TPH2 polymorphisms and expression in Prader-Willi syndrome subjects with differing genetic subtypes
| Autor: | Merlin G. Butler, Rebecca S. Henkhaus, Douglas C. Bittel |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Serotonin
congenital hereditary and neonatal diseases and abnormalities Cognitive Neuroscience Disease Biology Article Pathology and Forensic Medicine TPH2 polymorphisms and expression 03 medical and health sciences Chromosome 15 0302 clinical medicine Genetic subtypes Imprinting (psychology) Gene 030304 developmental biology Genetics 0303 health sciences TPH2 nutritional and metabolic diseases Tryptophan hydroxylase Human genetics nervous system diseases Pediatrics Perinatology and Child Health Neurology (clinical) Prader-Willi syndrome Genomic imprinting 030217 neurology & neurosurgery |
| Zdroj: | Journal of neurodevelopmental disorders |
| ISSN: | 1866-1955 1866-1947 |
| DOI: | 10.1007/s11689-010-9051-6 |
| Popis: | Prader-Willi syndrome (PWS) is a genetic imprinting disease that causes developmental and behavioral disturbances resulting from loss of expression of genes from the paternal chromosome 15q11-q13 region. In about 70% of subjects, this portion of the paternal chromosome is deleted, while 25% have two copies of the maternal chromosome 15, or uniparental maternal disomy (UPD; the remaining subjects have imprinting center defects. There are several documented physical and behavioral differences between the two major PWS genetic subtypes (deletion and UPD) indicating the genetic subtype plays a role in clinical presentation. Serotonin is known to be disturbed in PWS and affects both eating behavior and compulsion, which are reported to be abnormal in PWS. We investigated the tryptophan hydroxylase gene (TPH2), the rate-limiting enzyme in the production of brain serotonin, by analyzing three different TPH2 gene polymorphisms, transcript expression, and correlation with PWS genetic subtype. DNA and RNA from lymphoblastoid cell lines derived from 12 PWS and 12 comparison subjects were used for the determination of genetic subtype, TPH2 polymorphisms and quantitative RT-PCR analysis. A similar frequency of TPH2 polymorphisms was seen in the PWS and comparison subjects with PWS deletion subjects showing increased expression with one or more TPH2 polymorphism. Both PWS deletion and PWS UPD subjects had significantly lower TPH2 expression than control subjects and PWS deletion subjects had significantly lower TPH2 expression compared with PWS UPD subjects. PWS subjects with 15q11-q13 deletions had lower TPH2 expression compared with PWS UPD or control subjects, requiring replication and further studies to identify the cause including identification of disturbed gene interactions resulting from the deletion process. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink