Imprinting & UPD pedigree software

Imprinting disorders defeat the usual recurrence-risk heuristics because the molecular mechanism determines the number, not the pedigree shape alone. Evagene models four distinct mechanisms and applies the parent-of-origin rule for imprinting-centre defects.

Four mechanisms, four different recurrence-risk numbers

  • Deletion — typically sporadic; low recurrence unless a parent carries a structural variant.
  • Uniparental disomy (UPD) — typically sporadic; recurrence dominated by the rare cases of parental meiotic instability.
  • Imprinting-centre defect — can carry substantial recurrence risk depending on the configuration.
  • Point mutation in the imprinted gene — follows classical Mendelian recurrence for the underlying pattern.

The parent-of-origin rule

For imprinting-centre defects, the transmitting parent's sex determines which syndromic phenotype appears in offspring. A paternally-inherited defect at 15q11-13 presents as Prader-Willi syndrome; a maternally-inherited defect at the same locus presents as Angelman syndrome. Evagene's offspring-risk output depends on both the confirmed molecular mechanism and the transmitting parent's sex.

Canonical disorders

Prader-Willi syndrome
Paternal loss of expression at 15q11-13; neonatal hypotonia, hyperphagia, intellectual disability.
Angelman syndrome
Maternal loss of UBE3A at 15q11-13; severe developmental delay, ataxia, seizures.
Beckwith-Wiedemann syndrome
Overgrowth syndrome, 11p15.5; Wilms tumour risk elevated.
Silver-Russell syndrome
Growth restriction, body asymmetry; 11p15.5 and chr7 UPD mechanisms.
Transient neonatal diabetes mellitus (TNDM)
Imprinted 6q24 region; self-resolving, may recur in adolescence.

Who this is for

Reproductive-medicine specialists, clinical geneticists, and genetic counsellors counselling couples after a previous pregnancy affected by an imprinting disorder. The couple's next-pregnancy recurrence-risk number depends on the confirmed molecular mechanism in the proband — which is exactly what Evagene's engine takes as input.

See also

Model imprinting / UPD on the pedigree

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