expression.

Slide 8 · Imprints are established before fertilization

Gametogenesis

Imprinting patterns are established during sperm or ovum formation.

Fertilization

Maternal and paternal chromosomes carry different epigenetic marks.

Embryonic development

The parent-specific patterns influence expression after fertilization.

These inherited epigenetic differences can persist in somatic cells.

Slide 9 · Imprinting is maintained through cell division

Imprinted zygote

Parent-specific marks are present at fertilization.

Mitosis

Imprint patterns are propagated to daughter cells.

Somatic tissues

Transcription can remain parent-dependent during development.

Parent-of-origin expression is a stable developmental property.

Slide 10 · CpG methylation provides an imprint mark

DNA methylation at CpG sites

Imprinting to differential CpG methylation.

Distinct methylation states can be detected with molecular assays.

A methylation difference can reveal parent-specific regulation without a DNA deletion.

An epigenetic test can identify a functional abnormality that a copy-number test misses.

Slide 11 · Imprinting-control regions coordinate nearby genes

Imprinted genes

Affected genes may be clustered rather than isolated.

Cis-acting control

Common regulatory elements govern expression across the cluster.

Regional consequence

A defect can alter several parentally expressed genes.

Regional control helps explain why PWS is not necessarily attributable to one protein-coding gene.

Slide 12 · Chromosome 15q11.2–q13: Two regulatory programs

15q11.2–q13

The source describes the PWS-associated gene set and UBE3A within this interval.

Their parent-specific expression directions differ.

The illustrated locus is schematic—not a physical gene-order or scale map.

The same deletion interval can remove different functional contributions.

Slide 13 · Normal parent-specific expression in neurons

Origin of chromosome 15

PWS-associated gene region

UBE3A in neurons

Paternal chromosome 15

ACTIVE

SILENCED

Maternal chromosome 15

SILENCED

ACTIVE

Paternal activity supplies the PWS gene region; Maternal activity supplies neuronal UBE3A.

Original schematic; PWS region and UBE3A are conceptual functional units, not physical gene-scale features.

Slide 14 · Normal PWS-region expression favors the paternal copy

PWS-associated genes are maternally imprinted.

The maternal allele is ordinarily silent for this gene set.

The paternal chromosome supplies the functional expression.

Loss of that paternal contribution produces the PWS molecular state.

PWS: Loss of paternally expressed functions.

Slide 15 · Normal neuronal UBE3A expression favors the maternal copy

UBE3A is paternally imprinted in specific brain regions.

The maternal allele is the main active copy in those neurons.

A deleted maternal copy cannot be fully replaced by the silent paternal allele.

Angelman syndrome: Loss of functional neuronal UBE3A.

Slide 16 · UBE3A imprinting is tissue-dependent

Relevant brain regions

Most other tissues

Paternal UBE3A is imprinted.

Maternal UBE3A provides essential expression.

Loss impairs neuronal synapse formation and plasticity.

Expression from both UBE3A alleles.

The paternal allele is not uniformly silenced across the body.

A single whole-body expression rule is misleading.

The relevant phenotype reflects tissue-specific imprinting, not universal gene silence.

Slide 17 · The normal expression matrix

Functional locus

Paternal chromosome

Maternal chromosome

PWS-associated genes

Expressed / active

Imprinted / silent

UBE3A in relevant neurons

Imprinted / silent

Expressed / active

UBE3A in most other tissues

Expressed

Expressed

Identify which parental copy normally supplies the functional product.

Slide 18 · Loss of a paternal versus maternal contribution

Paternal 15q loss

Maternal 15q loss

Eliminates normally active PWS-region functions.

Maternal PWS gene region remains imprinted.

Result: Prader–Willi syndrome.

Eliminates the normally active neuronal UBE3A copy.

Paternal neuronal UBE3A remains imprinted.

Result: Angelman syndrome.

Parent of origin—not merely cytoband—is decisive.

