Genomic imprinting disorders in humans: a mini-review

Abstract

Mammals inherit two complete sets of chromosomes, one from the father and one from the mother, and most autosomal genes are expressed from both maternal and paternal alleles. Imprinted genes show expression from only one member of the gene pair (allele) and their expression are determined by the parent during production of the gametes. Imprinted genes represent only a small subset of mammalian genes that are present but not imprinted in other vertebrates. Genomic imprints are erased in both germlines and reset accordingly; thus, reversible depending on the parent of origin and leads to differential expression in the course of development. Genomic imprinting has been studied in humans since the early 1980's and accounts for several human disorders. The first report in humans occurred in Prader-Willi syndrome due to a paternal deletion of chromosome 15 or uniparental disomy 15 (both chromosome 15s from only one parent) and similar genetic disturbances were reported later in Angelman syndrome.

Gene expression pattern ofIGF2,PHLDA2,PEG10andCDKN1Cimprinted genes in spontaneous miscarriages or fetal deaths

“…12,45 The expression of imprinted genes may be tissue and limits nutrient provision acting to preserve such resources. 35,44 Misregulation of imprinted genes expression caused by deletion and inappropriate silencing or loss of imprinting has been implicated in marker of fetal growth.…”

“…Thus, a potential role of genomic imprinting in the tissues differentiation is to determine the transcription rate of genes that influence growth through a fine balance between the expression of two parental alleles. 12 The majority of current research has been focused on the study of expression/methylation of human imprinted genes using term placentas associated with IUGR. 3,25,26,28 The most recent work in this field evaluates the methylation values of six imprinted genes in human miscarriages and stillbirths.…”

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

“…40 Causes of imprinting disorders range from chromosomal and genetic abnormalities to epigenetic abnormalities and one imprinting disorder can result from a variety of molecular mechanisms. Chromosomal and genetic causes include uniparental disomies, chromosomal deletion, duplication, translocation, inversion and point mutation, all of which change the dosage of normal imprinted gene product(s).…”

“…A de novo interstitial deletion affecting the entire imprinted domain, and a maternal uniparental disomy are the major causes of PWS (B70% and B25-30%, respectively), and about 1-3% of PWS is caused by abnormal imprinting. 40,66 A small proportion of PWS patients with an imprinting defect carry a deletion at the PWS-imprinting center that lies at the promoter/exon 1 of SNRPN (Figure 2). 66 However, most imprinting defects represent primary epimutations derived from the paternal grandmother.…”

Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming

“…All imprinted genes show either maternal-specific or paternal-specific mono-allelic expression, and their proper expression is essential for normal development, fetal growth, nutrient metabolism and adult behavior. In humans, genetic and epigenetic disturbances in expression of the imprinted genes can cause well-known malformation disorders, such as Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome and Silver-Russell syndrome [5][6][7].…”