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 she ep, and a fecundity gene in sheep (FecB) maps to sheep chromosome 6, synten ic with human 4q21-25. Our aim was to see whether a gene predisposing to hu man 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 h ad spontaneous DZ twins, mostly before the age of 35, and from a replicatio n sample of 111 families (92 affected sister pairs) from The Netherlands. E xclusion mapping was carried out after typing 26 markers on chromosome 4, o f which 8 spanned the region Likely to contain the human homologue of the s heep 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 (<l ambda>(s) > 1.5) was obtained for all but the p terminus region on chromoso me 4. Exclusion in the syntenic region was stronger, down to lambda (s) = 1 .3. We concluded that if there is a gene influencing DZ twinning on chromos ome 4, its effect must be minor. (C) 2001 Wiley-Liss, Inc.