Slide 19 · Prader–Willi syndrome: Clinical signature

Intellectual disability and hypotonia.

Short stature and small hands and feet.

Profound hyperphagia with obesity.

Hypogonadism.

The source describes a combined neurodevelopmental, growth and endocrine phenotype.

Slide 20 · Hypotonia in Prader–Willi syndrome

Hypotonia

A major clinical component of the syndrome.

Occurs alongside neurodevelopmental impairment.

The feature is not by itself sufficient to assign a molecular diagnosis.

A distinctive constellation is more informative than one isolated clinical finding.

Slide 21 · Hyperphagia and obesity in Prader–Willi syndrome

Profound hyperphagia

Excessive food-seeking and intake are prominent phenotype.

Obesity is a characteristic associated manifestation.

These findings help distinguish PWS from the Angelman phenotype.

The appetite phenotype is a clinically prominent discriminator.

Slide 22 · Growth and distal extremity findings in PWS

Short stature Small hands and feet

Both features are included’ core PWS description.

They complement the metabolic and developmental findings.

No single external morphologic measurement is required to understand the imprinting mechanism.

The diagnosis is not reducible to a single dysmorphic feature.

Slide 23 · Hypogonadism adds an endocrine dimension to PWS

Hypogonadism

One of the characteristic PWS manifestations.

Occurs within a multisystem imprinting disorder.

The genetic defect affects a region rather than an isolated endocrine organ.

Clinical effects extend beyond cognition and behavior.

Slide 24 · Paternal deletion: The PWS-expression region is lost

Origin of chromosome 15

PWS-associated gene region

UBE3A in neurons

Paternal chromosome 15

DELETED

SILENCED

Maternal chromosome 15

SILENCED

ACTIVE

An intact but maternally imprinted PWS region cannot replace the lost paternal function.

Original schematic; Inactive and deleted are different molecular states.

Slide 25 · Prader–Willi syndrome from paternal deletion

Paternal deletion

A 15q11.2–q13 interval is lost from the paternal chromosome.

Maternal imprint

The corresponding maternal PWS-associated genes are normally silent.

Loss of expression

No normally active paternal gene contribution remains.

A structural chromosomal lesion produces a parent-specific functional deficiency.

Slide 26 · Why an intact maternal allele does not rescue PWS

The DNA of the maternal PWS region may be present.

Presence of an allele does not guarantee transcriptional activity.

The maternally imprinted state makes that allele functionally unavailable.

Thus, the effect resembles loss of the active copy.

Molecular copy number and functional gene dosage are different concepts.

Slide 27 · Maternal uniparental disomy causes PWS

Origin of chromosome 15

PWS-associated gene region

UBE3A in neurons

Paternal chromosome 15

— no paternal copy —

— no paternal copy —

Maternal chromosome 15

SILENCED (both maternal copies)

ACTIVE (both maternal copies)

Two maternal chromosome 15 copies leave no paternal-expression PWS gene set.

For this UPD schematic, the maternal-row functional state applies to both inherited chromosome copies.

Slide 28 · Uniparental disomy changes chromosome origin

Uniparental disomy (UPD) means both copies of a chromosome pair come from one parent.

Maternal UPD of chromosome 15 can result in PWS.

Cytogenetic copy number may remain diploid despite complete loss of paternal origin.

UPD is an inheritance-origin abnormality, not necessarily a deletion.

Slide 29 · PWS from an imprinting defect

Paternal chromosome present

The chromosome need not be deleted.

Incorrect epigenetic identity

The paternal PWS region carries a maternal imprint.

Paternal region silenced

Expression is absent as if paternal activity were missing.

Imprint errors can phenocopy deletion or maternal UPD.

Slide 30 · PWS is a multigene-expression disorder

Robbins does not attribute the entire syndrome to a single gene.

A series of paternally expressed genes in 15q11.2–q13 is implicated.

Several implicated transcripts include small nucleolar RNAs.

The exact contribution of each component is not fully defined in the source.

