Genome-wide linkage analysis of inherited hydrocephalus in the H-Tx rat

Genome-wide linkage analysis of inherited hydrocephalus in the H-Tx rat Inherited hydrocephalus in humans has received very little attention, most probably because known occurrences are sporadic and systematic investigation is difficult. The H-Tx rat, one of a number of rodent strains with inherited hydrocephalus, has a complex inheritance with more than one postulated susceptibility gene and 40% penetrance. The aim of this study was to perform a genome-wide scan on backcross progeny derived from H-Tx and Fisher F344 rats, to identify genomic regions associated with hydrocephalus. Penetrance of hydrocephalus in (H-Tx × F344) F1× H-Tx was 12.3%. All severely hydrocephalic progeny (n = 185) and a subset of normal progeny (n = 128) were screened with 110 simple sequence length polymorphisms (SSLPs) with 83% coverage of the genome. A significant susceptibility locus was found on chromosome (Chr) 11 (LOD = 3.1). Three loci with suggestive linkage were found on Chr 17 (LOD = 2.4), on Chr 9 (LOD = 1.94), and on Chr 19 (LOD = 1.91). For the loci on Chr 11 and 19, hydrocephalus was associated with the heterozygous genotype, while the other two were recessive. Although none of the four loci was essential for the hydrocephalic phenotype, the additive effects of two, three, or four loci increased the penetrance in a linear fashion. Altogether these four loci accounted for 13.5% of the total variance. It is concluded that hydrocephalus in the H-Tx rat is associated with two, possibly four genetic loci, but that there may be additional undefined genetic and environmental influences. Mammalian Genome Springer Journals

Genome-wide linkage analysis of inherited hydrocephalus in the H-Tx rat

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Copyright © 2001 by Springer-Verlag New York Inc.
Life Sciences; Cell Biology; Animal Genetics and Genomics; Human Genetics
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