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Content archived on 2024-06-18

Sequence based strategies to identify genetic variation associated with mental retardation and schizophrenia

Objective

Mental retardation (MR) and schizophrenia (SCZ) are disorders of the brain that affect 2-3% and 1% of the population, respectively. Both disorders are considered to be highly heritable, but exhibit heterogeneous genetic etiology. Recent genetic studies have led to discoveries that the same variants that can give rise to different neuropsychiatric disorders, including MR and SCZ. In this proposal, sequencing will be used to identify novel genes involved in MR and SCZ, and to explore the potential overlap between these disorders. The specific goals of the research plan include:
1. Genetic characterization of patients from large pedigrees with SCZ and MR.
Five pedigrees have been collected in which multiple individuals are affected by SCZ or MR. The pedigrees vary in size, with the largest spanning 12 generations including 3,400 individuals. Exome and whole genome sequencing will be performed to identify the genetic variants associated with disease. Candidate genes identified will be screened in large independent cohorts of MR and SCZ patients. In addition, RNA sequencing will be performed on cell lines established for patients and controls from two of the pedigrees.
2. Screening of trios to identify novel genes causing MR
Mental retardation (MR) patients are typically referred for array-based analysis. With current genetic screening using microarray, a clinically significant rearrangement is identified in 15-20% of patients. I propose use high throughput sequencing to screen MR patients and their parents with the goal of identifying new MR genes and to investigate to what extent the diagnostic yield can be increased.

By combining sequencing, bioinformatics and carefully selected clinical material, the work presented in this proposal will lead to an increased understanding of disease mechanisms and enable the development of novel targets and strategies for molecular diagnostic screening.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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ERC-2011-StG_20101109
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Funding Scheme

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ERC-SG - ERC Starting Grant

Host institution

UPPSALA UNIVERSITET
EU contribution
€ 1 496 574,00
Address
VON KRAEMERS ALLE 4
751 05 Uppsala
Sweden

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Region
Östra Sverige Östra Mellansverige Uppsala län
Activity type
Higher or Secondary Education Establishments
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Total cost

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No data

Beneficiaries (1)

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