Gavin Kelsey

Research Summary

As well as genetic information, the egg and sperm also contribute epigenetic annotations that may influence gene activity after fertilisation. These annotations may be direct modifications of the DNA bases or of the proteins around which the DNA is wrapped into chromatin. Our goal is to understand whether, through epigenetics, factors such as a mother’s age or diet have consequences on the health of a child.
We examine how epigenetic states are set up in oocytes – or egg cells – and influence gene expression in the embryo. For example, repressive chromatin marks in oocytes lead to long-term silencing of genes inherited from the mother, particularly in cells that will form the placenta. We are also interested in how variations in DNA methylation come about in oocytes and whether we can use this variation as a marker for oocyte quality and embryo potential. To investigate these questions, we develop methods to profile epigenetic information in very small numbers of cells or even in single cells.

Latest Publications

The genetic landscape of Arab Population, Chechens and Circassians subpopulations from Jordan through HV1 and HV2 regions of mtDNA.
Al-Eitan L, Saadeh H, Alnaamneh A, Darabseh S, Al-Sarhan N, Alzihlif M, Hakooz N, Ivanova E, Kelsey G, Dajani R

Mitochondrial DNA (mtDNA) is widely used in several fields including medical genetics, forensic science, genetic genealogy, and evolutionary anthropology. In this study, mtDNA haplotype diversity was determined for 293 unrelated subjects from Jordanian population (Circassians, Chechens, and the original inhabitants of Jordan). A total of 102 haplotypes were identified and analyzed among the populations to describe the maternal lineage landscape. Our results revealed that the distribution of mtDNA haplotype frequencies among the three populations showed disparity and significant differences when compared to each other. We also constructed mitochondrial haplotype classification trees for the three populations to determine the phylogenetic relationship of mtDNA haplotype variants, and we observed clear differences in the distribution of maternal genetic ancestries, especially between Arab and the minority ethnic populations. To our knowledge, this study is the first, to date, to characterize mitochondrial haplotypes and haplotype distributions in a population-based sample from the Jordanian population. It provides a powerful reference for future studies investigating the contribution of mtDNA variation to human health and disease and studying population history and evolution by comparing the mtDNA haplotypes to other populations.

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Gene, 729, 1, 01 Mar 2020

DOI: 10.1016/j.gene.2019.144314

PMID: 31884104

Genome-wide assessment of DNA methylation in mouse oocytes reveals effects associated with in vitro growth, superovulation, and sexual maturity.
Saenz-de-Juano MD, Ivanova E, Billooye K, Herta AC, Smitz J, Kelsey G, Anckaert E

In vitro follicle culture (IFC), as applied in the mouse system, allows the growth and maturation of a large number of immature preantral follicles to become mature and competent oocytes. In the human oncofertility clinic, there is increasing interest in developing this technique as an alternative to ovarian cortical tissue transplantation and to preserve the fertility of prepubertal cancer patients. However, the effect of IFC and hormonal stimulation on DNA methylation in the oocyte is not fully known, and there is legitimate concern over epigenetic abnormalities that could be induced by procedures applied during assisted reproductive technology (ART).

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Clinical epigenetics, 11, 1, 19 Dec 2019

DOI: 10.1186/s13148-019-0794-y

PMID: 31856890

A KHDC3L mutation resulting in recurrent hydatidiform mole causes genome-wide DNA methylation loss in oocytes and persistent imprinting defects post-fertilisation.
Demond H, Anvar Z, Jahromi BN, Sparago A, Verma A, Davari M, Calzari L, Russo S, Jahromi MA, Monk D, Andrews S, Riccio A, Kelsey G

Maternal effect mutations in the components of the subcortical maternal complex (SCMC) of the human oocyte can cause early embryonic failure, gestational abnormalities and recurrent pregnancy loss. Enigmatically, they are also associated with DNA methylation abnormalities at imprinted genes in conceptuses: in the devastating gestational abnormality biparental complete hydatidiform mole (BiCHM) or in multi-locus imprinting disease (MLID). However, the developmental timing, genomic extent and mechanistic basis of these imprinting defects are unknown. The rarity of these disorders and the possibility that methylation defects originate in oocytes have made these questions very challenging to address.

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Genome medicine, 11, 1, 17 12 2019

DOI: 10.1186/s13073-019-0694-y

PMID: 31847873