Avoid inventing a single-gene mechanism for this regional imprinting disorder.

Slide 31 · Small nucleolar RNAs are noncoding effectors

Small nucleolar RNAs (snoRNAs)

They are noncoding RNAs, not translated into protein.

The source associates them with post-transcriptional modification of ribosomal RNA and other small nuclear RNAs.

Loss of these functions is believed to contribute to the PWS phenotype.

RNA function—not merely protein loss—belongs in the disease model.

Slide 32 · The exact snoRNA pathogenesis remains uncertain

The source assigns a contributing role to small nucleolar RNA dysfunction.

It explicitly states that precise pathogenic mechanisms remain unclear.

Any detailed, linear pathway from one snoRNA to obesity or hypogonadism would exceed this source.

Distinguish established parent-of-origin causality from unresolved downstream biology.

Slide 33 · Three distinct lesions converge on PWS

Paternal deletion

Normally expressed paternal genes are removed.

Maternal UPD

Only maternally imprinted copies are inherited.

Paternal imprinting defect

Present paternal genes receive the wrong silent state.

All three eliminate the expected paternal PWS-region expression.

Slide 34 · Angelman syndrome: Clinical signature

Intellectual disability and microcephaly.

Ataxic gait and seizures.

Inappropriate laughter.

A neuronal UBE3A-expression defect underlies the phenotype.

Angelman has a dominant neurologic phenotype rather than the classic PWS appetite phenotype.

Slide 35 · Ataxic gait is a major Angelman clue

Ataxic gait

Gait ataxia among the characteristic manifestations.

It accompanies intellectual disability and seizures.

The sign is part of a broader neuronal disorder, not an isolated motor condition.

A motor-coordination abnormality is clinically discriminating.

Slide 36 · Seizures contribute to Angelman phenotype

Seizures

A cardinal manifestation in the source description.

Occurs with microcephaly and impaired neurodevelopment.

The condition is linked to loss of UBE3A-related neuronal function.

Clinical neurology and genomic imprinting intersect directly.

Slide 37 · Microcephaly signals neurodevelopmental involvement

Microcephaly

Robbins explicitly identifies microcephaly in Angelman syndrome.

It occurs alongside the characteristic ataxic and seizure phenotype.

The source does not require a particular head-circumference cutoff here.

Use the source-defined clinical pattern without inventing diagnostic thresholds.

Slide 38 · Inappropriate laughter: Recognizable but not diagnostic

Inappropriate laughter

A distinctive behavioral manifestation noted.

Should be interpreted together with developmental and neurologic findings.

The molecular diagnosis depends on parental gene expression, not this symptom alone.

Behavioral phenotype complements but cannot replace molecular characterization.

Slide 39 · Maternal deletion removes active neuronal UBE3A

Origin of chromosome 15

PWS-associated gene region

UBE3A in neurons

Paternal chromosome 15

ACTIVE

SILENCED

Maternal chromosome 15

DELETED

DELETED

Paternally silenced neuronal UBE3A cannot replace the missing maternal UBE3A.

Original schematic; Deletion may also remove neighboring loci, while the illustrated Angelman mechanism centers on UBE3A.

Slide 40 · Angelman syndrome from maternal deletion

Maternal deletion

A 15q11.2–q13 interval containing UBE3A is lost.

Paternal imprint

The paternal UBE3A copy is silenced in relevant neurons.

Functional absence

Those neurons lack maternal UBE3A activity.

A deletion of the opposite parental origin has a different outcome.

Slide 41 · Paternal UBE3A cannot fully compensate in neurons

The paternal gene is present in many Angelman mechanisms.

Its imprinting silences expression in specific brain regions.

Therefore, a maternal deletion can remove the only normally active neuronal allele.

The functional deficit is tissue dependent.

