Schellenberg, Gerard D.; Payami, Haydeh; Wijsman, Ellen M.; Orr, Harry T.; Goddard, Katrina A. B.; Anderson, Leojean; Nemens, Ellen; White, June A.; Alonso, M. Elisa; Ball, Melvyn J.; Kaye, Jeffrey; Morris, John C.; Chui, Helena; Sadovnick, A. Dessa; Hest
Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analyses were used, in 49 families with a mean age at onset ≥60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score ≤ –2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P < .02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52...
Schellenberg, Gerard D.; Pericak-Vance, Margaret A.; Wijsman, Ellen M.; Moore, Deborah K.; Gaskell, Perry C.; Yamaoka, Larry A.; Bebout, Jacqueline L.; Anderson, Leojean; Welsh, Kathleen A.; Clark, Christopher M.; Martin, George M.; Roses, Allen D.; Bird,
Chromosome 21 markers were tested for linkage to familial Alzheimer disease (FAD) in 48 kindreds. These families had multiple cases of Alzheimer disease (AD) in 2 or more generations with family age-at-onset means (M) ranging from 41 to 83 years. Included in this group are seven Volga German families which are thought to be genetically homogeneous with respect to FAD. Autopsy documentation of AD was available for 32 families. Linkage to the 21 q11-q21 region was tested using D21S16, D21S13, D21S110, D21S1/S11, and the APP gene as genetic markers. When linkage results for all the families were summed, the LOD scores for these markers were consistently negative and the entire region was formally excluded. Linkage results were also summed for the following family groups; late-onset (M > 60), early-onset (M ≤ 60), Volga Germans (M = 56), and early-onset non–Volga Germans (M ≤ 60). For the first three groups, LOD scores were negative for this region. For the early-onset non–Volga German group (six families), small positive LOD scores of Zmax = 0.78 (recombination fraction θ = .15), Zmax = 0.27 (θ = .15), and Zmax = 0.64 (θ = .0), were observed for D21S13, D21S16, and D21S110, respectively. The remainder of the long arm of chromosome 21 was tested for linkage to FAD using seven markers spanning the q22 region. Results for these markers were also predominantly negative. Thus it is highly unlikely that a chromosome 21 gene is responsible for late-onset FAD and at least some forms of early-onset FAD represented by the Volga German kindreds.
A large number of familial Alzheimer disease (FAD) kindreds were examined to determine whether mutations in the amyloid precursor protein (APP) gene could be responsible for the disease. Previous studies have identified three mutations at APP codon 717 which are pathogenic for Alzheimer disease (AD). Samples from affected subjects were examined for mutations in exons 16 and 17 of the APP gene. A combination of direct sequencing and single-strand conformational polymorphism analysis was used. Sporadic AD and normal controls were also examined by the same methods. Five sequence variants were identified. One variant at APP codon 693 resulted in a Glu→Gly change. This is the same codon as the hereditary cerebral hemorrhage with amyloidosis–Dutch type Glu→Gln mutation. Another single-base change at APP codon 708 did not alter the amino acid encoded at this site. Two point mutations and a 6-bp deletion were identified in the intronic sequences surrounding exon 17. None of the variants could be unambiguously determined to be responsible for FAD. The larger families were also analyzed by testing for linkage of FAD to a highly polymorphic short tandem repeat marker (D21S210) that is tightly linked to APP. Highly negative LOD scores were obtained for the family groups tested...
Presentamos en este artículo datos sobre la existencia actual de un
ethnic revival entre los descendientes de inmigrantes alemanes del
Volga en la Argentina, entre quienes la conservación de la lengua de
origen, que fue comparativamente prolongada respecto de otros grupos
alóctonos radicados en el país, se halla hoy en clara retracción.
Nos centramos, en particular, en las ‘presentaciones en sociedad’ que
publican en línea las principales asociaciones étnicas de la comunidad,
y sobre esos materiales registramos y analizamos qué se dice de
la lengua propia y qué se consigna en ella. Sobre esa base, iniciamos
indagaciones acerca de cómo se imbrican en ese marco las cuestiones
actitudinales, las políticas lingüísticas comunitarias y los usos del alemán
que se realizan desde la referida posición modélica.; Ethnic revival: linguistic attitudes, policies and uses of the Volga
Germans in Argentina. This article presents data on the current existence
of an ethnic revival among the descendants of the Volga German
immigrants in Argentina, among whom the preservation of the source
language, which was comparatively prolonged with respect other
allochthonous groups residing in the country, is now clearly in retraction.
We especially focus on the ‘presentations in society’ which have
been published online by the community’s main ethnic associations...