Imprinted Gene Diseases-SPECTRUM FERTILITY GROUP

Imprinted gene diseases

Genomic imprinting is a normal form of gene regulation that causes a subset of mammalian genes to be expressed from one of the two parental chromosomes. Some imprinted genes are expressed from the maternally inherited chromosomes and others from the paternally inherited chromosomes. The monoallelic parent of origin-specific expression of imprinted genes in mammals is regulated by differentially DNA methylated imprinting control regions (ICRs).

Imprinted gene diseases are mostly caused by abnormal DNA methylation in imprinting control regions. the disorders of imprinted gene can cause the defect of embryo development, brain function et.al.

As French National Heath Data showed, incidence rate of imprinted gene disease was 1.4‰ for infants from normal conception and 3‰ for IVF infants. It was mostly caused by abnormal DNA methylation. However, there is no specific method to diagnose, screen or even cure the imprinted gene disease.

Imprinted diseases can be potentially detected by PIMS

If the regions are covered by the sequencing data

1
Angelman Syndrome/ Prader-Willi Syndrome
2
Beckwith-Wiedemann syndrome
3
Silver-Russell syndrome
4
Nasopalpebral lipoma-coloboma syndrome
5
Transient neonatal diabetes mellitus
6
Hepatocellular carcinoma
7
Intellectual developmental disorder
8
Bladder cancer
9
Osteosarcoma
10
Precocious puberty

Imprinted gene defects can be identified by PIMS

·The standard methylation patterns of ICRs (Imprinting Control Regions) are established according to the embryos with healthy live birth.

·A gene named GNAS is linked to the birth defect of Pseudohypoparathyroidism (Monk et al,2019).

Gao et.al., Cell Research, 2023

Epigenetic Modifications

Regulatory gene expression that can be stably maintained with cell division without changing the DNA sequence

DNA methylation
Histone modification
Non-coding RNA
Chromosome structure

DNA Methylation

Epigenetics and IVF