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The University of Southampton

Emeritus Professor Patricia Jacobs OBE, FRS, FRS(Edin), BSc(hons), DSc

Honorary Professor of Human Genetics, Co-director of Research, Wessex Regional Genetics Laboratory

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Professor Patricia Jacobs is Honorary Professor of Human Genetics within Medicine at the University of Southampton.


BSc (hons) in Zoology, St Andrew’s University, Fife, Scotland (1956)
DSc, St Andrew’s University, Fife, Scotland. Thesis entitled “Cytogenetic Studies” (1966)

Honours and Distinctions

D’Arcy Thomson Medal in Zoology; Honours Class Medal in Zoology (1956)
Sykes Medal for DSc thesis (1966)
Elected Fellow of the Royal Society of Edinburgh (1977)
Allan Award from the American Society of Human Genetics (1981)
University of Hawaii Regent’s Medal for Excellence in Research (1983)
Fellowship of the Royal College of Pathologists (1987)
Elected Fellow of the Royal Society (1993)
Fellowship of the Royal College of Physicians of Edinburgh (1998)
Awarded Premio Phoenix Anni-Verdi for Research in Human Genetics (1998)
Founder Fellow of the Academy of Medical Sciences (1998)
Awarded OBE (1999)
Mauro Baschirotto Award from the European Society of Human Genetics (1999)
Fellowship of the Royal College of Obstetricians and Gynaecologists (1999)
Honorary DSc – University of St. Andrews (2002)
Elected Foreign Associate of the National Academy of Sciences of the USA (2009)
Awarded March of Dimes Prize in Developmental Biology (2011)

Appointments held

Research Assistant to Dr Kathleen Stein at Mount Holyoke College, Massachussetts, USA (1956-1957)

Scientist The Medical Research Council (1957-1972)

Section Head of the Cytogenetics Section (1966)

Permanent member of the MRC’s Scientific Staff (1966)
Promoted to Special Appointment (1970)

University of Edinburgh Honorary Senior Lecturer in the Department of Medicine (1966-1972)

Year’s sabbatical leave spent with Professor Dan Lindsley in the Department of Biology, University of California at San Diego (1970-1971)

Professor in the Department of Anatomy and Reproductive Biology, University of Hawaii School of Medicine (1972-1985)

Professor and Chief of the Division of Human Genetics in the Department of Pediatrics, Cornell University Medical College, New York (1985-1987)

Director, Wessex Regional Genetics Laboratory (1988-2001)

Honorary Professor of Human Genetics, Faculty of Medicine, University of Southampton (1988-present)

Co-director of Research, Wessex Regional Genetics Laboratory (2001-present)

Research interests

My 56 years of research have been devoted to human cytogenetics. I entered the field at an exciting time in the late 1950s. I made the first observation of a human chromosome abnormality in 1959 namely the additional X chromosome in Klinefelter syndrome. My main interests have always been in the population aspects of human chromosome abnormalities. I have also published widely on the frequency and mechanisms of origin of chromosome abnormalities. One of the main aspects of this research was the cytogenetic study of spontaneous fetal loss; this occurs in about 15% of all human pregnancies that are clinically recognised and 50% of all such pregnancies have a cytogenetic abnormality recognisable at the level of the light microscope.

My recent research has focused on the mechanism of origin of structural chromosome abnormalities detected by aCGH. We examined 173 patients and their parents with physical and/or neurological abnormalities and a de novo imbalance identified by aCGH. Breakpoint intervals were screened for the presence of low copy repeats (LCRs) to distinguish between rearrangements resulting from non-allelic homologous recombination (NAHR) and those due to other mechanisms. We identified significant differences in both size and parental origin between the LCR-mediated and non-LCR groups. Non-LCR imbalances were evenly distributed among the four size intervals we defined, whereas LCR-mediated rearrangements had a narrow size distribution, between 1 and 5Mb. Among the LCR-mediated rearrangements there were equal numbers of maternally and paternally derived cases, while the non-LCR rearrangements showed a significant excess of paternal cases over a wide size range. The paternal imbalances were evenly distributed among all size groups, but in contrast there were very few maternal imbalances either <1 Mb or > 10 Mb. Furthermore, a lower proportion of paternal imbalances are LCR mediated (13/71) compared with the maternal imbalances (12/30). We hypothesise that imbalances of maternal origin arise predominantly through NAHR during meiosis, while the majority of those of paternal origin arise through male-specific mechanisms other than NAHR. This suggests that mitotic divisions of testicular germ cells are important in the formation of chromosome imbalances, however, surprisingly we found no association with increased paternal age.

Currently we are testing an hypothesis, originally postulated by Lionel Penrose who suggested, based on evidence provided by dermatoglyphics and grand maternal ages of the mothers of patients with Down syndrome, that at least 10% of young mothers of Down syndrome patients were gonadal mosaics for an additional chromosome 21 and that the majority of these mosaics were conceived as a trisomy 21 in which selective loss of the extra chromosome 21 resulted in a clinically normal individual. It is well established that many Down syndrome individuals who survive to 40 years of age develop Alzheimer’s disease. This has led to the suggestion that mosaicism for chromosome 21 may be causal to the development of Alzheimer’s disease in a proportion of individuals who, while not showing any features of Down syndrome, are trisomy 21 mosaics.

