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Maintaining genetic and chromosomal stability in mammalian germ cells

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Current Research Interests

Characterising how genetic and chromosomal stability is maintained the mammalian germline


Ian Adams studied molecular biology as an undergraduate at the University of Edinburgh before carrying out his PhD research on chromosome segregation in yeast under the supervision of Dr. John Kilmartin at the MRC Laboratory of Molecular Biology in Cambridge. He then undertook post-doctoral research on mouse germ cell development in Dr. Anne McLaren's laboratory at the Gurdon Institute in Cambridge, before returning to Edinburgh supported by a fellowship from the Lister Institute of Preventive Medicine. Ian Adams' research at the MRC Human Genetics Unit in the MRC Institute of Genetics and Molecular Medicine is aimed at understanding how genetic and chromosomal stability is maintained in mammalian germ cells.

My research in a nutshell

Our research is trying to find out how the body makes sure that parents pass the right number of chromosomes on to their children. Mistakes in this process are very common in humans and cause miscarriage, infertility, and Down's Syndrome.

We know that most of the mistakes that cause embryos to inherit the wrong number of chromosomes happen when eggs are being made in the mother, and that these mistakes are very common in older mothers. However the behaviour of the chromosomes in developing eggs is difficult to study in humans because these cells are rare and only found in the ovary deep inside the body.

Mice are much better at passing the right number of chromosomes on to their children than humans, and we have found a new gene that helps mice do this. Female mice that have mutations in this gene make eggs carrying the wrong number of chromosomes. The mistakes happening in these mutant mouse eggs mimic some of the mistakes that happen in human eggs. We hope that by finding the genes that help mouse eggs and sperm carry the right number of chromosomes, we might be able to help humans eggs do the same.

Research Interests

The aim of this programme is to investigate the mechanisms that germ cells and pluripotent cells use to promote genetic and chromosomal stability from generation to generation. Errors in this process are likely to result in new mutations and chromosomal changes in the sperm or egg that can be transmitted to the next generation. In particular, errors in chromosome segregation in the developing germ cells will cause aneuploidies that can be transmitted to the next generation causing embryonic lethality, miscarriage, or clinical disorders such as Down's syndrome. Aneuploidy is a leading cause of miscarriage and infertility in older women and the high estimated frequencies of aneuploidy in human oocytes (~30%, but strongly age-dependent), miscarriages (~70%) and live-births (~0.6%) make understanding the pathways that can act to promote faithful chromosome segregation in oocytes of particular importance for human health.

Using mice as an experimental system we have identified a novel genetic pathway that operates specifically in germ cells and pluripotent cells to promote genetic and chromosomal stability. Mutations in Tex19.1 that is part of this pathway cause defects in chromosome segregation in meiosis in male and female germ cells. Aneuploidies arise at a high frequency in the meiotic oocytes of Tex19.1-/- mutant female mice, and model some aspects of the oocyte aneuploidy that is prevalent in older human females. Tex19.1 also appears to be part of a host defence system that protects germ cells and pluripotent cells against retrotransposons, a type of mobile genetic element derived from retroviruses. Tex19.1 appears to play a role in defending the genome from the mutagenic activity of retrotransposons, and is part of a group of germline genome defence genes that are co-ordinately regulated primarily by promoter DNA methylation. This programme will use molecular genetic and cell biological techniques in mouse embryonic stem cells, oocytes and spermatocytes to investigate how this novel genetic pathway interacts with the mitotic and meiotic chromosome segregation machineries. The work that is being carried out in this research programme will advance our understanding of processes and pathways that can influence the rates of mutation, and in particular aneuploidy, in human sperm and eggs.

Research Groups

Prof. Richard Meehan, MRC Human Genetics Unit, MRC IGMM, University of Edinburgh

Prof. Wendy Bickmore, MRC Human Genetics Unit, MRC IGMM, University of Edinburgh

Prof. Javier Caceres, MRC Human Genetics Unit, MRC IGMM, University of Edinburgh

Dr. Norah Spears, Centre for Integrative Physiology, University of Edinburgh

Prof. Niki Gray, Centre for Reproductive Health, University of Edinburgh


Reproductive Biology Honours, Core

Education/Academic qualification

Doctor of Philosophy (PhD), Spindle pole body duplication in the budding yeast Saccharomyces cerevisiae, University of Cambridge

Award Date: 1 Jan 1999

Bachelor of Science, University of Edinburgh

Award Date: 1 Jan 1995


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