Fine mapping of calcineurin (PPP3CA) gene reveals novel alternative splicing patterns, association of 5'UTR trinucleotide repeat with addiction vulnerability, and differential isoform expression in Alzheimer's disease.

paper Cited Public

Authors: Chiocco, Matthew J; Zhu, Xuguang; Walther, Donna; Pletnikova, Olga; Troncoso, Juan C; Uhl, George R; Liu, Qing-Rong
Year: 2010
Journal: Substance use & misuse
PMID: 20590401
DOI: 10.3109/10826084.2010.482449
PMCID: PMC3031160

#	Section	Preview
0	Introduction	Genome wide association using denser and denser single nucleotide polymorphism (SNP) sets has…
1	Introduction	PPP3CA/calcineruin acts as a calcium-activated heteromeric complex that contains calcium,…
2	Introduction	Calcineurin functions include (a) regulation of presynaptic phosphorylation of dynamin and the PP1…
3	Introduction	Although PPP3CA is thus a strong candidate to play central roles in addiction and memory-associated…
4	Materials and Methods — Substance Abuser and Control Research Subjects	Genomic DNAs came from NIH IRP (NIDA) research volunteers of self-reported European and…
5	Materials and Methods — Human Brain Tissue	Brain tissue from 57 pathologically confirmed AD patients and 20 non-AD “control” individuals…
6	Materials and Methods — Simple Sequence Repeat Genotyping	Simple sequence length polymorphisms were identified throughout the PPP3CA gene by alignment of…
7	Materials and Methods — Simple Sequence Repeat Genotyping	SSLPs were genotyped using PCR amplifications in which one primer of the pair was labeled with…
8	Materials and Methods — Simple Sequence Repeat Genotyping	10 min, 45 cycles of 94°C for 0.5 min, 62°C for 0.5 min, 72°C for 0.75 min, followed by 72°C for…
9	Materials and Methods — Simple Sequence Repeat Genotyping	SNP Genotyping With Taqman Assays. SNPs rs2851060, rs713455, and rs3730251 were genotyped using…
10	Materials and Methods — SNP Genotyping Using Multiplex PCR and SNaPshot Assays	PCR primers (Table S2) were generated using Primer3 software…
11	Materials and Methods — SNP Genotyping Using Multiplex PCR and SNaPshot Assays	units per sample exonuclease and 0.50 U/sample SAP, incubating for 30 min at 37° and incubating for…
12	Materials and Methods — Allele-Specific Expression	cDNA samples from human brain region tissues and genomic samples, both from individuals who were…
13	Materials and Methods — Allele-Specific Expression	cycle of 95°C for 0.25 min, 60°C for 0.25 min, and 95°C for 0.25 min, and was used to degrade…
14	Materials and Methods — Isoform-Specific Expression	PPP3CA isoforms were identified by aligning genomic sequence with human PPP3CA ESTs using Sequencher…
15	Materials and Methods — Genetic Data and Statistical Analyses	GOLD software (http://www.sph.umich.edu/csg/abecasis/GOLD) allowed graphical display of LD between…
16	Results — rs1395475 Genotypes in Individually Genotyped Substance Dependence versus Control Samples	We sought verification of the microarray-based genome scan data that used pooled DNA samples (Liu et…
17	Results — Genomic Assembly and Identification of Novel PPP3CA Variants and Splicing Isoforms	To identify potential functional variants that might contribute to associations with the phenotype,…
18	Results — Genomic Assembly and Identification of Novel PPP3CA Variants and Splicing Isoforms	By aligning 15 exons of PPP3CA gene with ESTs (dbEST: http://www.ncbi.nlm.nih.gov/dbEST/) and…
19	Results — Genomic Assembly and Identification of Novel PPP3CA Variants and Splicing Isoforms	well as amino acids that lie N-terminal to calcineurin's autoinhibitory domain [Figure 2(B)].…

Name	Type
6-FAM	drug
ABI Prism 7900HT Sequence Detection System local	drug
Acute gene regulation local	phenotype
AD brain local	anatomy
addiction	phenotype
AD patients	cohort
AD postmortem brain local	cohort
African American	cohort
African–American local	cohort
African–American cohort local	cohort
African–American poly‑substance abuse cohort local	cohort
African-Americans	cohort
African–American substance dependent samples local	cohort
Aging brain local	anatomy
Agonal state local	phenotype
Alzheimer's disease	phenotype
AmpliTaq Gold DNA polymerase local	drug
AmpliTaq Gold polymerase local	drug
amygdala	anatomy
B allele local	variant
brain	anatomy
calcineurin	drug
calcineurin activity local	phenotype
calcineurin expression local	phenotype
calcineurin isoform activity local	phenotype
calcium	drug
calcium/calmodulin local	drug
calmodulin	drug
caudate nucleus	anatomy
cDNA	drug
cerebellum	anatomy
CNEX1-10 local	variant
CNEX1-10 isoform local	variant
CNEX1-2 local	variant
CNEX1-3 local	variant
CNEX13-14 local	variant
CNEX13-15 local	variant
CNEX1-4 local	variant
CNEX3-12 local	variant
CNEX3-12 isoform local	variant
CNEX9-11 local	variant
control	cohort
cortex	anatomy
D allele	variant
death	phenotype
Developmental overrepresentation local	phenotype
Developmental underrepresentation local	phenotype
disease	phenotype
DNM1	gene
dNTPs	drug
dopamine	drug
drug use scale (DUS) local	phenotype
DSMIII-R dependence local	phenotype
DSMIV dependence local	phenotype
European-American abusers	cohort
European ancestry	cohort
European population	cohort
Exonuclease local	drug
exonuclease (USB) local	drug
FAM-labeled primer local	drug
FAM reporter dye local	drug
full sample	cohort
GAPD local	gene
genomic DNA	drug
glutamate	drug
Gold buffer local	drug
Herculase Hotstart DNA polymerase local	drug
Hi-Di Formamide local	drug
hippocampus	anatomy
hypothalamus	anatomy
illicit drug use	phenotype
illness	phenotype
Invitrogen	drug
leukocytes local	other
Liz-120 Size Standards local	drug
Mapt	gene
medial frontal cortex	anatomy
medial temporal gyrus local	anatomy
memory	phenotype
Memory-associated disorders local	phenotype
messenger RNA	drug
MGB probe local	drug
MgCl2	drug
microsatellite	variant
muscle local	other
NFAT local	gene
non-AD control local	cohort
non-AD control individuals local	cohort
PCR primers	drug
PCR product	drug
peripheral tissues local	cohort
physical abuse	phenotype
polysubstance abuse vulnerability local	phenotype
postmortem brain	anatomy
postmortem brain samples local	cohort
PPP1R1B	gene
PPP3CA	gene
PPP3CA 5′UTR C allele local	variant
PPP3CA 5′UTR D allele local	variant
PPP3CA 5′UTR trinucleotide repeat local	variant
PPP3CA 5′UTR tri-nucleotide repeat (GCC) local	variant
PPP3CA-CNEX1-2 local	variant
PPP3CA-CNEX1-3 local	variant
PPP3CA-CNEX13-14 local	variant
PPP3CA-CNEX13-15 local	variant
PPP3CA-CNEX1-4 local	variant
PPP3CA-CNEX9-11 local	variant
PPP3CA_EX1 local	variant
PPP3CA isoform local	variant
PPP3CA_variation local	variant
PPP3CB local	gene
PPP3CC	gene
PPP3R1 local	gene
PPP3R2 local	gene
putamen	anatomy
reward	phenotype
reward and memory phenotypes local	phenotype
RNA	drug
RNAzolB local	drug
ROX350 local	drug
rs1395475 local	variant
rs2850328 local	variant
rs2851060 local	variant
rs3730251 local	variant
rs713455 local	variant
SAP local	drug
shrimp alkaline phosphatase (SAP, USB) local	drug
Simple sequence length polymorphism local	variant
SNaPshot extension primers local	drug
SNaPshot ready Reaction Mix local	drug
SNP	cohort
spleen local	other
ss68756203 local	variant
ss68756204 local	variant
ss68756205 local	variant
substance abuse	phenotype
Substance abuse vulnerability local	phenotype
substance use	phenotype
substantia nigra	anatomy
SuperScript First strand cDNA synthesis local	drug
TaqMan assay	drug
TaqMan Universal PCR Master Mix	drug
Tel-test local	drug
testis local	other
Trait differences local	phenotype
trinucleotide repeat local	variant
VIC reporter dye local	drug

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