Genome-wide linkage in three Dutch families maps a locus for abdominal aortic aneurysms to chromosome 19q13.3.
OBJECTIVE
Elucidation of the genetic background of familial abdominal aortic aneurysm (AAA) suggests a genetic etiology.


RESULTS
We carried out a genome-wide scan in three Dutch families with four or five affected siblings. Suggestive loci were further studied by subsequent fine mapping of the locus performed in 101 affected sib-pairs. The genome-wide scan was performed with 400 DNA markers and results were given as non-parametric, multipoint linkage scores (NPL). We observed a suggestive linkage for AAA (NPL score 3.25 at D19S902, 72.72 cM) on chromosome 19q in the three families. After fine mapping on chromosome 19, the NPL score became nominal in the 101 affected sib-pairs. A separate analysis of the three families with fine mapping revealed a peak with significant evidence for linkage (NPL score 3.95 at D19S904, 78.08 cM) on chromosome 19q. This peak was situated to the right compared to the region found in a previously published article for familial AAA on chromosome 19q.


CONCLUSIONS
Our results identified a candidate locus in three Dutch families with AAA at chromosome 19q13.3. Separate analysis of these three families provides evidence for genetic heterogeneity.
Van Vlijmen-Van Keulen
C J
CJ
Institute for cardiovascular research, VU university Medical Center, Amsterdam, The Netherlands. cj.vanvlijmen@vumc.nl
Rauwerda
J A
JA
Pals
G
G
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D019901:Locus Control Region / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010375:Pedigree; D016133:Polymerase Chain Reaction; D035781:Siblings
D004247:DNA