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| PMID |
|
|
| 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 |
| 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. 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 |
| 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. The objective was to evaluate the frequency of rare variants in GDF9 in families with a history of DZ twinning. 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 |
| 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. The objective was to evaluate the frequency of rare variants in GDF9 in families with a history of DZ twinning. 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. 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 |
| 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. The objective was to evaluate the frequency of rare variants in GDF9 in families with a history of DZ twinning. 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. 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%). 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| 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 |
|
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| 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 |
|
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| KEYWORDS |
|
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| 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 |
|
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|
