The procedure starts with the selected sequences used as seed for Seed Linkage search in UniProtKB.
This comprises the largest post-BRCA1/2 linkage search effort in breast cancer families in the world to date.
Thus, this collaboration has now collected 78 families for a linkage search, and several preliminary hints for linkage are currently being pursued further.
In the initial genome-wide linkage search, marker D8S258 generated the highest two-point LOD score of 2.5 at theta = 0.
A genome-wide linkage search was performed on this family, leading to a significant linkage (Lod score = 12.4) between the chromosomal region 6q22.3-q24 and increased HbF expression [ 14, 15].
However, a linkage search carried out jointly by David Goldgar and Mike Stratton (Institute of Cancer Research, Belmont, Sutton, UK) in a subset of approximately 50 such BCLC families, which were carefully selected for not being due to BRCA1 or BRCA2, has remained negative so far.
A recent genome-wide linkage search on 237 TGCT pedigrees, the largest series of TGCT families examined to date, identified several 'regions of interest' on chromosomes 2p33, 3p12, 3q26, 12q13 q21, 18q21 q23 and Xq27.
We carried out a genome-wide linkage search using Affymetrix GeneChip® Human Mapping 250K Sty Arrays according to the manufacturer's protocol (http://www.affymetrix.com) in six affected members and two unaffected members of the family.
The first genome-wide linkage search in familial POI identified a region on chromosome 5q14.1 q15 that may harbour a novel POI susceptibility gene (Oldenburg et al., 2008), and a recent GWAS identified ADAMTS19 (5q31) as a possible candidate gene for POI (Knauff et al., 2009).
This would be a substantial undertaking (at least four-fold larger than the current linkage searches) but would be achievable with international collaboration.
