Chromosomal linkage associated with disease severity in the hydrocephalic H-Tx rat.

摘要: Infantile hydrocephalus results in neurological deficits despite surgical treatment. Fetal-onset humans can be caused by developmental abnormalities that are genetic origin. The H-Tx rat has with 40% penetrance and a polygenic inheritance. A backcross Fisher F344 inbred strain produced total of 1500 progeny 17.5% hydrocephalus. Of these, only 12.3% had overt disease the remaining 5.2% mild seen after fixation brain. Disease severity was measured for all affected rats using ratio ventricle to brain width. measure confirmed there two populations, (M; ratio, 0.4), small overlap. For genotyping, populations were each subdivided based on give four groups increasing severity. After an initial genome scan microsatellite markers, hydrocephalic subset 128 normal genotyped chromosomes 4, 9, 10, 11, 17 19. Rats mildest group association locus chromosome 4 (LOD 2.4), whereas those severest associated 3.2). All except least heterozygous genotype 10 11 4.5 3.5, respectively). Chromosomes 9 19 weak linkage number hydrocephalus-associated loci carried correlated disease. It is concluded influenced different loci.