Human twinning is not linked to the region of chromosome 4 syntenic with the sheep twinning gene FecB

The tendency to dizygotic (DZ) twinning is inherited in both humans and sheep, and a fecundity gene in sheep ( FecB ) maps to sheep chromosome 6, syntenic with human 4q21‐25. Our aim was to see whether a gene predisposing to human DZ twinning mapped to this region. DNA was collected from 169 pairs and 17 sets of 3 sisters (trios) from Australia and New Zealand who had each had spontaneous DZ twins, mostly before the age of 35, and from a replication sample of 111 families (92 affected sister pairs) from The Netherlands. Exclusion mapping was carried out after typing 26 markers on chromosome 4, of which 8 spanned the region likely to contain the human homologue of the sheep FecB gene. We used nonparametric affected sib pair methods for linkage analysis [ASPEX 2.2, Hinds and Risch, 1999]. Complete exclusion of linkage (lod < −2) of a gene conferring a relative risk for sibs as low as 1.5 (λ s  > 1.5) was obtained for all but the p terminus region on chromosome 4. Exclusion in the syntenic region was stronger, down to λ s  = 1.3. We concluded that if there is a gene influencing DZ twinning on chromosome 4, its effect must be minor. © 2001 Wiley‐Liss, Inc.