Genetic and physical mapping of a type 1 diabetes susceptibility gene (IDDM12) to a 100-kb phagemid artificial chromosome clone containing D2S72-CTLA4-D2S105 on chromosome 2q33.

Polymorphic markers within the CTLA4 gene on chromosome 2q33 have been shown to be associated with type 1 diabetes. Therefore, a gene responsible for the disease (IDDM12) most likely lies within a region of <1-2 cM of CTLA4. To define more precisely the IDDM12 interval, we genotyped a multiethnic (U.S. Caucasian, Mexican-American, French, Spanish, Korean, and Chinese) collection of 178 simplex and 350 multiplex families for 10 polymorphic markers within a genomic interval of approximately 300 kb, which contains the candidate genes CTLA4 and CD28. The order of these markers (D2S346, CD28, GGAA19E07, D2S307, D2S72, CTLA4, D2S105, and GATA52A04) was determined by sequence tagged site content mapping of bacterial artificial chromosome (BAC) and yeast artificial chromosome (YAC) clones. The transmission disequilibrium test (TDT) analyses of our data revealed significant association/linkage with three markers within CTLA4 and two immediate flanking markers (D2S72 and D2S105) on each side of CTLA4 but not with more distant markers including the candidate gene CD28. Tsp analyses revealed significant association only with the three polymorphic markers within the CTLA4 gene. The markers linked and associated with type 1 diabetes are contained within a phagemid artificial chromosome clone of 100 kb, suggesting that the IDDM12 locus is either CTLA4 or an unknown gene in very close proximity.

Effects of supplementation on voluntary forage intake, diet digestibility, and animal performance.

A data base was constructed to describe and estimate supplementation effects in nonlactating cattle consuming forage ad libitum. The data base included 66 publications on 126 forages (73 harvested and 53 grazed) and a total of 444 comparisons between a control, unsupplemented treatment and a supplemented treatment. Daily gains were reported for 301 comparisons and voluntary intake for 258. Direct measures of forage digestibility were reported for 202 comparisons, and total diet digestibility for 150. Supplements did not increase gain in all cases. Change in ADG due to supplement was not related closely to intake of supplemental TDN. Lowest increases in ADG were with native forages supplemented with molasses alone or with low intakes of molasses containing high levels of NPN. Greatest increases in gain were with improved forages, supplements with > 60% TDN, and supplemental CP intake > .05% of BW. Supplements decreased voluntary forage intake (VFI) when supplemental TDN intake was > .7% of BW, forage TDN:CP ratio was < 7 (adequate N), or VFI when fed alone was > 1.75% of BW. When supplements increased VFI, forage TDN: CP ratio was > 7 (N deficit), and VFI when fed alone was often low. There was little relationship between change in VFI and sources of supplemental CP and TDN. Supplements caused total diet TDN concentration to deviate from expected values by -10 to +5% of OM. When supplemental TDN intake was > .7% of BW, diet TDN concentration was always less than expected. There was little relationship between deviation from expected total diet TDN and type or composition of forages or supplements. Empirical multiple regression equations were developed to estimate effects of supplements on VFI and total diet TDN concentration. The most acceptable intake equation estimated VFI when fed with supplement (r2 = .84) That equation included VFI when fed alone, supplement intake, CP and TDN concentrations in forage and supplement, and classification codes describing forages and supplemental energy. The most acceptable equation for estimating total diet TDN concentration included only the expected total diet TDN concentration (r2 = .87). These equations may be used in nutritional models to account for associative effects.