Imprinting Disorders

Rebecca S Henkhaus, University of Kansas Medical Center, Kansas City, Kansas, USA
Andrew P Feinberg, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Emily L Niemitz, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Merlin G Butler, University of Kansas Medical Center, Kansas City, Kansas, USA

Published online: September 2011

DOI: 10.1002/9780470015902.a0005477.pub2

Genomic imprinting is an example of epigenetic inheritance in which differences in gene function depend on whether the allele was inherited from the mother or father. Many disorders appear to involve epigenetic alterations to imprinted genes. Genes involved in imprinting play important roles in both pre- and post-natal growth and neurodevelopment. Imprinting disorders include several childhood genetic disorders such as Prader–Willi, Angelman and Beckwith–Wiedemann syndromes, as well as several types of cancer including Wilms tumour. Recent evidence suggests a correlation between assisted reproductive technologies (ART) and imprinting disorders, a phenomenon requiring more in-depth studies as the prevalence of ART is increasing. The mechanism of normal imprinting as well as its perturbation in disease is becoming understood and amenable to experimentation.

Key Concepts:

  • Imprinted genes are expressed in a parent-of-origin-dependent manner. Imprinting disorders result from genetic abnormalities in imprinted genes.
  • Approximately 1% of the human genome is imprinted, a process which occurs during gamete development.
  • Imprinted genes are generally associated with growth, neurodevelopment and epigenetics.
  • The first imprinted genes discovered were IGF2 (paternally expressed) and H19 (maternally expressed), both located at 11p15.
  • There is an imprinted gene cluster located at 15q11–q13, associated with Prader–Willi and Angelman syndromes. Imprinted genes/transcripts within this region include NDN, MAGEL2, SNURF-SNRPN, SNORD116, SNORD115 and UBE3A.
  • Well-characterised imprinting disorders include Prader–Willi syndrome (PWS), Angelman syndrome (AS), Beckwith–Wiedemann syndrome (BWS), Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP), Silver–Russell syndrome (SRS) and transient neonatal diabetes mellitus (TNDM).
  • Imprinted genes are associated with many types of cancers, primarily due to a process called loss of imprinting (LOI) which leads to aberrant gene expression. Cancers known to be associated with imprinted genes include Wilms tumour in children, and adult cancers of the ovary, lung, colon and liver.
  • The relationship between artificial reproductive technology (ART) and imprinting disorders is currently being investigated. There is evidence to support a correlation between ART and imprinting disorders which result from loss of maternally imprinted genes such as AS and BWS.

Keywords: imprinting; imprinting disorders; gene methylation; Prader–Willi syndrome; Angelman syndrome; Beckwith–Wiedemann syndrome; uniparental disomy; assisted reproductive technology

Figure 1. Types and mechanisms of uniparental disomy.
Figure 2. Chromosome 11 ideogram illustrating 11q15.5, the imprinted region critical in BWS, SRS and several types of cancer.
Figure 3. Chromosome 15 ideogram illustrating 15q11–q13, the imprinted region critical in PWS and AS.
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 Further Reading
    Buiting K (2010) Prader–Willi syndrome and Angelman syndrome. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics 154C(3): 365–376.
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    Koerner MV, Pauler FM, Huang R and Barlow DP (2009) The function of non-coding RNAs in genomic imprinting. Development 136(11): 1771–1783.
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    Weaver JR, Susiarjo M and Bartolomei MS (2009) Imprinting and epigenetic changes in the early embryo. Mammalian Genome 20(9–10): 532–543.
 Web Links
    ePath Angelman Syndrome; MIM number:105830 OMIM. http://www.ncbi.nlm.nih.gov/omim/105830
    ePath Beckwith–Wiedemann Syndrome; MIM number:130650 OMIM. http://www.ncbi.nlm.nih.gov/omim/130650
    ePath Cyclin-dependent Kinase Inhibitor 1C (p57, Kip2) (CDKN1C); Locus ID: 1028. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1028
    ePath Cyclin-dependent Kinase Inhibitor 1C (p57, Kip2) (CDKN1C); MIM number: 600856. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600856
    ePath GNAS Complex; MIM number: 139320. OMIM: http://www.ncbi.nlm.nih.gov/omim/139320
    ePath H19, Imprinted Maternally Expressed Untranslated mRNA (H19); Locus ID: 8043. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=8043
    ePath H19, Imprinted Maternally Expressed Untranslated mRNA (H19); MIM number: 103280. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?103280
    ePath Insulin-like Growth Factor 2 (Somatomedin A) (IGF2); Locus ID: 3481. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3481
    ePath Insulin-like Growth Factor 2 (somatomedin A) (IGF2); MIM Number: 147470. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?147470
    ePath KCNQ1 Overlapping Transcript 1 (KCNQ1OT1); Locus ID: 10984. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=10984
    ePath KCNQ1 Overlapping Transcript 1 (KCNQ1OT1); MIM number: 604115. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604115
    ePath KQT-like Subfamily, Member 1 (KCNQ1); Locus ID: 3784. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3784
    ePath KQT-like Subfamily, Member 1 (KCNQ1); MIM number: 192500. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?192500
    ePath Prader–Willi Syndrome; MIM number:176270. OMIM: http://www.ncbi.nlm.nih.gov/omim/176270
    ePath Pseudohypoparathyroidism; MIM number:103580 OMIM: http://www.ncbi.nlm.nih.gov/omim/103580
    ePath Silver–Russell Syndrome; MIM number:180860 OMIM: http://www.ncbi.nlm.nih.gov/omim/180860
    ePath The Medical Research Council International Centre for Mouse Genetics Imprinting Maps. http://www.mousebook.org/catalog.php?catalog=imprinting

Related Sub-Topics:

Genes, Molecules and Cellular Processes | Developmental Disorders | Epigenetics and Disease
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Article Title: Imprinting Disorders
 
How to Cite close
Henkhaus, Rebecca S, Feinberg, Andrew P, Niemitz, Emily L, and Butler, Merlin G(Sep 2011) Imprinting Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005477.pub2]