+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events



Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events



Bmc Medical Genetics 12: 138



RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. In the present study, we have performed a comprehensive study of our HSCR series evaluating the involvement of both RET rare variants (RVs) and common variants (CVs) in the context of the disease. RET mutational screening was performed by dHPLC and direct sequencing for the identification of RVs. In addition Taqman technology was applied for the genotyping of 3 RET CVs previously associated to HSCR, including a variant lying in an enhancer domain within RET intron 1 (rs2435357). Statistical analyses were performed using the SPSS v.17.0 to analyze the distribution of the variants. Our results confirm the strongest association to HSCR for the "enhancer" variant, and demonstrate a significantly higher impact of it in male versus female patients. Integration of the RET RVs and CVs analysis showed that in 91.66% of cases with both kinds of mutational events, the enhancer allele is in trans with the allele bearing the RET RV. A gender effect exists on both the transmission and distribution of rare coding and common HSCR causing mutations. In addition, these RET CVs and RVs seem to act in a synergistic way leading to HSCR phenotype.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 052269711

Download citation: RISBibTeXText

PMID: 21995290

DOI: 10.1186/1471-2350-12-138


Related references

Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients. Plos One 7(5): E36524, 2012

A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). Plos One 10(11): E0134649, 2016

Contribution of rare and common variants determine complex diseases-Hirschsprung disease as a model. Developmental Biology 382(1): 320-329, 2013

Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients. Journal of Psychiatric Research 44(14): 971-978, 2011

Common polymorphisms rather than rare genetic variants of the Runx2 gene are associated with femoral neck BMD in Spanish women. Journal of Bone and Mineral Metabolism 28(6): 696-705, 2011

Effect of population stratification analysis on false-positive rates for common and rare variants. Bmc Proceedings 5 Suppl 9: S116, 2012

Common variants in CACNA1C and MDD susceptibility: A comprehensive meta-analysis. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 171(6): 896-903, 2017

Update to Terwilliger and Göring's "Gene mapping in the 20th and 21st centuries" (2000): gene mapping when rare variants are common and common variants are rare. Human Biology 81(5-6): 729-733, 2016

A comprehensive analysis of the thermodynamic events involved in ligand-receptor binding using CoRIA and its variants. Journal of Computer-Aided Molecular Design 22(2): 91-104, 2008

A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin. Cancer ChemoTherapy and Pharmacology 69(6): 1557-1565, 2012

RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease. Plos One 9(6): E98957, 2015

A comprehensive meta-analysis of common genetic variants in autism spectrum conditions. Molecular Autism 6: 49, 2015

Pathway analysis approaches for rare and common variants: insights from Genetic Analysis Workshop 18. Genetic Epidemiology 38 Suppl 1: S86-S91, 2014

Population structure analysis using rare and common functional variants. Bmc Proceedings 5 Suppl 9: S8, 2012