Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.

L e t f * ( x ) be t h e u s u a l P a r z e n -R o s e n b l a t t k e r n e l e s t i m a t o r n o f t h e p d f f o f a random v a r i a b l e X based on a sample XI , . . . ,X n f r o m X. I n many p r a c t i c a l a p p l i c a t i o n s , i t i s known t h a t X > c a n d / o r X < d f o r g i v e n c o n s t a n t s c and d. A d d i t i o n a l l y , one m i g h t know t h e v a l u e s o f f ( c ) a n d / o r f ( d ) . "mi r r o r image" and " t i e d down" m o d i f i c a t i o n s i n c o r p o r a t e t h i s a d d i t i o n a l i n f o r m a t i o n i n t o f n w h i c h has s u p p o r t [c,d]. T h i s e s t i m a t o r T h i s p a p e r s t u d i e s * o f f n w h i c h an e s t i m a t o r i s i n t e r p r e t e d i n a manner w h i c h a l l o w s one t o use most o f t h e known convergence p r o p e r t i e s o f k e r n e l e s t i m a t e s i n s t u d y i n g t h e b e h a v i o r of fn.

Fly immune response to parasitoids

Expression profiling of the transcriptional response at 9 time points of Drosophila larvae attacked by insect parasites revealed 159 genes that were differentially expressed between parasitized and control larvae. Most genes with altered expression following parasitoid attack had not previously been associated with immune defense.

One approach to understanding common human diseases is to determine the genetic defects responsible for similar diseases in animal models and place those defective genes in their corresponding biochemical pathways. Our laboratory is working with an animal model for human rheumatoid arthritis called collagen-induced arthritis (CIA). We are particularly interested in determining the location of disease-predisposing loci. To that end, we performed experiments to localize susceptibility loci for CIA in an F2 cross between the highly susceptible mouse strain DBA͞1j and the highly resistant mouse strain SWR͞j. Specifically, a quantitative trait locus analysis was performed to localize regions of the mouse genome responsible for susceptibility͞severity to CIA. One susceptibility locus, Cia1 in the major histocompatibility locus, had been identified previously. Two additional loci were detected in our analysis that contribute to CIA severity (Cia2, Cia3) on chromosomes 2 and 6. A third locus was detected that contributes to the age of onset of the disease. This locus (Cia4) was located on chromosome 2 and was linked to the same region as Cia2. Determining the identity of these loci may provide insights into the etiology of human rheumatoid arthritis.