REFINEMENT OF LINKAGE OF HUMAN SEVERE COMBINED IMMUNODEFICIENCY (SCIDX1) TO POLYMORPHIC MARKERS IN XQ13

The most commmon form of human severe combined immunodeficiency (SCID) is inherited as an X-linked recessive genetic defect, MIM 300400. The disease locus, SCIDX1, has previously been placed in Xq13.1-q21.1 by demonstration of linkage to polymorphic markers between DXS159 and DXS 3 and by exclusion from interstitial deletions of Xq21.1-q21.3. We rep ort an extension of previous linkage studies, with new markers and a t otal of 25 SCIDX1 families including female carriers identified by non random X chromosome inactivation in their T lymphocytes. SCIDX1 was no nrecombinant with DXS441, with a lod score of 17.96. Linkage relations hips of new markers in the SCIDX1 families were consistent with the li nkage map generated in the families of the Centre d'Etude du Polymorph isme Humain (CEPH) and with available physical map data. The most like ly locus order was (DXS159,DXS153)-DXS106-DXS132-DXS453-(SCIDX1,PGK1, DXS325,DXS347,DXS441)-DXS447-DXS72-DXYS1X-DXS3. The SCIDX1 region now spans approximately 10 Mb of DNA in Xq13; this narrowed genetic locali zation will assist efforts to identify gene candidates and will improv e genetic management for families with SCID.