Group Title: Cerebrospinal Fluid Research 2004, 1 (Suppl 1): S30
Title: Linkage analysis for hydrocephalus in the LEW/Jms rat strain
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Title: Linkage analysis for hydrocephalus in the LEW/Jms rat strain
Series Title: Cerebrospinal Fluid Research 2004, 1 (Suppl 1): S30
Physical Description: Archival
Creator: Jones H
Totten C
Mayorga D
Publication Date: 12/24/2004
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Bibliographic ID: UF00100237
Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: Open Access: http://www.biomedcentral.com/info/about/openaccess/

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Cerebrospinal Fluid Research



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Linkage analysis for hydrocephalus in the LEW/Jms rat strain
H Jones*, C Totten and D Mayorga


Address: Department of Pharmacology, University of Florida, Gainesville, Florida, USA
Email: H Jones* hjones@college.med.ufl.edu
* Corresponding author



from 48th Annual Meeting of the Society for Research into Hydrocephalus and Spina Bifida
Dublin, Ireland, 23-26 June 2004
Published: 23 December 2004
Cerebrospinal Fluid Research 2004, I (Suppl I):S30 doi: 10.1 186/1743-8454- I-S I-S30
This article is available from: http://www.cerebrospinalfluidresearch.com/content/ I/SI/S30


The Lew/Jms rat is an inbred strain with severe inherited
hydrocephalus. The hydrocephalus starts in late gestation
and occurs twice as often in males as females. The aim of
this study was to locate the genetic loci linked to the
hydrocephalus on the rat genome. Methods: Progeny were
generated from two different backcrosses with Fischer
F344 rats: one bred using male LEW/Ims rats for each pair-
ing and the other using female LEW/Ims rats. Tissue was
collected for DNA extraction and the brains were fixed
and sliced for measurement of ventricular dilatation.
Quantitative trait locus (QTL) mapping is a method
whereby genetic loci for a quantitative trait are localized
to specific chromosomal regions. A two-stage genome
scan was performed on the hydrocephalic progeny and
the same number of non-hydrocephalic progeny from
both crosses, using a panel of DNA microsatellite markers
previously determined to be polymorphic between the
LEW/Ims and F344 strains. Linkage of chromosomal
regions to hydrocephalus was determined from statistical
association between genotype and phenotype (X2 and
LOD score). Results: The backcross using male LEW/Ims
rats resulted in 918 progeny of which 167 had severe or
mild hydrocephalus (18.2%) and there were significantly
more affected males than females (109:58, P < 0.001). The
backcross using female rats resulted in a total of 910 rats
of which 182 had severe or mild hydrocephalus (19.9 %).
Again, there were more males than females with hydro-
cephalus (102:80) but it was not significant. The mean
severity of ventricular dilatation was significantly different
for the two crosses (0.58 0.01, 0.61 0.01, P < 0.05),
and both groups had significantly smaller ventricles than
the parental LEW/Ims strain (0.66 0.01, P < 0.01 and
0.05). QTL mapping produced different results for the two
crosses. The backcross using two male LEW/Ims rats
showed possible linkage on chromosomes 1, 5, 17 and
19. None reached the full significance required for a
genome-wide scan and only Chrs 5 and 19 were sugges-


ed Central

......ce.


tive for significance. The backcross using two female rats
showed possible linkage on Chrs 2, 4, and 17. There was
full significance on Chr 2 with a LOD score of 3.91. Com-
bining the data for both crosses also resulted in a locus
that was close to full significance on Chr 17, LOD = 2.71.
The linkage data for Chrs 1 and 2 showed sex specificity
when analysed separately for males and females.
Although not fully x-linked, investigations are ongoing to
determine if there is partial linkage with the X chromo-
some. It is concluded that the expression of hydrocepha-
lus in this strain is dependent on different genetic loci for
male and female rats.


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