Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
16954162
TITLE
Novel variants in growth differentiation factor 9 in mothers of dizygotic twins.
ABSTRACT
CONTEXT NlmCategory: BACKGROUND
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 NlmCategory: OBJECTIVE
The objective was to evaluate the frequency of rare variants in GDF9 in families with a history of DZ twinning.
DESIGN AND SUBJECTS NlmCategory: METHODS
We recruited 3450 individuals from 915 DZ twinning families (1693 mothers of twins) and 1512 controls of Caucasian origin. One mother of DZ twins was selected from 279 of the 915 families, and a DNA sample was screened for rare variants in GDF9 using denaturant HPLC. Variants were confirmed by DNA sequencing and genotyped in the entire sample by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry.
RESULTS NlmCategory: RESULTS
We found two novel insertion/deletions (c.392-393insT, c.1268-1269delAA) and four missense alterations in the GDF9 sequence in mothers of twins. Two of the missense variants (c.307C > T, p.Pro103Ser and c.362C > T, p.Thr121Leu) were located in the pro-region of GDF9 and two (c.1121C > T, p.Pro374Leu and c.1360C > T, p.Arg454Cys) in the mature protein region. For each variant, the frequencies were higher in cases compared with controls. The proportion of mothers of DZ twins carrying any variant (4.12%) was significantly higher (P < 0.0001) than the proportion of carriers in controls (2.29%).
CONCLUSION NlmCategory: CONCLUSIONS
We describe new variants in the GDF9 gene that are significantly more common in mothers of DZ twins than controls, suggesting that rare GDF9 variants contribute to the likelihood of DZ twinning.
DATE PUBLISHED
2006 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2006/09/05
pubmed 2006/09/07 09:00
medline 2007/01/16 09:00
entrez 2006/09/07 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Palmer JS Palmer James S JS Molecular Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia.
Zhao ZZ Zhao Zhen Zhen ZZ
Hoekstra C Hoekstra Chantal C
Hayward NK Hayward Nicholas K NK
Webb PM Webb Penelope M PM
Whiteman DC Whiteman David C DC
Martin NG Martin Nicholas G NG
Boomsma DI Boomsma Dorret I DI
Duffy DL Duffy David L DL
Montgomery GW Montgomery Grant W GW
INVESTIGATORS
JOURNAL
VOLUME: 91
ISSUE: 11
TITLE: The Journal of clinical endocrinology and metabolism
ISOABBREVIATION: J. Clin. Endocrinol. Metab.
YEAR: 2006
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0021-972X
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: J Clin Endocrinol Metab
COUNTRY: United States
ISSNLINKING: 0021-972X
NLMUNIQUEID: 0375362
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
HD042157 NICHD NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Bone Morphogenetic Protein 15
Control Groups
Female
Gene Deletion
Gene Frequency
Genetic Testing
Genetic Variation
Growth Differentiation Factor 9
Humans
Intercellular Signaling Peptides and Proteins genetics
Mothers genetics
Pedigree genetics
Polymorphism, Genetic genetics
Pregnancy genetics
Twins, Dizygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 BMP15 protein, human
0 Bone Morphogenetic Protein 15
0 GDF9 protein, human
0 Growth Differentiation Factor 9
0 Intercellular Signaling Peptides and Proteins
OTHER ID's