Dizygotic twinning is not linked to variation at the alpha-inhibin locus on human chromosome 2.
Natural multiple pregnancy in women leading to dizygotic (DZ) twins is familial and varies across racial groups, suggesting a genetic predisposition. Mothers of DZ twins have a higher incidence of spontaneous multiple ovulation and elevated FSH concentrations. FSH release is controlled by feedback of inhibin peptides from the ovary, and immunization against inhibin alpha-subunit results in an increased ovulation rate in animals. The inhibin alpha-subunit is therefore a candidate gene for mutations that may increase the frequency of DZ twinning. Restriction digests of a PCR product from exon 1 with the enzyme SpeI detects a C/T polymorphism at bp 128 with two alleles of 447 and 323/124 bp. The polymorphism was typed in 1,125 individuals from 326 pedigrees with 717 mothers of spontaneous DZ twins. The alpha-inhibin locus mapped within 3 centimorgans of D2S164, and linkage with DZ twinning was excluded [decimal log odds ratio (LOD) score, -2.81 at theta = 0]. There was complete exclusion of linkage (LOD, less than -2) of a gene conferring relative risk 1.8 (lambdas, >1.8) across the chromosome, except at the p-terminus region and a small peak (maximum LOD score, 0.6) in the region of D2S151-D2S326. Analysis using either recessive or dominant models excluded linkage with DZ twinning in this population (LOD score, less than -2.5) across chromosome 2. We conclude that dizygotic twinning is not linked to variation in the alpha-inhibin locus. The results also suggest that mutations in other candidates on chromosome 2, including the receptor for FSH and the betaB-inhibin subunit (INHBB) cannot be major contributors to risk for DZ twinning.
Montgomery
G W
GW
Genetic Epidemiology Laboratory, Queensland Institute of Medical Research and Joint Genetics Program, University of Queensland, Brisbane, Australia. grantM@qimr.edu.au
Duffy
D L
DL
Hall
J
J
Haddon
B R
BR
Kudo
M
M
McGee
E A
EA
Palmer
J S
JS
Hsueh
A J
AJ
Boomsma
D I
DI
Martin
N G
NG
D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D016678:Genome; D006801:Humans; D007265:Inhibins / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D011962:Receptors, FSH / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014429:Twins, Dizygotic / Q000235:genetics*
D011962:Receptors, FSH; D007265:Inhibins; D004247:DNA