Encouraged by recent developments in non invasive prenatal diagnosis in which very small amounts of fetal DNA is obtained from a maternal blood sample, we are testing DNA from Down syndrome parents for the presence of trisomy 21 mosaicism. Our colleague, Stephanie Sherman, has DNA samples from Down syndrome patients and their parents, in which she has determined the parental origin of the additional chromosome 21. We are currently undertaking a project with her to search for evidence of mosaicism in the DNA of 4 groups of individuals, namely young and old mothers of Down syndrome of maternal origin, fathers of Down syndrome of paternal origin and their spouses.

Initially we tested the DNA using quantitative fluorescent PCR (QF-PCR) in which chromosome 21 specific polymorphic repeat sequences are amplified and quantified. This technique detects levels of mosaicism between 5 to 10%. Our second more powerful approach is to test the samples using techniques developed for non-invasive prenatal diagnosis. Each target can be sequenced to a depth of >100,000 reads and the number of sequences derived from chromosome 21 compared to those obtained from control autosomes. Over-representation of sequences from chromosome 21 will be indicative of mosaicism. We think this technique has the potential to detect mosaicism of 3% or greater, and furthermore it is polymorphism independent.

We recently obtained preliminary results on our first 136 samples using the QF-PCR technique. The tested samples consisted of 47 young and 41 old mothers of Down syndrome of maternal origin, 21 fathers of Down syndrome of paternal origin and 27 spouses of such fathers. We found 6 putative mosaics: 3 among the young mothers, none among the old mothers, 2 among the fathers and 1 among the spouses of the fathers.

If we continue to demonstrate that our techniques can detect mosaicism for chromosome 21 in the DNA from parents of Down syndrome we will extend the study to individuals with Alzheimer’s disease. If we can demonstrate that some individuals with Alzheimer’s disease are trisomy 21 mosaics, it will provide an early test for the condition and thus allow treatment to be instigated at an earlier stage than is currently possible.


Human Development and Health

National and International Responsibilities
Society Memberships

American Society of Human Genetics: Board member (1974-1977); Chairman of the Genetic Services Committee (1974-1978)
Genetical Society of Britain: Board member (1972-1975)
European Society of Human Genetics: Board member (1991-1996)
Clinical Genetics Society: Vice President (1994)
Clinical Genetics Society: President (1995-1997)
British Society of Human Genetics: Board member (1996-1998)

Editorial Boards

Cytogenetics (1962-1970)
Cytogenetics and Cell Genetics (1978-1983)
Journal of Medical Genetics (1969-1971), (1988-2000)
Human Genetics (1978-2000)
American Journal of Human Genetics (1979-1981)
Genetic Epidemiology (1984-1988)
Human Heredity (1986-2000)
Annals of Human Genetics (1995-2000)
Journal of Genetics (1995-present)

Other Professional Activities

American Representative to the International Standing Committee on Cytogenetic Nomenclature (1977-1981), (1981-1986)
Member of the Advisory Committee on Human Cytogenetic Registers Consultant to the Standing Committee on Cytogenetic Nomenclature (1971-1977), (1994)
Member of the National Institute of Health Mammalian Genetics Study Section (1978-1982)
Elected Founder Member of the American Board of Medical Genetics (1979-1982)
Diplomate Clinical Cytogenetics (1987)
Member of the American Cancer Society Scientific Advisory Committee on Cell and Developmental Biology (1987-1988)
NHS National Assessor for Health Service Scientists (Genetics) (1990-present)
Chairman Standing Advisory Committee on Genetics - Royal College of
Pathologists (1991-1994)
Member of the Council of the Royal College of Pathologists (1991-1994)
Member of the Wessex Regional Research & Development Committee (1992-1994)
Member of the Committee on Medical Effects of Radiation in the Environment (1993-1995
Member of the Council of the Royal Society (1993-1995)
Member of the Standing Advisory Committee on Genetics of Clinical Pathology Accreditation Limited (1994-1999)
Member of the Wellcome Trust Genetics Advisory Group (1995-1998)
Chairman of the International Standing Committee on Cytogenetic Nomenclature (1996-2001)
Member of the Medical Advisory Committee of the Sir Jules Thorn Charitable Trust (1996-1997)
Member of the Medical Research Council (1996-1998)
Member of the Council of the Academy of Medical Sciences (1998-2001)
Member of the Wellcome Trust Basic Science Interest Group (1998-2001)
Member of RAE UoA 1 panel Clinical Laboratory Sciences (2001)
Chairman Advisory Committee Breakthrough Generations Study (2004-2006)
Carter Lecturer British Society Human Genetics (2006)
Chairman Scientific and Medical Advisory Committee Jewish Genetic Disorders UK (2010 –present)

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Emeritus Professor Patricia Jacobs
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