Haplotypes Carrying BRCA1 Mutations Found Repeatedly in the Dutch Population

These data were published in part by Peelen et al. (1997) and Petrij-Bosch et al. (1997)
Last modified on December 3, 1997 by Peter Devilee

OriginMutationTimes found
Non-Dutch185delAG >10
Dutch2804delAA > 20
genomic deletion exon 13 (3,835 bp)
genomic deletion exon 22 (510 bp)
1410insT > 5
1438delT < 5


Human genomic DNA was isolated from 20ml EDTA or heparinized blood samples (Miller et al. 1988). Eight polymorphic microsatellite markers located on chromo some 17q spanning a 5.7 cM interval including BRCA1 were used in a radioactive PCR under conditions described elsewhere (Cornelis et al. 1995). From centromere to telomere, the order reported in the Genome Data Base (GDB) is as follows: D17S250, THRA1, D17S1321, D17S855, D17S1322, D17S1323, D17S1327, D17S579. Primer sequences to amplify these markers can be retrieved online from the GDB. A physical map for a number of these markers has been resolved (Neuhausen et al. 1996), and these distances (in kb) are:


D17S1323 is in intron 13 of BRCA1, D17S1322 in intron 19, and D17S855 in intron 20 (Smith et al. 1996). The sex-average genetic distance between THRA1 and D17S579 is 3.2 cM. We used DNA-sample CEPH1347-02 as a reference to size alleles in bp.

References cited

Cornelis R, Vasen H, Meijers-Heijboer H, Ford D, Van Vliet M, Van Tilborg A, Cleton F, Klijn J, Menko F, Meera Khan P, Cornelisse C, Devilee P (1995) Age at diagnosis as an indicator of eligibility for BRCA1 DNA-testing in familial breast cancer. Hum. Genet. 95: 539-544

Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16: 1215

Neuhausen SL, Mazoyer S, Friedman L, Stratton M, Offit K, Caligo A, Tomlinson G, Cannon-Albright L, Bishop T, Kelsell D, Solomon E, Weber B, Couch F, Struewing J, Tonin P, Durocher F, Narod S, Skolnick MH, Lenoir G, Serova O, Ponder BAJ, Stoppa-Lyonnet D, Easton D, King M-C, Goldgar DE (1996) Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am.J.Hum.Genet. 58: 271-280

Peelen, T., Van Vliet, M., Petrij-Bosch, A., Mieremet, R., Szabo, C., Van den Ouweland, A.M.W., Hogervorst, F., Brohet, R., Ligtenberg, M.J.L., Teugels, E., Van der Luijt, R., Van der Hout, A.H., Gille, J.J.P., Pals, G., Jedema, I., Olmer, R., Van Leeuwen, I., Newman, B., Plandsoen, M., Van der Est, M., Brink, G., Hageman, S., Arts, P.J.W., Bakker, M.M., Wil lems, H.W., Van der Looij, E., Neyns, B., Bonduelle, M., Jansen, R., Oosterwijk, J.C., Sijmons, R., Smeets, H.J.M., Van Asperen, C.J., Meijers-Heijboer, H., Klijn, J.G.M., De Greve, J., King, M.C., Menko, F.H., Brunner, H.G., Halley, D., Van Ommen, G.-J.B., Vasen, H.F.A., Corne lisse, C.J., Van 't Veer, L.J., De Knijff, P., Bakker, E., Devilee, P. (1997) A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. Am. J. Hum. Genet. 60: 1041-1049.

Petrij-Bosch, A., Peelen, T., Van Vliet, M., Van Eijk, R., Olmer, R., Drusedau, M., Hogervorst, F.B.L., Hageman, S., Arts, P.J.W., Ligtenberg, M.J.L., Meijers-Heijboer, H., Klijn, J.G.M., Vasen, H.F.A., Cornelisse, C.J., Van 't Veer, L.J., Bakker, E., Van Ommen, G.-J.B., Devilee, P. (1997) BRCA1 genomic deletions are major founder mutations in Dutch breast cancer families. Nature Genet. 17: 341-342

Smith TM, Lee MK, Szabo CI, Jerome N, Mceuen M, Taylor M, Hood L, King M-C (1996) Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1. Genome Res. 6: 1029-1049