Variation in BMPR1B, TGFRB1 and BMPR2 and control of dizygotic twinning.

Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ß receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning.

The Netherlands Twin Register biobank: a resource for genetic epidemiological studies.

In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am, fasting blood and morning urine samples were collected.

A genome wide linkage scan for dizygotic twinning in 525 families of mothers of dizygotic twins.

Background: The tendency to conceive dizygotic (DZ) twins is a complex trait influenced by genetic and environmental factors. To search for new candidate loci for twinning, we conducted a genome-wide linkage scan in 525 families using microsatellite and single nucleotide polymorphism marker panels.

Methods And Results: Non-parametric linkage analyses, including 523 families containing a total of 1115 mothers of DZ twins (MODZT) from Australia and New Zealand (ANZ) and The Netherlands (NL), produced four linkage peaks above the threshold for suggestive linkage, including a highly suggestive peak at the extreme telomeric end of chromosome 6 with an exponential logarithm of odds [(exp)LOD] score of 2.

Body composition, smoking, and spontaneous dizygotic twinning.

Objective: To examine differences in body composition and smoking between mothers of spontaneous monozygotic and dizygotic twins, while taking into account maternal age, gravidity, and educational attainment.

Design: Retrospective cohort study.

Setting: The Netherlands Twin Register.

Familial twinning and fertility in Dutch mothers of twins.

We studied twinning and fertility indices in mothers with spontaneous monozygotic (MZ) and dizygotic (DZ) twins and in mothers who conceived their twins after the use of assisted reproduction techniques (ART). Participants in this study consisted of 8,222 and 5,505 women with spontaneous DZ and MZ offspring and 4,164 and 250 women with ART DZ and MZ twin pairs, respectively. Women were compared with respect to the number of sibs and offspring, the presence of other relatives with twins and the time it took to conceive the twins.

Mode of conception of twin pregnancies: willingness to reply to survey items and comparison of survey data to hospital records.

Based on results from a survey study in a sample of Australian parents of twins, Raj and Morley (2007) reported that questions concerning the mode of conception of twins may be offensive to parents. We looked at the willingness to reply to questions about mode of conception of twin pregnancies in a large survey study that was completed by 20,150 mothers of twins from the Netherlands Twin Registry. Data collection took place in 2005/2006.

Dizygotic twinning.

The tendency to conceive spontaneous dizygotic (DZ) twins is a complex trait with important contributions from both environmental factors and genetic disposition. Twins are relatively common and occur on average 13 times per 1000 maternities, though the twinning frequency varies over time and geographic location. This variation is mostly attributed to the differences in DZ twinning rate, since the monozygotic twinning rate is relatively constant.

Novel variants in growth differentiation factor 9 in mothers of dizygotic twins.

Context: Genes from the ovarian bone morphogenetic signaling pathway (GDF9 and BMP15) are critical for normal human fertility. We previously identified a deletion mutation in GDF9 in sisters with spontaneous dizygotic (DZ) twins, but the prevalence of rare GDF9 variants in twinning families is unknown.

Objective: The objective was to evaluate the frequency of rare variants in GDF9 in families with a history of DZ twinning.

Profiling gene expression in whole blood samples following an in-vitro challenge.

Genomics tools (gene- and protein-expression studies) can be used to find possible target genes involved in a quantifiable trait or disease state. However in many instances, cells and tissues directly involved in the trait's expression, for example, brain tissue, are not amenable for gene expression analysis. Whole blood cells share a molecular make-up for cellular communication and gene regulation systems with many other cell types, for example, neuronal cells, and have the advantage of being very accessible for gene profiling.

Genetics of dizygotic twinning: a feasibility study for a biobank.

To locate the genes that make a substantial contribution to variation in natural dizygotic twinning in humans, large-scale studies are needed. New studies should not stop at DNA genotyping, but collect material that allow gene-expression analysis, transcriptomics, proteomics and endocrinology. In this article we describe a pilot study to examine the feasibility, effectiveness and logistics of large-scale nationwide sample collection in Dutch families in which two or more sisters have given birth to spontaneous dizygotic twins.