Genetic modelling of dizygotic twinning in pedigrees of spontaneous dizygotic twins.
The inheritance of spontaneous dizygotic (DZ) twinning was investigated in 1,422 three-generation pedigrees ascertained through mothers of spontaneous DZ proband twins. DZ twinning was modelled as a trait expressed only in women. The penetrance was modelled first as a parity independent and secondly as parity dependent. The observed frequencies of maternal and paternal grandmothers with DZ twins differed significantly from the expectations under an X-linked mode of inheritance. Complex segregation analysis showed that the parity-independent phenotype of "having DZ twins" was consistent with an autosomal monogenic dominant model, with a gene frequency of 0.035 and a female-specific lifetime penetrance of 0.10. Recessive, polygenic, and sporadic models were rejected. The autosomal dominant model revealed a strong robustness against a changing population prevalence and the loss of information due to the presence of same-sexed twin pairs of unknown zygosity. When DZ twinning was modelled as a parity dependent trait, the data were compatible with an autosomal dominant model with a gene frequency of 0.306 and a penetrance of 0.03 per birth for female gene carriers.
Meulemans
W J
WJ
Center for Human Genetics, Catholic University of Leuven, Belgium.
Lewis
C M
CM
Boomsma
D I
DI
Derom
C A
CA
Van den Berghe
H
H
Orlebeke
J F
JF
Vlietinck
R F
RF
Derom
R M
RM
D016000:Cluster Analysis; D005260:Female; D005306:Fertilization; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D015995:Prevalence; D014429:Twins, Dizygotic / Q000235:genetics* / Q000706:statistics & numerical data