Human Molecular Genetics, Vol 8, 915-922, Copyright © 1999 by Oxford University Press
PJ Fisher, D Turic, NM Williams, P McGuffin, P Asherson, D Ball, I Craig, T Eley, L Hill, K Chorney, MJ Chorney, CP Benbow, D Lubinski, R Plomin and MJ Owen
General cognitive ability (g), which is related to many aspects of brain
functioning, is one of the most heritable traits in neuroscience. Similarly
to other heritable quantitatively distributed traits, genetic influence on
g is likely to be due to the combined action of many genes of small effect
[quantitative trait loci (QTLs)], perhaps several on each chromosome. We
used DNA pooling for the first time to search a chromosome systematically
with a dense map of DNA markers for allelic associations with g. We
screened 147 markers on chromosome 4 such that 85% of the chromosome were
estimated to be within 1 cM of a marker. Comparing pooled DNA from 51
children of high g and from 51 controls of average g, 11 significant QTL
associations emerged. The association with three of these 11 markers (
D4S2943, MSX1 and D4S1607 ) replicated using DNA pooling in independent
samples of 50 children of extremely high g and 50 controls. Furthermore,
all three associations were confirmed when each individual was genotyped
separately ( D4S2943, P = 0. 00045; MSX1, P = 0.011; D4S1607, P = 0.019).
Identifying specific genes responsible for such QTL associations will open
new windows in cognitive neuroscience through which to observe pathways
between genes and learning and memory.
ARTICLES
DNA pooling identifies QTLs on chromosome 4 for general cognitive ability in children
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff CF4 4XN, UK.
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