Whole Genome Analysis for the Detection of Key Genes in the Polycystic Ovary Syndrome - a Study on Multigenerational Families
1. Working Hypothesis The recent trend in GWA has been the comparison of large numbers of
DNA samples from affected individuals and large pools of unrelated individuals
(Wellcome Trust Case Control Consortium). Whenever the control group came from family
members, the number of patients needed to be sampled has been consistently smaller
(Dempfle a et al 2006; The Japanese Schizophrenia Sib-Pair Linkage Group 2005), due to
less degrees of freedom in the statistical analysis (Chen WM & Abecasis GR 2007).
2. Specific Aims
1. What are the specific informative SNPs, associated with PCOD?
2. What are the specific genes located in the vicinity of these SNPs, which could
contribute to the development of the clinical syndrome? Detailed description of
the proposed research Clinical data collection and patient recruitment Patients
Women will be diagnosed as suffering from PCOD based on the Rotterdam criteria ():
1. Oligo- and/or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism
3. Polycystic ovaries, and exclusion of other aetiologies (congenital adrenal
hyperplasias, androgen-secreting tumours, Cushing's syndrome) Routine testing of
serum levels for the relevant sex hormones will be performed at the 3rd day of the
menstrual cycle. Glucose and insulin levels will be measured at the fasting state.
The individual data collection page is presented as Appendix 1.
Controls Sisters, mothers, fathers, aunts and grandmothers of affected women will be
asked to disclose their relevant clinical history and donate a single blood test for
both DNA extraction and hormonal tests, which will be taken at the 3rd day of
menstruation, where applicable.
The population that is served by Mayanei Hayeshua hospital is characterized by a short
generation interval, due to the mean early age at marriage and the desire to bear
children right after marriage. This should allow the formation of genealogy trees that
are very informative.
through the index cases, and each participant will receive a complete explanation of
possible personal implication of the study results to herself and family (none).
Overall, all included women, patients and family members alike, will be notified as to
the secrecy of the data and its use only for the declared purpose of research. They
will also be made aware that no personal benefit or harm can be derived from this data
to them. In addition, all participants will be informed that if in the future there
will arise a new reason to re-analyze their samples, a specific address will be made to
each and every one of them to obtain a new permission for this use. Upon request each
participant will receive a full explanation of the storage system and the hierarchy of
responsibility for the samples and data security.
3. Compliance to the definition of a feasibility study The funds requested herein are
meant to enable the formation of DNA bank and family trees, which in turn will serve as
the basis for an application to receive the full funding for whole genome analysis,
from larger funding resources. Towards this we have teamed up with the future
participants of a worldwide consortium on this topic (letter of intention from Bart
Fauser, the leading person of this consortium, is attached). Our most pronounced
advantage within the consortium, is the availability of multigenerational families,
members of which we treat in Bnei Brak.
4. Potential Implications to Medicine and contribution of the expected outcome to society
Paving the way for targeted treatment of the problems, associated with PCOS, based on
the clear knowledge of its underlying cause(s).
Observational Model: Family-Based, Time Perspective: Prospective
Izhar Ben-Shlomo, MD
Maaynei Hayeshua Medical Center
Israel: Ministry of Health