Slide 42 · Paternal uniparental disomy can cause Angelman

Origin of chromosome 15

PWS-associated gene region

UBE3A in neurons

Paternal chromosome 15

ACTIVE (both paternal copies)

SILENCED (both paternal copies)

Maternal chromosome 15

— no maternal copy —

— no maternal copy —

Two paternal copies do not provide a maternally active neuronal UBE3A allele.

For this UPD schematic, the paternal-row state applies to both inherited chromosome copies.

Slide 43 · Angelman from a maternal imprinting defect

Maternal chromosome present

UBE3A DNA need not be physically deleted.

Incorrect imprint

Maternal UBE3A acquires a paternal-type epigenetic state.

Both copies silent in neurons

The functionally active maternal contribution is lost.

An epigenetic state error can mimic a maternal deletion.

Slide 44 · Three lesion classes converge on Angelman

Maternal deletion

Active maternal neuronal UBE3A is removed.

Paternal UPD

No maternally derived UBE3A allele is inherited.

Maternal imprinting defect

The maternal UBE3A allele is inappropriately silenced.

Each mechanism disrupts functional maternal UBE3A expression in neurons.

Slide 45 · UBE3A encodes a ubiquitin ligase

UBE3A Ubiquitin ligase

UBE3A codes for an enzyme participating in target-protein ubiquitination.

It catalyzes the transfer of activated ubiquitin to protein substrates.

The source links UBE3A deficiency to synapse formation and plasticity.

Angelman is linked to a defined protein-coding gene and neuronal function.

Slide 46 · Ubiquitin transfer: A conceptual UBE3A function

Activated ubiquitin

Ubiquitin is available for enzymatic transfer.

UBE3A activity

The ligase catalyzes transfer toward target substrates.

Substrate ubiquitination

The target protein receives ubiquitin.

This is an enzymatic role, not a full substrate-specific signaling pathway.

Slide 47 · UBE3A loss affects neuronal connectivity

Loss of maternal UBE3A

Functional UBE3A is absent in relevant neurons.

Synaptic disturbance

The source describes inhibition of synapse formation and synaptic plasticity.

Neurologic syndrome

Marked neurodevelopmental, motor and seizure manifestations emerge.

Do not infer unprovided substrates or quantitative effects from this model.

Slide 48 · UBE3A expression is not identical in every tissue

Context

Paternal UBE3A

Maternal UBE3A

Specific brain regions

Imprinted / inactive

Active

Most other tissues

Expressed

Expressed

Maternal deletion, relevant neurons

Imprinted / inactive

Absent

Tissue-specific imprinting explains the predominance of neurologic consequences.

Slide 49 · Clinical comparison at the bedside

Phenotype

Prader–Willi

Angelman

Neurodevelopment

Intellectual disability

Intellectual disability

Motor / tone

Hypotonia

Ataxic gait

Growth / head

Short stature; small hands and feet

Microcephaly

Behavior / feeding

Hyperphagia; obesity

Inappropriate laughter

Additional hallmark

Hypogonadism

Seizures

The phenotypes overlap in cognition but differ in their defining associated features.

Slide 50 · Molecular comparison: What is missing?

Question

Prader–Willi

Angelman

Locus

15q11.2–q13

15q11.2–q13

Required active origin

Paternal

Maternal (neuronal UBE3A)

Pathogenic deletion origin

Paternal

Maternal

Pathogenic UPD origin

Two maternal copies

Two paternal copies

Imprinting defect

Paternal gets maternal-type imprint

Maternal gets paternal-type imprint

Always state the parent of origin when describing a 15q lesion.

Slide 51 · Deletion of the same interval: Reciprocal outcomes

Paternal deletion

Maternal deletion

Removes paternal PWS-associated expression.

Maternal PWS region is silent.

Leads to the PWS phenotype.

Removes maternal neuronal UBE3A expression.

Paternal neuronal UBE3A is silent.

Leads to the Angelman phenotype.

Deletion location alone does not determine the syndrome.

Slide 52 · Uniparental disomy: Opposite parental directions

Two maternal copies

Two paternal copies

Diploid chromosome number may appear normal.

