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Tissue effect on ge...
Tissue effect on genetic control of transcript isoform variation.
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Kwan, Tony (author)
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- Grundberg, Elin (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Metabolic Bone Diseases
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Koka, Vonda (author)
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Ge, Bing (author)
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Lam, Kevin C L (author)
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Dias, Christel (author)
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- Kindmark, Andreas (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Metabolic Bone Diseases
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- Mallmin, Hans (author)
- Uppsala universitet,Ortopedi
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- Ljunggren, Östen (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Metabolic Bone Diseases
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Rivadeneira, Fernando (author)
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Estrada, Karol (author)
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van Meurs, Joyce B (author)
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Uitterlinden, Andre (author)
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- Karlsson, Magnus (author)
- Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Mellström, Dan, 1945 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa,Institute of Medicine, School of Public Health and Community Medicine
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- Nilsson, Olle (author)
- Uppsala universitet,Ortopedi
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Pastinen, Tomi (author)
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Majewski, Jacek (author)
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(creator_code:org_t)
- 2009-08-14
- 2009
- English.
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 5:8
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Abstract
Subject headings
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- Current genome-wide association studies (GWAS) are moving towards the use of large cohorts of primary cell lines to study a disease of interest and to assign biological relevance to the genetic signals identified. Here, we use a panel of human osteoblasts (HObs) to carry out a transcriptomic survey, similar to recent studies in lymphoblastoid cell lines (LCLs). The distinct nature of HObs and LCLs is reflected by the preferential grouping of cell type-specific genes within biologically and functionally relevant pathways unique to each tissue type. We performed cis-association analysis with SNP genotypes to identify genetic variations of transcript isoforms, and our analysis indicates that differential expression of transcript isoforms in HObs is also partly controlled by cis-regulatory genetic variants. These isoforms are regulated by genetic variants in both a tissue-specific and tissue-independent fashion, and these associations have been confirmed by RT-PCR validation. Our study suggests that multiple transcript isoforms are often present in both tissues and that genetic control may affect the relative expression of one isoform to another, rather than having an all-or-none effect. Examination of the top SNPs from a GWAS of bone mineral density show overlap with probeset associations observed in this study. The top hit corresponding to the FAM118A gene was tested for association studies in two additional clinical studies, revealing a novel transcript isoform variant. Our approach to examining transcriptome variation in multiple tissue types is useful for detecting the proportion of genetic variation common to different cell types and for the identification of cell-specific isoform variants that may be functionally relevant, an important follow-up step for GWAS.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Ortopedi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Orthopaedics (hsv//eng)
Keyword
- Bone Density
- Cell Line
- Gene Expression Regulation
- Genetic Variation
- Genome-Wide Association Study
- methods
- Humans
- Organ Specificity
- Osteoblasts
- chemistry
- metabolism
- Polymorphism
- Single Nucleotide
- Protein Isoforms
- genetics
- Transcription
- Genetic
- MEDICINE
- Orthopaedics
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Kwan, Tony
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Grundberg, Elin
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Koka, Vonda
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Ge, Bing
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Lam, Kevin C L
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Dias, Christel
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show more...
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Kindmark, Andrea ...
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Mallmin, Hans
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Ljunggren, Östen
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Rivadeneira, Fer ...
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Estrada, Karol
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van Meurs, Joyce ...
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Uitterlinden, An ...
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Karlsson, Magnus
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Ohlsson, Claes, ...
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Mellström, Dan, ...
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Nilsson, Olle
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Pastinen, Tomi
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Majewski, Jacek
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Orthopaedics
- Articles in the publication
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PLoS genetics
- By the university
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University of Gothenburg
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Lund University
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Uppsala University