GM17201

GM17201 LCL from B-Lymphocyte

Description:

HUMAN VARIATION PANEL - WHITE PANEL OF 50
HUMAN VARIATION PANEL - WHITE PANEL OF 100 (SET 1)
HUMAN VARIATION PANEL - WHITE PANEL OF 200
HUMAN VARIATION PANEL - EUROPEAN WHITE PANEL OF 24
CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 19; CYP2C19

Affected:

No

Sex:

Male

Age:

25 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Human Variation
Pharmacogenetics
GeT-RM Samples
dbGaP

Alternate IDs

GM00130 [HUMAN VARIATION PANEL - WHITE PANEL OF 50]

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Species

Homo sapiens

Common Name

Human

Remarks

Donor subject has a single bp (G-to-A) mutation in exon 5 of the CYP2C19 gene (CYP2C19*2) which creates an aberrant splice site. The change altered the reading frame of the mRNA starting with amino acid 215 and produced a premature stop codon 20 amino acids downstream, resulting in a truncated, nonfunctional protein. Because of the aberrant splice site, a 40-bp deletion occurred at the beginning of exon 5 (from bp 643 to bp 682), resulting in deletion of amino acids 215 to 227. The truncated protein had 234 amino acids and would be catalytically inactive because it lacked the heme-binding region.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Pharmacogenomics Panel

For pharmacogenetic variants please click here: GeT-RM PGx Search

Gene

CYP2C19

Chromosomal Location

10q23.33

Allelic Variant 1

124020.0001; MEPHENYTOIN 4-HYDROXYLASE POOR METABOLIZER

Identified Mutation

21158G>A ; The principal defect in CYP2C19 responsible for the S-mephenytoin poor metabolizer phenotype was found by de Morais et al. (1994) to be a single bp (G-to-A) mutation in exon 5 which creates an aberrant splice site. The change altered the reading frame of the mRNA starting with amino acid 215 and produced a premature stop codon 20 amino acids downstream, resulting in a truncated, nonfunctional protein. De Morais et al. (1994) demonstrated that 7/10 Caucasian and 10/17 Japanese poor metabolizers were homozygous for this defect. The inheritance of the deficient allele was found to be concordant with that of the PM trait. To determine the nature of the defect, since the genomic sequence of CYP2C19 was not yet known, de Morais et al. (1994) developed primers for the intron 4/exon 5 junction empirically. This involved the use of multiple primers for intron 4 based on the sequence of this region in CYP2C9, a closely related gene that shows 95% similarity to CYP2C19 in the upstream region and several exons, and a specific reverse primer for exon 5 of CYP2C19. Because of the aberrant splice site, a 40-bp deletion occurred at the beginning of exon 5 (from bp 643 to bp 682), resulting in deletion of amino acids 215 to 227. The truncated protein had 234 amino acids and would be catalytically inactive because it lacked the heme-binding region. De Morais et al. (1994) developed a simple PCR-based test for the defective CYP2C19 allele.

Phenotypic Data

Remarks

Publications

Pratt VM, Zehnbauer B, Wilson JA, Baak R, Babic N, Bettinotti M, Buller A, Butz K, Campbell M, Civalier C, El-Badry A, Farkas DH, Lyon E, Mandal S, McKinney J, Muralidharan K, Noll L, Sander T, Shabbeer J, Smith C, Telatar M, Toji L, Vairavan A, Vance C, Weck KE, Wu AH, Yeo KT, Zeller M, and Kalman L., Characterization of 107 Genomic DNA Reference Materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1 J Mol Diagn12(6):835-46 2010

PubMed ID: 20889555

Li L, Fridley B, Kalari K, Jenkins G, Batzler A, Safgren S, Hildebrandt M, Ames M, Schaid D, Wang L, Gemcitabine and Cytosine Arabinoside Cytotoxicity: Association with Lymphoblastoid Cell Expression Cancer research68:7050-7058 2008

PubMed ID: 18757419

Atwal GS, Bond GL, Metsuyanim S, Papa M, Friedman E, Distelman-Menachem T, Ben Asher E, Lancet D, Ross DA, Sninsky J, White TJ, Levine AJ, Yarden R, Haplotype structure and selection of the MDM2 oncogene in humans Proceedings of the National Academy of Sciences of the United States of America104:4524-9 2007

PubMed ID: 17360557

Harris SL, Gil G, Robins H, Hu W, Hirshfield K, Bond E, Bond G, Levine AJ, Detection of functional single-nucleotide polymorphisms that affect apoptosis Proceedings of the National Academy of Sciences of the United States of America102:16297-302 2005

PubMed ID: 16260726

Hinds DA, Stuve LL, Nilsen GB, Halperin E, Eskin E, Ballinger DG, Frazer KA, Cox DR, Whole-genome patterns of common DNA variation in three human populations. Science307(5712):1072-9 2005

PubMed ID: 15718463