Missing paternal-origin PWS functions.

Molecular consequence: PWS.

Diploid chromosome number may appear normal.

Missing maternal-origin neuronal UBE3A.

Molecular consequence: Angelman.

UPD requires determining chromosome origin, not only chromosome count.

Slide 53 · Imprinting defects: The wrong epigenetic label

Prader–Willi

Angelman

Paternal chromosome acquires a maternal-type imprint.

PWS-region expression is suppressed.

No deletion is required.

Maternal chromosome acquires a paternal-type imprint.

Neuronal UBE3A expression is suppressed.

No deletion is required.

The physical allele can be intact yet functionally unavailable.

Slide 54 · Structural normality does not exclude imprinting disease

Two chromosomes ≠ two active copies

Deletion is a DNA copy-number abnormality.

UPD is a parent-of-origin abnormality that can preserve copy number.

An imprint defect alters epigenetic expression without necessarily deleting DNA.

Three mutation classes can converge on the same expression phenotype.

Slide 55 · Robbins’ approximate mechanism frequencies require context

For PWS, the text specifically reports paternal deletions in about 65–70% of cases.

The figure gives illustrative categories: Deletion ~70%; UPD ~20–25%; Imprinting defect ~1–4%.

Do not interpret these summary figures as identical subtype frequencies for both syndromes.

Percentages here reproduce the textbook presentation and are not updated syndrome-specific estimates.

Slide 56 · What different assay classes actually measure

Assay class

Primary biological signal

Key question

Methylation assay

CpG methylation state

Is the expected parent-specific imprint present?

FISH deletion assessment

Presence of chromosomal DNA interval

Is a segment physically deleted?

SNP-array analysis

Genotype and copy-number pattern

Is there copy loss or informative loss of heterozygosity?

One assay signal should not be treated as equivalent to another.

Slide 57 · Methylation analysis is central to both disorders

Methylation status of marker genes as a molecular diagnostic basis.

Parent-specific methylation can reveal an abnormal imprinting pattern.

It complements structural deletion assays.

A methylation result describes epigenetic state; It may not itself assign the causal mutation class.

Imprinting disorders require more than a conventional chromosome count.

Slide 58 · Bisulfite treatment exposes CpG methylation

Unmethylated C

Sodium bisulfite converts cytosine to uracil.

Methylated C

Methylated cytosine is protected and remains cytosine.

Sequence comparison

Downstream readout distinguishes the original methylation states.

Bisulfite-based methods translate an epigenetic difference into a sequence-readable difference.

Slide 59 · Other methylation-detection principles

Proteins that selectively bind methylated DNA can enrich methylated fragments.

Methylation-sensitive restriction enzymes discriminate DNA by cleavage behavior.

Direct-read technologies can detect modified bases using polymerase or nanopore signals.

Multiple assay technologies target the same molecular property: DNA methylation.

Slide 60 · FISH reveals deletion, not the entire imprinting mechanism

FISH

Fluorescence in situ hybridization can detect chromosome 15 interval deletions.

It does not directly measure parent-specific DNA methylation.

A patient with UPD or a pure imprinting defect may lack the deletion sought by FISH.

A negative deletion assay cannot exclude an imprinting disorder.

Slide 61 · SNP arrays can expose copy-neutral inheritance clues

SNP arrays combine copy-number information with genotype calls.

Decreased heterozygosity in regions affected by certain UPD states.

Diploid copy number and unusual genotype patterns can coexist.

Parental-origin interpretation requires suitable informative evidence.

Copy-neutral genetic alterations can be invisible to tests limited to dosage.

Slide 62 · An illustrative copy-neutral UPD pattern

Two chromosome copies

A diploid dosage signal is present.

Unexpected genotype pattern

Regions may show reduced heterozygosity in SNP calls.

Interpret origin

A UPD mechanism can explain loss of expected parental contribution.

This is a conceptual interpretation—not a fabricated patient SNP plot.

