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Genetic loci for ventricular dilatation in the LEW/Jms rat with fetal-onset hydrocephalus are influenced by gender and genetic background

DOI: 10.1186/1743-8454-2-2

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Abstract:

An F1 backcross was made to the parental LEW/Jms strain from a cross with non-hydrocephalic Fischer 344 rats. BC1 rats were generated for two specific crosses: the first with a male LEW/Jms rat as parent and grandparent, [(F × L) × L], designated B group, and the second with a female LEW/Jms rat as the parent and grandparent [L × (L × F)], designated C group. All hydrocephalic and a similar number of non-hydrocephalic rats from these two groups were genotyped with microsatellite markers and the data was analyzed separately for each sex by MAPMAKER.The frequency of hydrocephalus was not significantly different between the two groups (18.2 and 19.9 %), but there was a significant excess of males in the B group. The mean severity of hydrocephalus, measured as the ventricle-to-brain width ratio, was ranked as B group < C group < LEW/Jms. For the both rat groups, there were several chromosomes that showed possible regions with association between phenotype and genotype significant at the 5% or 1.0% level, but none of these had significant LOD scores. For the C group with a female LEW/Jms parent, there was a fully significant locus on Chr2 with a LOD score of 3.81 that was associated almost exclusively with male rats. Both groups showed possible linkage on Chr17 and the data combined produced a LOD score of 2.71, between suggestive and full significance. This locus was largely associated with male rats with a LEW/Jms male parent.Phenotypic expression of hydrocephalus in Lew/Jms, although not X-linked, has a strong male bias. One, and possibly two chromosomal regions are associated with the hydrocephalus.Fetal hydrocephalus occurs in humans from causes such as intraventricular hemorrhage and intrauterine infections, but in other cases the cause cannot be identified with certainty. Epidemiological studies provide evidence that hydrocephalus has a genetic component [1-3], although only one inherited form, X-linked hydrocephalus, has been characterized at the molecular level

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