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A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees.

ABSTRACT: We have completed a genome scan of a 12-generation, 3,400-member pedigree with schizophrenia. Samples from 210 individuals were collected from the pedigree. We performed an "affecteds-only" genome-scan analysis using 43 members of the pedigree. The affected individuals included 29 patients with schizophrenia, 10 with schizoaffective disorders, and 4 with psychosis not otherwise specified. Two sets of white-European allele frequencies were used-one from a Swedish control population (46 unrelated individuals) and one from the pedigree (210 individuals). All analyses pointed to the same region: D6S264, located at 6q25.2, showed a maximum LOD score of 3.45 when allele frequencies in the Swedish control population were used, compared with a maximum LOD score of 2.59 when the pedigree's allele frequencies were used. We analyzed additional markers in the 6q25 region and found a maximum LOD score of 6.6 with marker D6S253, as well as a 6-cM haplotype (markers D6S253-D6S264) that segregated, after 12 generations, with the majority of the affected individuals. Multipoint analysis was performed with the markers in the 6q25 region, and a maximum LOD score of 7.7 was obtained. To evaluate the significance of the genome scan, we simulated the complete analysis under the assumption of no linkage. The results showed that a LOD score >2.2 should be considered as suggestive of linkage, whereas a LOD score >3.7 should be considered as significant. These results suggest that a common ancestral region was inherited by the affected individuals in this large pedigree.

SUBMITTER: Lindholm E

PROVIDER: S-EPMC1226052 | biostudies-literature | 2001 Jul

REPOSITORIES: biostudies-literature

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A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees.

Lindholm E E Ekholm B B Shaw S S Jalonen P P Johansson G G Pettersson U U Sherrington R R Adolfsson R R Jazin E E

American journal of human genetics 20010525 1

We have completed a genome scan of a 12-generation, 3,400-member pedigree with schizophrenia. Samples from 210 individuals were collected from the pedigree. We performed an "affecteds-only" genome-scan analysis using 43 members of the pedigree. The affected individuals included 29 patients with schizophrenia, 10 with schizoaffective disorders, and 4 with psychosis not otherwise specified. Two sets of white-European allele frequencies were used-one from a Swedish control population (46 unrelated ...[more]

PMID: 11389481

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Project description:A primary aim of historical biogeography is to identify the causal factors or processes that have shaped the composition and distribution of biotas over time. Another is to infer the evolution of geographic ranges of species and clades in a phylogenetic context. To this end, historical biogeography addresses important questions such as: Where were ancestors distributed? Where did lineages originate? Which processes cause geographic ranges to evolve through time? Allium subgenus Anguinum comprises approximately twelve taxa with a disjunct distribution in the high mountains from south-western Europe to eastern Asia and in northeastern North America. Although both the systematic position and the geographical limits of Anguinum have been identified, to date no molecular systematic study has been performed utilizing a comprehensive sampling of these species. With an emphasis on the Anguinum eastern Asian geographical group, the goals of the present study were: (i) to infer species-level phylogenetic relationships within Anguinum, (ii) to assess molecular divergence and estimated the times of the major splits in Anguinum and (iii) to trace the biogeographic history of the subgenus. Four DNA sequences (ITS, matK, trnH-psbA, rps16) were used to reconstruct the phylogeny of Allium subgen. Anguinum RbcL sequences were used to estimate divergences time for Allium, and sequences of ITS were used to estimate the divergence times for Anguinum and its main lineages and to provide implications for the evolutionary history of the subgenus. Phylogenetic analyses for all Allium corroborate that Anguinum is monophyletic and indicate that Anguinum is composed of two sister groups: one with a Eurasian-American distribution, and the other restricted to eastern Asia. In the eastern Asian geographical group, incongruence between gene trees and morphology-based taxonomies was recovered as was incongruence between data from plastid and nuclear sequences. This incongruence is likely due to the combined effects of a recent radiation, incomplete lineage sorting, and hybridization/introgression. Divergence time estimates suggest that the crown group of Anguinum originated during the late Miocene (ca. 7.16 Mya) and then diverged and dispersed. Biogeographic analyses using statistical dispersal-vicariance analysis (S-DIVA) and a likelihood method support an eastern Asia origin of Anguinum It is inferred that in the late Pliocene/Early Pleistocene, with cooling climates and the uplift of the Himalayas and Hengduan Mountains, the ancestor of the eastern Asian alliance clade underwent a very recent radiation.

Dataset Information

A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees.

Publications

A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees.

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