Slide 63 · Combining assays: Complementary inferences

Observation

What it supports

What remains unresolved

Deletion detected

Structural loss in 15q region

Parental origin / functional pattern

Abnormal methylation

An imprinting-pattern abnormality

Deletion versus UPD versus imprint defect

Diploid copy number

No detected deletion at assay resolution

UPD / imprint abnormality may remain

SNP loss of heterozygosity

Possible copy-neutral inheritance abnormality

Parent of origin / full molecular classification

These are interpretation principles, not a laboratory testing guideline.

Slide 64 · Diagnostic reasoning: Normal chromosome count

A child has a characteristic imprinting-disorder phenotype. Routine chromosome counting identifies two copies of chromosome 15.

Clinical / laboratory clues

Chromosome copy number is not equivalent to parental origin.

Imprinting defects do not necessarily alter DNA dosage.

Is a chromosome-15 imprinting disorder excluded?

Slide 65 · Interpretation: Normal dosage may conceal UPD

No

Two copies can both be maternally or paternally inherited.

An imprint defect can silence an otherwise present allele.

Parent-specific methylation and additional molecular tests address the functional question.

A normal chromosome count does not exclude PWS or Angelman syndrome.

Slide 66 · Case application: Prader–Willi phenotype

A child with developmental impairment has hypotonia, short stature, striking hyperphagia, obesity and hypogonadism.

Clinical / laboratory clues

Clinical pattern strongly resembles the PWS phenotype.

A paternal deletion, maternal UPD or paternal imprint error can converge on this pattern.

Which parental-expression program is missing?

Slide 67 · PWS case: Name the lost functional origin

Paternal PWS-region expression

The maternal PWS-associated region is normally imprinted.

Deleting the paternal interval removes its functional contribution.

Maternal UPD and paternal imprint defects also remove effective paternal expression.

The correct molecular abstraction is absence of paternally expressed PWS-region genes.

Slide 68 · Case application: Angelman phenotype

A child has intellectual disability, microcephaly, ataxic gait, seizures and recurrent inappropriate laughter.

Clinical / laboratory clues

The combined features fit the Angelman phenotype.

Neuronal UBE3A is normally expressed from the maternal allele.

Which gene and parental origin explain the pattern?

Slide 69 · Angelman case: Identify the affected functional gene

Maternal UBE3A in neurons

Loss of maternal UBE3A removes the active neuronal allele.

The paternally inherited neuronal UBE3A allele is imprinted.

The lost ligase activity is linked to altered synapse formation and plasticity.

The affected parental copy is the maternal UBE3A allele.

Slide 70 · Mechanism check: Predict the syndrome

Genomic finding

Expected syndrome

Mechanistic reason

Paternal 15q11.2–q13 deletion

Prader–Willi

Loss of active PWS-region genes

Maternal 15q11.2–q13 deletion

Angelman

Loss of active neuronal UBE3A

Two maternal chromosome 15 copies

Prader–Willi

No paternal-origin PWS activity

Two paternal chromosome 15 copies

Angelman

No maternal-origin neuronal UBE3A

The parent-of-origin rule correctly predicts these four textbook mechanisms.

Slide 71 · Final synthesis: The causal rule

Imprinted alleles are present but normally silent in relevant cells.

PWS is linked to missing paternal-expression functions in 15q11.2–q13.

Angelman is linked to missing maternal UBE3A function in neurons.

Deletion, UPD and imprinting errors can produce the same functional deficit.

Methylation, copy-number and SNP information answer complementary questions.

Always ask: Which parental allele is normally active, and what made it unavailable?

Slide 72 · Primary source and scope

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026).

Chapter 5, sections on Genomic Imprinting and Prader–Willi Syndrome and Angelman Syndrome.

Molecular diagnostic explanations also draw on adjacent sections on SNP arrays and epigenetic alterations.

All diagrams are original editable conceptual schematics; textbook figure 5.31 was not reproduced.