Jane Gair

JANE L. GAIR - PhD DEFENSE

 

“Genetic Mechanisms of Nondisjunction in Humans”

 

B. Sc., University of British Columbia, 1998

Thursday, July 28, 2005, 9:00 am, Room 200, Graduate Student Centre

Jane Gair - PhD defense- pdf

SUPERVISORY COMMITTEE

Dr. Wendy Robinson (Medical Genetics)

Dr. Fred Dill (Medical Genetics)

Dr. Carolyn Brown (Medical Genetics)

Dr. Ann Rose (Medical Genetics)

Dr. Peter Lansdorp (Hematology)

Dr. Valia Lestou (BC Cancer Agency)

 

 

EXAMINING COMMITTEE

Chair: Dr. Kenny Kwok (Physiology)

Supervisory Committee: Dr. Wendy Robinson (Medical Genetics), Dr. Fred Dill (Medical Genetics), Dr. Carolyn Brown (Medical Genetics)

University Examiners: Dr. Sylvie Langlois (Medical Genetics), Dr. Basil Ho Yuen (Obstetrics)

External Examiner: Dr. Heather McDermid, Department of Biological Sciences University of Alberta, Edmonton, AB.

 

 

ABSTRACT

Missegregation of chromosomes in meiosis, or nondisjunction, occurs relatively frequently in humans, and results in pregnancy loss. There is a correlation with advancing maternal age, but the cause of the dramatic increase of trisomy (the presence of three copies of a chromosome rather then two), seen with age remains unknown. There is evidence to suggest that chronological age is less important than biological age for trisomy risk, and that regardless of their chronological age, some women are at a greater risk of having a trisomic pregnancy after having already experienced one. Several features of chromosomes are associated with aging, such as a decrease in telomere length, an increase in replication asynchrony at loci including centromeres, and an increase in somatic cell trisomy with increasing age. For some chromosomes (15 and 21) an association has also been observed between maternal age, reduced recombination along the chromosome, and risk for nondisjunction. In this project, I have investigated whether or not some women are predisposed to having a trisomic pregnancy. That is, can we predict who will have recurrent trisomy? After analyzing telomere length for an association, no significant decrease in length was seen for women experiencing recurrent trisomy when compared to control women. There was a trend, however, towards longer telomeres in women with a “good” reproductive history (children after 37 years of age) compared to women with a “poor” reproductive history (trisomy and/or recurrent trisomy). As well, although there was no significant increase in replication asynchrony in trisomy mothers as a group, the younger mothers (<35 years old) of trisomy had increased replication asynchrony when compared to controls of the same age. The relationship between recombination and nondisjunction has been well established and my studies of chromosome 15 confirmed that decreased recombination is associated with meiosis I errors and increased recombination is associated with meiosis II errors. A family with an apparent inherited predisposition to missegregation of chromosome 21 seemed the ideal family in which to study possible genetic mechanisms of nondisjunction. Although nothing conclusive could be determined to be causing their segregation problems, a cryptic rearrangement involving the centromere of chromosome 21 is the most likely explanation. Finally, telomere length was not found to be shortened in children conceived through ICSI, something that could predispose them to somatic nondisjunction.

 

 

PUBLICATIONS

Bourguet, D, Gair, J, Mattice, M and M Whitlock. Genetic recombination and adaptation to fluctuating environments: selection for geotaxis in Drosophila

melanogaster. Heredity. 2003 Jul;91(1):78-84.

 

Robinson, WP, Peñaherrera, MS, Gair, J, Hatakeyama, C, and S Ma. Research Letter: X-chromosome inactivation and telomere size in newborns resulting from intracytoplasmic sperm injection. AJMG. 2005.

 

 

PRESENTATIONS

Poster presentation at ASHG in Toronto – October 26-30, 2004 – “Recurrent Trisomy 21: Four Cases in Three Generations.”

 

Talk given at 15th Annual Chromosome Conference in London, England – September 2004 – “Recurrent Trisomy 21: Four cases in three generations.”

 

Poster presentation at ASHG in Los Angeles – November 4-8, 2003 – “Is Telomere Length Associated with Trisomy Risk in Humans?”

 

Talk given at Peter Wall Conference at UBC – May 2003 – “Telomeres, Replication Timing and Methylation – A Role in Trisomy Risk?”

 

Poster presentation at ASHG in San Diego – October 2001 – “Distribution of

Exchanges in Chromosome 15 Nondisjunction.”

 

Poster presentation at ASHG (American Society of Human Genetics) in Philadelphia – October 3-7, 2000 – “Proximal Deletion Breakpoints are Sites of High Homologous Recombination.”

 

 

AWARDS

Ph.D. Tuition Fee Award Sept. 2003

University of BC Graduate Fellowship Sept. 2002

University of BC Graduate Fellowship Sept. 2000

 

 

GRADUATE STUDIES

Field of Study: Cytogenetics and Nondisjunction in Meiosis in Humans

 

Courses:

MEDG520 Advanced Human Molecular Genetics Dr. C. Brown

MEDG530 Advanced Human Genetics Dr. J. Friedman

MEDG540 Seminar in Medical Genetics Dr. F. Dill & Dr. C. Brown

MEDG525 Human Genetics Population Level Dr. W. Robinson

MEDG535 Introduction to Genetics and Ethics Dr. M. Burgess & Dr. L. Arbour

GENE502 Genetics Dr. A. Rose

Jane Gair - PhD defense- pdf