Tmu. Wagner et al., Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations, HUM MOL GEN, 8(3), 1999, pp. 413-423
The aim of this study was to evaluate the prevalence of simple sequence var
iation in the BRCA2 gene. To this end, 71 breast and breast-ovarian cancer
(HBC/HBOC) families along with 95 control individuals from a wide range of
ethnicities were analyzed by means of denaturing high-performance liquid ch
romatography (DHPLC) and direct sequence analysis. In the coding (10 257 bp
) and non-coding (2799 bp) sequences of BRCA2, 82 sequence variants were id
entified. Three different, apparently disease-associated BRCA2 mutations we
re found in six HBC/HBOC families (8%): two splice site mutations in intron
s 5 and 21, and one frameshift mutation in exon 11, In the coding region, 5
3 simple sequence variants were found: 35 missense mutations, one 2 bp dele
tion (CT) resulting in a stop at codon 3364, one nonsense mutation with a s
top at codon 3326, one deletion of a complete codon (AAA) resulting in the
loss of leucine, and 15 silent mutations, In the non-coding region, 26 poly
morphisms were detected. Of the 79 sequence variants that were not obviousl
y disease-associated, eight were detected only in HBC/HBOC families. The re
maining 71 variants were identified in both HBC/HBOC families and control i
ndividuals. Sixty three sequence variants (80%) were specific for a contine
nt, Forty two percent (33 out of 79) of the sequence variants were detected
exclusively in Africa, though only 13% of the 332 chromosomes screened wer
e of African origin. Our data indicate that, in BRCA2, simple sequence vari
ation is frequent [in the coding region 1 in 194 bp (theta = 2.2 x 10(-4)),
and in the non-coding region 1 in 108 bp (theta = 4.4 x 10(-4)), respective
ly],