Twinning Genetics Study
Study Code:TG
Sample:Mothers of non-identical twins, their parents and siblings
Start Date:Jan.1995
Status:In progress
Contact:Anjali Henders
More Info:QIMR only


Contents

 


About the Study

This is an international study that is being conducted in Australia, New Zealand and the Netherlands. The overall purpose of this research is to find the gene or genes responsible for the tendency to conceive non-identical twins. By interviewing and obtaining blood samples for gene analysis from sisters who have both had non-identical twins, and their parents or siblings, we hope to understand more about how specific genes influence multiple ovulation. It is also hoped that this study will contribute to our understanding of the mechanisms of female fertility and infertility, which will in turn lead to the development of diagnostic tests; the design of better treatments for infertility and open up new strategies for controlling fertility.


Participants

Sisters with non-identical twins are asked to complete a short telephone interview and provide a small blood sample. The interview takes about 25 minutes and includes questions about the twins and the family history of non-identical twinning together with confidential personal details regarding pregnancy, birth, gynaecological, menstrual and medical history. With written consent, the sisters DNA will be extracted from their samples for genetic analysis.

We will also ask permission to contact the parents and possibly the brothers and sisters of the mothers of twins, to request their donation of a small blood sample. If we cannot collect blood samples from both parents, we can often work out their genes by analysing the blood of their brothers and sisters.

Permission to contact any other close family members who have had non-identical twins is also sought - so that may be invited to participate in our research. If you are interested in participating in this research please contact the project coordinator Thanuja Gunasekera  on 07-3362 0195 or free call 1800 257 179.


Progress to date

In our early research we asked some Mothers of DZ twins to take part in studies where ovarian ultrasound scans were taken at various times of the month. From this work we were able to show that mothers who have already had DZ twins (MODZTs - Mothers Of DZ Twins) seem to develop more large follicles each month compared with women who have not had DZ twins. Some mothers of twins have also participated in studies investigating the hormonal profiles. Results vary between studies and suggest there may be different hormonal pathways leading to multiple ovulation. An alternative explanation is that differences within the ovary lead to increased twinning. In our research we are interested in the causes of spontaneous multiple pregnancy, so we exclude cases of assisted reproduction (Clomid, IVF-ET, GIFT etc).

Studies in animal models have recently established an important pathway within the ovary regulating follicle development and twinning. Variation in at least three genes from this pathway can increase twinning. We have begun to analyze the same genes to see whether variation in these genes in women also contributes to increases in spontaneous DZ twins. One gene is a growth factor located on the X chromosome. Mutations in this gene in sheep are associated with both twinning and infertility. We found no mutations in this growth factor in families with a high frequency of twins. We are currently looking to see if more subtle variation might contribute to twinning. The second gene is a receptor located on chromosome 4. Our data does not support a role for this gene in human DZ twinning, although variation with small effects has not been excluded.

Finding genes in humans that contribute to twinning would lead to fundamental new insights into the mechanisms of female fertility and may have practical implications for controlling fertility and infertility.

Together with our collaborators in the Netherlands and New Zealand we are moving towards our target of 1,000 sister pairs. To date we have collected interview data and blood samples from 441 sister pairs and their families.

International collaboration

This study is an international collaboration with Professor Dorret Boomsma and Associate professor Gonneke Willemsen at the Free University, Amsterdam. The international collaboration is based around the use of similar biological measures by the two teams to investigate the genetic basis of non-identical twinning.

 

Dorret Boomsma

Position

   

Professor

Department

   

Biological Psychology

Address

   

Van der Boechorststraat 1, 1081 BT Amsterdam

Room

   

2B-41

Phone

   

+31 (0)20 598 8787

 

 

Gonneke Willemsen

 

Position

   

Associate professor

Department

   

Biological Psychology

Address

   

Van der Boechorststraat 1, 1081 BT Amsterdam

Room

   

2C-17

Phone

   

+31 (0)20 598 8952

 

 

QIMR Logo

Queensland Institute of Medical Research

Freelogo

TNO ACLS Preventie en zorg

Zernikedreef 9

2333 CK Leiden

The Netherlands

 

Phone: *31-071 5181236

Fax: *31-071 5181901

 


 


Publications

  • Montgomery GW, Zhao ZZ, Marsh AJ, Mayne R, Treloar SA, James MR, Martin NG, Boomsma DL, Duffy DL (2004) A Deletion Mutation in GDF9 in Sisters with Spontaneous DZ Twins. Twin Research 7: 548-555
  • Hoekstra C, Meijer P, Kluft C, Heutink P, Smit G, de Geus E, Smit JH, van Bruggen A, Montgomery GW, Boomsma DI (2004) Genetics of Dizygotic Twinning: A Feasibility Study for a Biobank. Twin Research 7: 556-563
  • Montgomery, G.W., Zhao, Z.Z., Morley, K.I., Marsh, A.J., Boomsma, D.L., Martin, N.G. and Duffy, D.L. (2003). DZ twinning is not associated with methylene-tetra-hydrofolate reductase haplotypes. Human Reproduction 18: 1-5.
  • Duffy D, Montgomery G, Treloar S, Birley A, Kirk K, Boomsma D, Beem L, de Gues E, Slagboom E, Knighton J, Reed P and Martin N (2001) IBD sharing around the PPARG locus is not increased in dizygotic twins or their mothers Nature Genetics 28 316
  • Duffy DL, Montgomery GW, Hall J, Mayne C, Healey SC, Brown J, Boomsma DI and Martin NG (2001) Human twinning is not linked to the region of chromosome 4 syntenic with the sheep twinning gene FecB. American Journal of Medical Genetics 100 182-186
  • Montgomery GW, Duffy DL, Hall J, Kudo M, Martin NG and Hsueh AJ (2001) Mutations in exon 10 of the follicle-stimulating hormone receptor are not a common cause of familial dizygotic twinning The Lancet 357 773-774
  • GW Montgomery, DL Duffy, J Hall, BR Haddon, M Kudo, EA McGee, JS Palmer, AJ Hsueh, DI Boomsma, NG Martin (2000). Dizygotic twinning is not linked to variation at the a-Inhibin locus on human chromosome 2. Journal of Clinical Endocrinology & Metabolism, 85 (9), 3391-3395.