The genome of the yeast Saccharomyces cerevisiae contains a family of genes related to the HSP7O genes (encoding the 70-kDa heat shock protein) of other eukaryotes. Mutations in two of these yeast genes (SSCI and SSDI), whose expression is increased a few fold after temperature upshift, were constructed in vitro and substituted into the yeast genome in place of the wild-type alleles. No phenotypic effects of the mutation in SSDI were detected. However, a functional SSCI gene is essential for vegetative growth. This result, in conjunction with experiments involving mutations in other members of this multigene family, indicates that at least three distinct functions are carried out by genes of the HSP70 family.The 70-kDa heat-inducible protein (HSP70) has been highly conserved in evolution; related proteins have been identified in plants, animals, and bacteria. The bacterium Escherichia coli has a single HSP70-related gene, dnaK, whereas eukaryotes have evolved families of related genes (1, 2). The complexity and number of genes composing the families differ among species. The Drosophila HSP70 family contains at least three genes that are expressed during normal development (3), as well as a single copy of the heat-inducible HSP68 gene and five to six copies of the inducible HSP70 genes (4). The regulation of expression of these related genes in eukaryotes is complex, some being expressed only after a temperature upshift or other stress, while others are expressed under normal growth conditions. The HSP70 multigene family of Saccharomyces cerevisiae contains at least eight genes. These genes, originally named YG10-107, have been renamed, on the basis of structural and functional similarities, SSAJ-4 (stress seventy subfamily A; YGIOO, YG102, YG106, and YG107, respectively), SSBI and -2 (YGIOJ and YG103, respectively); SSCJ (YG104), and SSDI (YG05). The sequence relationship among the members of this family is complex, with nucleotide sequence similarity ranging from about 50% to 96% (5). The expression of the family members is modulated differentially in response to changes in growth temperature. For example, SSA3 and SSA4 are expressed at very low levels during steady-state growth at 23°C, but their expression is greatly enhanced upon an upshift to 37°C (5). Transcripts of SSBI and SSB2 are abundant during steady-state growth but rapidly decrease upon an upshift in temperature (6). Expression of other family members change little or only severalfold after a heat shock.A major question concerning multigene families is whether the members of a family perform identical or distinct functions. In our laboratory, strains containing mutations in members of the HSP70 family have been constructed, in an attempt to determine the number of distinct functions carried out by members of this family. Previous reports (6, 7) described the effects of mutations in four genes of this family. We report here the effects of mutations in two other members of the HSP70 family, one of which (SSCI) is an essential gene. MATERIALS ...

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H ypertension is one of the most important risk factors for cardiovascular diseases. Despite extensive research examining the causes of blood pressure variation, a significant proportion of blood pressure variation is yet to be explained. Studies of families and twins suggest that 20-40% of blood pressure variation can be attributed to genetic factors.1 Evidence shows that the genetic contribution is even greater for young onset hypertension. 2 We feel that genetic approaches focusing on young onset hypertension will provide new insight into the pathogenesis of hypertension.In our previous report, the affected sib pairs (25 independent, affected sib pairs) method showed positive signs of linkage for markers of the atrial natriuretic peptide gene (NPPA) (D1S1612, p=0.0162), angiotensinogen gene (AGT) (D1S547, p=0.0263), lipoprotein lipase gene (LPL) (D8S1145, p=0.0284), and angiotensin converting enzyme gene (DCP1) (D17S2193, p=0.0256), 3 indicating that multiple pathogenic pathways may be involved in the aetiology of young onset hypertension. Owing to this aetiological complexity, in the current study we focus on high resolution mapping of AGT (located on 1q42-43) and DCP1 (located on 17q23), genes of the renin angiotensin system (RAS). Renin catalyses the first step of the activation pathway of angiotensinogen to angiotensin I, which is then cleaved to angiotensin II by angiotensin I converting enzyme. This cascade can lead to aldosterone release, vasoconstriction, and increased blood pressure. Although the RAS has been extensively studied, it remains unclear how and to what extent RAS gene variants contribute to the blood pressure variations in various human populations. MATERIALS AND METHODSWe have recruited 59 nuclear families (a total of 214 subjects) from a hypertension clinic at Taipei Veterans General Hospital, Taiwan. Our study group included 81 young onset hypertensive patients (59 probands and 22 affected sibs, mean age 30.4 (SD 0.95)), 39 normotensive sibs (mean age 32.2 (SD 1.6)), and 94 parents. Our previous study included 25 affected sib pairs from 18 families for affected sib pair analysis. This transmission disequilibrium test (TDT) study used information from all 59 families with probands. Therefore, the former is a subset of the latter. The protocol of this study was approved by the Human Investigation Committee of the Institute of Biomedical Sciences, Academia Sinica.Polymorphic microsatellite markers located on 1q42-43 and 17q23 were selected based on GeneMap'99 and comprehensive human genetic maps from the Marshfield Medical Research Foundation, and obtained from Multi-Colored Fluorescent Human MapPairs Markers of Research Genetics (Huntsville, AL). Nine markers on 1q42-43 were selected: D1S2805 (245.05 cM), D1S3462 (247.23 cM), D1S459 (247.23 cM), D1S1540 (252.12 cM), D1S235 (254.64 cM), D1S517 (262.96 cM), D1S1149 (262.96 cM), D1S1594 (265.49 cM), and D1S547 (267.51 cM). The six markers on 17q23 were D17S1297 (83.40 cM), D17S1295 (83.40 cM), D17S942 (85.94 cM), ATA108a05 (88.76 cM), D17...